The study of tryptophan metabolite concentrations in blood serum and fecal extracts from obese children

2020 ◽  
Vol 66 (6) ◽  
pp. 494-501
Author(s):  
A.V. Shestopalov ◽  
O.P. Shatova ◽  
A.M. Gaponov ◽  
N.E. Moskaleva ◽  
S.A. Appolonova ◽  
...  
Keyword(s):  
Blood Serum ◽  
Metabolic Activation ◽  
Fold Increase ◽  
Kynurenine Pathway ◽  
Healthy Children ◽  
Obese Children ◽  
Fecal Matter ◽  
Metabolic Coupling ◽  
Tryptophan Metabolites ◽  
Tryptophan Metabolite

We found that changes in the concentrations of tryptophan metabolites in the blood serum and in the intestinal contents are one of the mechanisms for the formation of metabolic coupling in the system "macroorganism-intestinal microbiota", which undergoes significant changes in the development of obesity. Although blood kynurenine remained basically unchanged in obese children we found an increase in some of its serum metabolites: anthranilic, kynurenic and xanthurenic acids. It is noteworthy that in the analysis of fecal matter in obese children, revealed a 2-fold increase in the level of kynurenine while the concentration of kynurenine pathway metabolites corresponded to the level of the group of healthy children. This may indicate the metabolic activation of the microbiota associated with the intestinal mucosa. This is also supported by the absence of statistically significant differences in the concentration of indole in healthy children and in obese children in fecal analyses, and a significant increase in the concentration of indole-3-lactate and indole-3-acetate in the blood serum of obese children.

scholarly journals Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP

2021 ◽  
Vol 22 (12) ◽  
pp. 6320
Author(s):  
Monia Lenzi ◽  
Veronica Cocchi ◽  
Sofia Gasperini ◽  
Raffaella Arfè ◽  
Matteo Marti ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Metabolic Activation ◽  
Fold Increase ◽  
Synthetic Cathinones ◽  
The Other ◽  
Oxygen Species ◽  
Genetic Damage ◽  
Mutagenic Potential ◽  
Tk6 Cells ◽  
Mutagenic Effects

Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35–100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.

scholarly journals Association between rs1421085 and rs9939609 Polymorphisms of Fat Mass and Obesity-Associated Gene with High-Density Lipoprotein Cholesterol and Triglyceride in Obese Turkish Children and Adolescents

2020 ◽  
Author(s):  
Nihal Inandiklioğlu ◽  
Adem Yaşar
Keyword(s):  
High Density Lipoprotein ◽  
Fat Mass ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Healthy Children ◽  
Obese Children ◽  
Fto Gene ◽  
Turkish Children

AbstractSeveral studies have shown that rs9939609 and rs1421085 in fat mass and obesity-associated (FTO) gene rs17782313 and rs12970134 in melanocortin-4 receptor (MC4R) gene influence obesity. In the present study, we aimed to determine association between rs9939609, rs1421085, rs17782313, and rs12970134 polymorphism, and their relation with body mass index (BMI), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and lipid values in obese children. We included 100 newly diagnosed obese children and 100 healthy children. The rs1421085 (CC/CT) (p = 0.019) and rs9939609 (AA/AT) (p = 0.002) polymorphism regions were higher in the obese group. Additionally, we found that both the rs1421085 (CC/CT) and rs9939609 (AA/AT) polymorphism associated with high-density lipoprotein cholesterol (p = 0.011 and p = 0.003) and triglycerides (p = 0.01 and p = 0.004) level, respectively. Further, the rs9939609 and rs1421085 variants of FTO gene associated with HDL-cholesterol and triglycerides levels in obese children; however, updated studies with a large sample size are required to establish strong links with genetic variants and risk factors in childhood obesity.

scholarly journals Exploitation of the IDO Pathway in the Therapy of Rheumatoid Arthritis

2013 ◽  
Vol 6s1 ◽  
pp. IJTR.S11737 ◽  
Author(s):  
Richard O. Williams
Keyword(s):  
Rheumatoid Arthritis ◽  
Anthranilic Acid ◽  
Kynurenine Pathway ◽  
Gene Encoding ◽  
Rate Limiting Step ◽  
Tryptophan Metabolites ◽  
Synthetic Derivative ◽  
Rate Limiting ◽  
Kinetics Of ◽  
Draining Lymph Nodes

Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting step along the kynurenine pathway and is thought to play a key role in immune homeostasis through depletion of tryptophan and accumulation of kynurenines. In this review we summarize recent research into the possibility of harnessing the IDO pathway for the therapy of rheumatoid arthritis. Inhibition of IDO activity, or knockout of the gene encoding IDO, was shown to cause an increase in the severity of collagen-induced arthritis, an animal model of rheumatoid arthritis. The increased severity of disease was associated with elevated numbers of pathogenic Th1 and Th17 cells in the joints and draining lymph nodes. In another study, analysis of the kinetics of expression of downstream kynurenine pathway enzymes during the course of arthritis revealed a potential role for tryptophan metabolites in resolution of arthritis. Furthermore, the therapeutic administration of L-kynurenine or [3,4-dimethoxycinnamonyl]-anthranilic acid (a synthetic derivative of 3-hydroxy-anthranilic acid) significantly reduced both clinical and histological progression of experimental arthritis. These findings raise the possibility of exploiting the IDO pathway for the therapy of autoimmune disease.

scholarly journals The profile of plasma non-esterified fatty acids in children with different terms of type 1 diabetes mellitus

2016 ◽  
Vol 62 (2) ◽  
pp. 206-211 ◽  
Author(s):  
V.A. Akmurzina ◽  
E.E. Petryairina ◽  
S.V. Saveliev ◽  
A.A. Selishcheva
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Plasma Lipids ◽  
Solid Phase ◽  
Fold Increase ◽  
Healthy Children ◽  
Esterified Fatty Acids

Composition and quantitative content of non-esterified fatty acids (NEFA) were investigated in plasma samples of healthy children (12) and children with type 1 diabetes mellitus (DM1) (31) by gas chromatography (GC) after preliminary NEFA solid-phase extraction from plasma lipids. There was a significant (p<0.001) 1.6-fold increase in the total level of NEFA regardless of the disease duration. In the group of DM1 children with the disease period less than 1 year there was an increase in the arachidonic acid (20:4) content (30%) and the oleic acid trans-isomer (18:1) content (82%), and also a decrease in the docosahexaenoic acid (22:6 n3) content (26% ) and the docosapentaenoic acids (22:5 n-6) content (60%). In the group of DM1 children with prolonged course of this disease the altered NEFA levels returned to the normal level

scholarly journals TREATMENT OF LACTASE DEFICIENCY IN CHILDREN’S OBESITY WITH GENOTYPE C/C 13910 OF LACTASE GENE

2019 ◽  
Vol 72 (1) ◽  
pp. 17-21
Author(s):  
Alexandr Ye. Abaturov ◽  
Yuri M. Stepanov ◽  
Anna A. Nikulina
Keyword(s):  
Insulin Resistance ◽  
Healthy Children ◽  
Lactase Deficiency ◽  
Obese Children ◽  
Hydrogen Breath Test ◽  
Lactose Maldigestion ◽  
Group I ◽  
Comparison Groups ◽  
Genotype C ◽  
Lactase Gene

Introduction: Excess lactose in the diet of modern man causes the development of not only lactase deficiency, but it can be a factor that contributes to obesity. The aim: To study associations between obesity and genotype C/C 13910 of lactase gene (LCT) in children, to investigate the effectiveness of treatment using drug exogenous lactase and a low-lactose diet. Materials and methods: genotyping of lactase gene by real-time polymerase chain reaction, determining the level of lactose maldigestion by hydrogen breath test (HBT), estimating the insulin resistance with the HOMA-IR index in 70 obese children and 40 healthy children 6 - 18 years. Obese children with genotype C/C 13910 and lactose maldigestion (n=40) were randomized in two groups: children from group I (n=20) received an exogenous lactase preparation, and children from group II (n=20) - low-lactose diet. Results: in obese children, the genotype C/C 13910 is 2 times more often than in healthy children. Obese children with genotype C/C 13910 have a significantly higher value of HBT (32.8–39.8 ppm) compared to healthy children (p<0.05), and an increased value of the HOMA-IR index. After treatment, there was a significant decrease in HBT and the HOMA-IR index in the two comparison groups. Conclusions: signs of insulin resistance are observed in children with obesity, genotype C/C 13910 and lactose maldigestion. The use of exogenous lactase in the therapy or the administration of a low-lactose diet cause approximately the same decrease in the HOMA-IR index.

