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1.
PLoS One ; 15(7): e0235536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614903

RESUMO

OBJECTIVE: Smoking has previously been associated with inflammatory bowel disease (IBD), but no study has reported on cotinine, an objective, biochemical measure of tobacco use. We aimed at testing the hypothesis that cotinine levels among healthy subjects are associated with an increased risk of developing IBD in later life. DESIGN: We analysed plasma cotinine and evaluated corresponding lifestyle questionnaires that included tobacco habits in subjects (n = 96) who later developed late-onset IBD (70 ulcerative colitis (UC) and 26 Crohn's disease (CD)) and in sex and age-matched controls (n = 191). RESULTS: Patients who later developed IBD had significantly higher plasma cotinine levels compared to controls. In multivariable analysis, higher log-cotinine was associated with a higher risk of developing IBD (OR 1.34 (95% CI 1.01-1.63)). After stratifying for time to diagnosis, the association was only significant in subjects with shorter time (< 5.1 years) to diagnosis (OR 1.45 (1.09-1.92)). The findings were similar for UC- and CD-cases, but did not reach statistical significance in CD-cases. Although plasma cotinine concentrations were higher in snuff users compared to combusted tobacco users, no increase in the risk of IBD and lower risk of developing IBD among subjects with shorter time (< 5.1 years) to diagnosis was seen among snuff users. CONCLUSIONS: Cotinine, a biomarker of tobacco use, is associated with increased risk of developing late-onset IBD in general, and UC in particular. No increased risk among snuff users indicates that other components in combusted tobacco than nicotine may be involved in the pathogenesis of IBD among smokers.


Assuntos
Cotinina/sangue , Doenças Inflamatórias Intestinais/diagnóstico , Fumar/efeitos adversos , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Doença de Crohn/diagnóstico , Doença de Crohn/etiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/etiologia , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Inquéritos e Questionários
2.
Nutrients ; 12(5)2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32429429

RESUMO

Large quantities of protein-rich cod residuals, which are currently discarded, could be utilized for human consumption. Although fish fillet intake is related to beneficial health effects, little is known about the potential health effects of consuming cod residual protein powder. Fifty lean adults were randomized to consume capsules with 8.1 g/day of cod residual protein (Cod-RP) or placebo capsules (Control group) for eight weeks, in this randomized, double-blind study. The intervention was completed by 40 participants. Fasting glucose and insulin concentrations were unaffected by Cod-RP supplementation, whereas plasma concentrations of α-hydroxybutyrate, ß-hydroxybutyrate and acetoacetate all were decreased compared with the Control group. Trimethylamine N-oxide concentration in plasma and urine were increased in the Cod-RP group compared with the Control group. To conclude, the reduction in these potential early markers of impaired glucose metabolism following Cod-RP supplementation may indicate beneficial glucoregulatory effects of cod residual proteins. Trimethylamine N-oxide appears to be an appropriate biomarker of cod residual protein intake in lean adults.

3.
Heart ; 106(14): 1073-1079, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32398245

RESUMO

OBJECTIVES: Oxidised cholesterol metabolites are linked to increased production of the active vitamin A (Vit-A) form and monocyte/macrophage activation, which may be reflected by neopterin, a marker of both interferon-γ-mediated immune activation and coronary artery disease risk. We examined the influence of serum lipid parameters and Vit-A on the risk association between neopterin and incident acute myocardial infarction (AMI). METHODS: We included 4130 patients with suspected stable angina pectoris (SAP), of whom 80% received lipid-lowering treatment with statins. Risk associations between plasma neopterin and AMI are given as HRs per SD increase in log-transformed neopterin. RESULTS: During a median follow-up of 7.5 years, 530 (12.8%) patients experienced an AMI. In age-adjusted and sex-adjusted analysis, plasma neopterin was positively associated with incident AMI (HR (95% CI) per SD: 1.26 (1.17 to 1.35)). However, the estimates were most pronounced in patients with serum low-density lipoprotein cholesterol (LDL-C) or apolipoprotein (apo) B100 below-median (HR (95% CI) per SD: 1.35 (1.24 to 1.48) and 1.42 (1.27 to 1.58), respectively; both pinteraction ≤0.03). We also observed a particularly strong risk association in those with above-median Vit-A (HR (95% CI) per SD: 1.32 (1.21 to 1.44); pinteraction=0.03). The estimates were slightly modified after multivariable adjustment. CONCLUSIONS: In patients with suspected SAP, the majority of whom receiving statin therapy, high plasma neopterin was associated with increased risk of AMI particularly among those with low LDL-C and apoB100 or high Vit-A levels. The particularly strong relationship of plasma neopterin with residual cardiovascular risk in patients with low lipid levels should be further investigated.

4.
Int J Cancer ; 147(7): 1917-1927, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222976

RESUMO

Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73) and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16) and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association.

6.
PLoS One ; 15(1): e0227365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923223

RESUMO

BACKGROUND: Metabolites of the kynurenine pathway (mKP) relate to important aspects of heart failure pathophysiology, such as inflammation, energy-homeostasis, apoptosis, and oxidative stress. We aimed to investigate whether mKP predict mortality in patients with heart failure. METHODS: The study included 202 patients with heart failure (73.8% with coronary artery disease (CAD)), propensity score matched to 384 controls without heart disease, and 807 controls with CAD (71%). All underwent coronary angiography and ventriculography at baseline. Plasma mKP, pyridoxal 5'phosphate (PLP) and CRP were measured at baseline. Case-control differences were assessed by logistic regression and survival by Cox regression, adjusted for age, gender, smoking, diabetes, ejection fraction, PLP, eGFR and CRP. Effect measures are reported per standard deviation increments. RESULTS: Higher plasma levels of kynurenine, 3- hydroxykynurenine (HK), quinolinic acid (QA), the kynurenine-tryptophan-ratio (KTR) and the ratio of HK to xanthurenic acid (HK/XA) were detected in heart failure compared to both control groups. The mortality rate per 1000 person-years was 55.5 in patients with heart failure, 14.6 in controls without heart disease and 22.2 in CAD controls. QA [HR 1.80, p = 0.013], HK [HR 1.77, p = 0.005], HK/XA [HR 1.67, p < 0.001] and KTR [HR 1.55, p = 0.009] were associated with increased mortality in patients with heart failure, while XA [HR 0.68-0.80, p = 0.013-0.037] were associated with lower mortality in all groups. HK and HK/XA had weak associations with increased mortality in CAD-controls. CONCLUSION: Elevated plasma levels of mKP and metabolite ratios are associated with increased mortality, independent of CAD, in patients with heart failure.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Cinurenina/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Humanos , Cinurenina/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
7.
PLoS One ; 15(1): e0227384, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923274

RESUMO

Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.


Assuntos
Aminoácidos/metabolismo , Síndrome de Fadiga Crônica/etiologia , Linfoma/complicações , Vitamina B 6/metabolismo , Adolescente , Adulto , Idoso , Aminoácidos/sangue , Sobreviventes de Câncer , Criança , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/metabolismo , Síndrome de Fadiga Crônica/psicologia , Feminino , Humanos , Inflamação/sangue , Linfoma/metabolismo , Linfoma/psicologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Triptofano/metabolismo , Vitamina B 6/sangue , Adulto Jovem
8.
Int J Cancer ; 146(9): 2394-2405, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

9.
Br J Nutr ; 123(4): 419-427, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31760958

RESUMO

Low serum concentrations of several vitamins have been linked to increased risk of diseases including insulin resistance and type 2 diabetes (T2D). Fish is a good source of several vitamins, and the prevalence of T2D is low in populations with high fish intake. The aim of the present study was to investigate the effects of high fish intake on vitamins in serum from adults in autumn in South-Western Norway at 60° north latitude. In this randomised clinical trial, sixty-three healthy participants with overweight/obesity consumed 750 g/week of either cod (n 22) or salmon (n 22) as five weekly dinners or were instructed to continue their normal eating habits but avoid fish intake (Control group, n 19) for 8 weeks. The estimated vitamin D intake was significantly increased in the Salmon group when compared with the Cod group (P = 6·3 × 10-4) and with the Control group (P = 3·5 × 10-6), with no differences between groups for estimated intake of vitamins A, B1, B2, B3, B6, B9, C and E. Serum 25-hydroxyvitamin D3 concentration was decreased in all groups after 8 weeks; however, the reduction in the Salmon group was significantly smaller compared with the Cod group (P = 0·013) and the Control group (P = 0·0060). Cod and salmon intake did not affect serum concentrations of the other measured vitamins. The findings suggest that 750 g/week of salmon was not sufficient to prevent a decrease in serum 25-hydroxyvitamin D3 in autumn in South-Western Norway in adults with overweight/obesity.

10.
J Infect Dis ; 221(3): 419-427, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31538186

RESUMO

BACKGROUND: While both adipose tissue accumulation and tryptophan metabolism alterations are features of human immunodeficiency virus (HIV) infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH). METHODS: Eight hundred sixty-four PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity C-reactive protein (hs-CRP), and lipids. Regression models were used to test associations in PWH. RESULTS: PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (P < .001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (P = .009) and quinolinic-to-kynurenic acid ratio (P = .006) and lower kynurenic acid concentration (P = .019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (P < .001) and neopterin concentrations (P < .001), while kynurenic acid was associated with lower hs-CRP (P = .025) and neopterin concentrations (P = .034). CONCLUSIONS: In PWH, increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of proinflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection.

11.
Cancer Epidemiol Biomarkers Prev ; 29(1): 127-132, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31685561

RESUMO

BACKGROUND: Cotinine is a metabolite of nicotine. Serum and urinary cotinine are validated biomarkers for cigarette exposure. Their performance for lung cancer risk prediction has not been simultaneously examined in epidemiologic studies. METHODS: A nested case-control study, including 452 incident lung cancer cases and 452 smoking-matched controls in the Shanghai cohort study, was conducted. Mass spectrometry-based methods were used to quantify cotinine in serum and urine samples collected from current smokers at baseline, on average 10 years before cancer diagnosis of cases. Logistic regression was used to estimate ORs, 95% confidence intervals (CI), and AUC ROC for lung cancer associated with higher levels of cotinine. RESULTS: Serum and urinary cotinine levels were significantly higher in lung cancer cases than controls. Compared with the lowest quartile serum cotinine (≤0.40 nmol/mL), the OR of lung cancer for smokers in the highest quartiles (>1.39 nmol/mL) was 5.46 (95% CI, 3.38-8.81). Similarly, the OR was 5.49 (95% CI, 3.39-8.87) for highest (>16.38 nmol/mg creatinine) relative to the lowest quartile of urinary total cotinine (≤4.11 nmol/mg creatinine). A risk prediction model yielded an AUC of 0.72 (95% CI, 0.69-0.75) for serum cotinine and 0.72 (95% CI, 0.69-0.75) for urinary total cotinine combined with smoking history. CONCLUSIONS: Urinary and serum cotinine have the same performance in prediction of lung cancer risk for current smokers. IMPACT: Urinary cotinine is a noninvasive biomarker that can replace serum cotinine in risk prediction of future lung cancer risk for current smokers.

12.
Am J Clin Nutr ; 111(1): 178-186, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557280

RESUMO

BACKGROUND: Vitamin B-6 status is routinely measured as pyridoxal 5'-phosphate (PLP) in plasma. Low concentrations of PLP are associated with rheumatic, cardiovascular, and neoplastic diseases. We have previously shown that vitamin B-6 status affects the kynurenine (Kyn) pathway of tryptophan (Trp) catabolism. OBJECTIVE: This study aimed to comprehensively evaluate the use of Kyns as potential markers of functional vitamin B-6 status across 2 large cohorts. METHODS: We measured circulating concentrations of the first 6 metabolites in the Trp catabolic pathway by LC-MS-MS in the community-based Hordaland Health Study (HUSK; n = 7017) and cardiovascular patient-based Western Norway Coronary Angiography Cohort (WECAC; n = 4161). Cross-sectional and longitudinal associations of plasma PLP with Kyns were estimated using linear and nonlinear regression-based methods. RESULTS: 3'-Hydroxykynurenine (HK), a substrate, and all 4 products formed directly by the PLP-dependent enzymes kynurenine transaminase and kynureninase contributed to the explanation of circulating PLP in multivariable-adjusted regression models. The construct HK:(kynurenic acid + xanthurenic acid + 3'-hydroxyanthranilic acid + anthranilic acid), termed HK ratio (HKr), was related to plasma PLP with standardized regression coefficients (95% CIs) of -0.47 (-0.49, -0.45) and -0.46 (-0.49, -0.43) in HUSK and WECAC, respectively. Across strata of cohort and sex, HKr was 1.3- to 2.7-fold more sensitive, but also 1.7- to 2.9-fold more specific to changes in PLP than a previously proposed marker, HK:xanthurenic acid. Notably, the association was strongest at PLP concentrations < âˆ¼20 nmol/L, a recognized threshold for vitamin B-6 deficiency. Finally, PLP and HKr demonstrated highly sex-specific and corroborating associations with age. CONCLUSIONS: The results demonstrate that by combining 5 metabolites in the Kyn pathway into a simple index, HKr, a sensitive and specific indicator of intracellular vitamin B-6 status is obtained. The data also underscore the merit of evaluating alterations in Kyn metabolism when investigating vitamin B-6 and health.


Assuntos
Doenças Cardiovasculares/sangue , Triptofano/metabolismo , Vitamina B 6/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Fosfato de Piridoxal/sangue , Vitamina B 6/metabolismo
13.
PLoS One ; 14(12): e0226069, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805132

RESUMO

INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of one-carbon metabolism. Previously we have reported effects on plasma concentrations of metabolites along these pathways as well as markers of B-vitamin status in rats following treatment with a pan-PPAR agonist. Here we aimed to investigate the effect on these metabolites after specific activation of the PPARα and PPARγ subtypes. METHODS: For a period of 12 days, Male Wistar rats (n = 20) were randomly allocated to receive treatment with the PPARα agonist WY-14.643 (n = 6), the PPARγ agonist rosiglitazone (n = 6) or placebo (n = 8). The animals were sacrificed under fasting conditions, and plasma concentration of metabolites were determined. Group differences were assessed by one-way ANOVA, and planned comparisons were performed for both active treatment groups towards the control group. RESULTS: Treatment with a PPARα agonist was associated with increased plasma concentrations of most biomarkers, with the most pronounced differences observed for betaine, dimethylglycine, glycine, nicotinamide, methylnicotinamide, pyridoxal and methylmalonic acid. Lower levels were observed for flavin mononucleotide. Fewer associations were observed after treatment with a PPARγ agonist, and the most notable was increased plasma serine. CONCLUSION: Treatment with a PPARα agonist influenced plasma concentration of one-carbon metabolites and markers of B-vitamin status. This confirms previous findings, suggesting specific involvement of PPARα in the regulation of these metabolic pathways as well as the status of closely related B-vitamins.


Assuntos
Carbono/metabolismo , PPAR alfa/agonistas , Pirimidinas/farmacologia , Complexo Vitamínico B/sangue , Animais , Masculino , PPAR gama/agonistas , Ratos , Ratos Wistar , Rosiglitazona/farmacologia , Fatores de Tempo
14.
Int J Tryptophan Res ; 12: 1178646919885637, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798303

RESUMO

Background: The apolipoprotein E ε4 gene variant (APOEε4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain. Aim: To assess whether the presence of at least one APOEε4 allele modifies the association between kynurenines and the cognitive prognosis. Methods: A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia Study of Western Norway. The participants had mild Alzheimer disease and Lewy body dementia. Apolipoprotein E ε4 gene variant allele status was classified as one or more ε4 versus any other. Mini-Mental State Examination (MMSE) was measured at baseline and for 5 consecutive years. Mann-Whitney U tests and linear mixed-effects models were used for statistical analysis. Results: There were no significant differences in serum concentrations of tryptophan and kynurenine according to the presence or absence of APOEε4. High serum concentrations of kynurenic acid, quinolinic acid, and picolinic acid, and a higher kynurenine-to-tryptophan ratio, were all associated with more cognitive decline in patients without APOEε4 compared to those with the APOEε4 allele (P-value of the interactions < .05). Conclusions: Kynurenic acid, quinolinic acid, picolinic acid, and the kynurenine-to-tryptophan ratio were associated with a significant increase in cognitive decline when the APOEε4 variant was absent, whereas there was a relatively less decline when the APOEε4 variant was present.

16.
Int J Tryptophan Res ; 12: 1178646919877883, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632053

RESUMO

Introduction: Circulating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia. Objective: The objective of this study was to assess associations between circulating kynurenines, cognitive prognosis, and neuropsychiatric symptoms. Methods: We measured baseline serum Trp, neopterin, pyridoxal 5'-phosphate (PLP), and 9 kynurenines in 155 patients with mild dementia (90 with Alzheimer's disease, 65 with Lewy body dementia). The ratios between kynurenine and Trp and kynurenic acid (KA) to kynurenine (KKR) were calculated. The Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered at baseline and annually over 5 years. Associations between baseline metabolite concentrations with MMSE and the NPI total score were assessed using a generalized structural equation model (mixed-effects multiprocess model), adjusted for age, sex, current smoking, glomerular filtration rate, and PLP. Post hoc associations between KKRs and individual NPI items were assessed using logistic mixed-effects models. False discovery rate (0.05)-adjusted P values (Q values) are reported. Results: Kynurenine had a nonlinear quadratic relationship with the intercept of the MMSE scores over 5 years (Q < 0.05), but not with the slope of MMSE decline. Kynurenine was associated with a higher NPI total score over time (Q < 0.001). Post hoc, both KKR and KA were associated with more hallucinations (Q < 0.05). Conclusions: Kynurenine has a complex relationship with cognition, where both low and high levels were associated with poor cognitive performance. A higher KKR indicated risk for neuropsychiatric symptoms, especially hallucinations.

17.
Eur J Nutr ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502058

RESUMO

PURPOSE: We hypothesized that biomarkers and dietary factors related to cardiovascular disease risk were associated with serum retinol and evaluated these potential associations in patients with suspected coronary artery disease (CAD). METHODS: We used cross-sectional data from 4116 patients hospitalised for suspected CAD. Dietary data were obtained from a subgroup of 1962 patients using a food frequency questionnaire. Potential biomarkers and dietary factors were explored using linear regression modelling adjusted for age and sex. Regression coefficients and corresponding confidence intervals (CI) are given as  % change in serum retinol per unit change in the predictors. Analyses were performed in the total population and in strata of serum retinol tertiles. RESULTS: In age- and sex-adjusted models, serum creatinine (standardized ß: 0.38, 95% CI [0.35, 0.42]), plasma total cysteine (0.26, [0.23, 0.29]), serum uric acid (0.30, [0.26, 0.33]) and plasma neopterin (0.22, [0.18, 0.25]) were positively associated, whereas plasma serine (- 0.15, [- 0.18, - 0.12]) and serum C-reactive protein (- 0.15, [- 0.18, - 0.12]) were inversely associated with serum retinol. When we included the significant biomarkers in a multivariate model, the model explained 33% of the variability (R2 = 0.33) in serum retinol. The results were similar in the lower and upper tertiles of serum retinol. Weak or no associations were observed for dietary factors. CONCLUSIONS: In patients with suspected CAD, concentrations of creatinine, cysteine and uric acid were positively associated with serum retinol. Future studies should assess whether retinol concentrations are influenced by metabolic alterations in patients at risk of cardiovascular disease.

18.
Br J Nutr ; 122(3): 262-273, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31397239

RESUMO

Kidney function affects amino acid metabolism and vitamin status. The aims of the present study were to investigate urine and plasma concentrations of amino acids as well as plasma vitamin status in rats with impaired renal function (Zucker fa/fa rats) and in rats with normal kidney function (Long-Evans rats), and to explore the effects of salmon intake on these parameters and potential biomarkers of salmon intake in both rat strains. Male rats were fed diets with casein as sole protein source (control diet) or 25 % protein from baked salmon and 75 % casein for 4 weeks. Urine concentrations of markers of renal function and most amino acids and plasma concentrations of most vitamins were higher, and plasma concentrations of several amino acids including arginine, total glutathione and most tryptophan metabolites were lower in Zucker fa/fa rats compared with Long-Evans rats fed the control diet. Concentrations of kidney function markers were lower after salmon intake only in Zucker fa/fa rats. A trend towards lower urine concentrations of amino acids was seen in both rat strains fed the salmon diet, but this was more pronounced in Long-Evans rats and did not reflect the dietary amino acid content. Urine 1-methylhistidine, 3-methylhistidine, trimethylamineoxide and creatine concentrations, and plasma 1-methylhistidine and creatine concentrations were higher after salmon intake in both rat strains. To conclude, concentrations of amino acids in urine and plasma as well as vitamin status were different in Zucker fa/fa and Long-Evans rats, and the effects of salmon intake differed by rat strain for some of these parameters.

19.
Eur J Nutr ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401679

RESUMO

PURPOSE: To identify biomarkers to assess participants' compliance in an intervention study with high intake of cod or salmon, compared to a fish-free diet. METHODS: In this randomised clinical trial, 62 healthy overweight/obese participants consumed 750 g/week of either cod (N = 21) or salmon (N = 22) across 5 weekly dinners, or were instructed to continue their normal eating habits but avoid fish intake (Control group, N = 19) for 8 weeks. RESULTS: After cod intake, serum concentrations of trimethylamine N-oxide (TMAO, p = 0.0043), creatine (p = 0.024) and 1-methylhistidine (1-MeHis, p = 0.014), and urine concentrations (relative to creatinine) of TMAO (p = 2.8 × 10-5), creatine (p = 8.3 × 10-4) and 1-MeHis (p = 0.016) were increased when compared to Control group. After salmon intake, serum concentrations of 1-MeHis (p = 2.0 × 10-6) and creatine (p = 6.1 × 10-4), and urine concentrations (relative to creatinine) of 1-MeHis (p = 4.2 × 10-6) and creatine (p = 4.0 × 10-5) were increased when compared to Control group. Serum and urine concentrations of TMAO were more increased following cod intake compared to salmon intake (p = 0.028 and 2.9 × 10-4, respectively), and serum and urine 1-MeHis concentrations were more increased after salmon intake compared to cod intake (p = 8.7 × 10-5 and 1.2 × 10-4, respectively). Cod and salmon intake did not affect serum and urine concentrations of 3-methylhistidine, and only marginally affected concentrations of free amino acids and amino acid metabolites. CONCLUSION: TMAO measured in serum or urine is a potential biomarker of cod intake, and 1-MeHis measured in serum or urine is a potential biomarker of salmon intake.

20.
Brain Stimul ; 12(5): 1135-1142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31176607

RESUMO

BACKGROUND: Prior studies suggest that activation of the tryptophan catabolism via the kynurenine pathway by proinflammatory cytokines may be involved in the pathophysiology of depression. Electroconvulsive therapy (ECT) is an effective treatment for major depression (MD) with immunomodulation as one of the proposed modes of action. OBJECTIVE: The aim of this study was to investigate serum concentrations of tryptophan and kynurenine pathway metabolites in MD patients and healthy controls, and to explore the effect of ECT on components of the kynurenine pathway. METHODS: The study included 27 moderately to severely depressed patients referred to ECT. Blood samples were collected prior to treatment and after the completed ECT-series. Baseline samples were also collected from 14 healthy, age- and sex-matched controls. Serum concentrations of tryptophan, kynurenine, 3-hydroxykynurenine (HK), kynurenic acid (KA), xanthurenic acid (XA), anthranilic acid (AA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA), picolinic acid (Pic), pyridoxal 5'-phosphat (PLP), riboflavin, neopterin and cotinine were measured. RESULTS: Patients with MD had lower levels of neuroprotective kynurenine-pathway metabolites (KA, XA and Pic) and lower metabolite ratios (KA/Kyn and KA/QA) reflecting reduced neuroprotection compared to controls. The concentration of the inflammatory marker neopterin was increased after ECT, along with Pic and the redox active and immunosuppressive metabolite HAA. CONCLUSION: In this pilot study, we found increased concentrations of inflammatory marker neopterin and putative neuroprotective kynurenine metabolites HAA and Pic in MD patients after ECT. Further research in larger cohorts is required to conclude whether ECT exerts its therapeutic effects via changes in the kynurenine pathway.


Assuntos
Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/métodos , Cinurenina/sangue , Triptofano/sangue , Adulto , Biomarcadores/sangue , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
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