scholarly journals Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit

2020 ◽  
Vol 13 ◽  
pp. 117864692093627
Author(s):  
Masatoshi Yamashita
Keyword(s):  
Social Life ◽  
Potential Role ◽  
Memory Function ◽  
Dynamic Change ◽  
Central Fatigue ◽  
Brain Regions ◽  
Kynurenine Pathway ◽  
Treadmill Running ◽  
Brain Functions ◽  
Tryptophan Metabolites

Central fatigue leads to reduced ability to perform mental tasks, disrupted social life, and impaired brain functions from childhood to old age. Regarding the neurochemical mechanism, neuroactive tryptophan metabolites are thought to play key roles in central fatigue. Previous studies have supported the “tryptophan-serotonin enhancement hypothesis” in which tryptophan uptake into extensive brain regions enhances serotonin production in the rat model of exercise-induced fatigue. However, serotonin was transiently released after 30 minutes of treadmill running to exhaustion, but this did not reflect the duration of fatigue. In addition, as the vast majority of tryptophan is metabolized along the kynurenine pathway, possible involvement of the tryptophan-kynurenine pathway in the mechanism of central fatigue induction has been pointed out. More recently, our study demonstrated that uptake of tryptophan and kynurenine derived from the peripheral circulation into the brain enhances kynurenic acid production in rat brain in sleep deprivation–induced central fatigue, but without change in serotonin activity. In particular, dynamic change in glial-neuronal interactive processes within the hypothalamus-hippocampal circuit causes central fatigue. Furthermore, increased tryptophan-kynurenine pathway activity in this circuit causes reduced memory function. This indicates a major potential role for the endogenous tryptophan-kynurenine pathway in central fatigue, which supports the “tryptophan-kynurenine enhancement hypothesis.” Here, we review research on the basic neuronal mechanism underlying central fatigue induced by neuroactive tryptophan metabolites. Notably, these basic findings could contribute to our understanding of latent mental problems associated with central fatigue.

scholarly journals Total Oxidant and Antioxidant Status in Prepubertal Children with Obesity

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Grażyna Rowicka ◽  
Hanna Dyląg ◽  
Jadwiga Ambroszkiewicz ◽  
Agnieszka Riahi ◽  
Halina Weker ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Significant Negative Correlation ◽  
Stress Index ◽  
Healthy Children ◽  
Obese Children ◽  
Free Radical Damage ◽  
Prepubertal Children

Aims. Obesity is accompanied by the formation of oxygen free radicals, whose intensified activity without effective defense mechanisms can lead to oxidative stress and related complications. We evaluated the presence of oxidative stress in obese prepubertal children. Methods. The study included 83 healthy children aged 2–10 years (62 with obesity and 21 nonobese controls). Total oxidant capacity (TOC), total antioxidant capacity (TAC), oxidized low-density lipoprotein (ox-LDL), lipid parameters, glucose, and C-reactive protein (CRP) were measured in serum. Oxidative stress index (OSI) was calculated. Results. Serum TOC concentration was significantly higher (p<0.05) and TAC concentration was lower (p<0.05) in obese children. OSI was higher (p<0.01) in obese subjects compared with controls. CRP levels were normal in all children, but median CRP value was higher (p<0.01) and HDL cholesterol levels were lower (p<0.05) in the obese group. We found a significant negative correlation between TAC and ox-LDL concentrations (r=−0.27, p<0.05) in obese children. Furthermore, obesity duration was positively correlated with TOC level (r=0.32, p<0.05) in this group. Conclusions. Obesity-related oxidative stress already occurs in prepubescence. Early obesity diagnosis and the necessary therapeutic activity implementation is a vital strategy for the prophylaxis of free radical damage and related multiorgan complications.

Potential neurobiological ADHD biomarkers

2016 ◽  
Vol 33 (S1) ◽  
pp. S361-S361
Author(s):  
M. Uzbekov ◽  
E. Misionzhnik
Keyword(s):  
Clinical Status ◽  
Fold Increase ◽  
Kynurenine Pathway ◽  
Hyperkinetic Syndrome ◽  
Acid Ratio ◽  
Hydroxyindoleacetic Acid ◽  
Mao Activity ◽  
Platelet Monoamine Oxidase ◽  
Competing Interest ◽  
Psychostimulant Medication

ObjectivesPathogenetic mechanisms of hyperkinetic syndrome (HKS) or attention deficit hyperactivity disorder (ADHD) are not clear.AimTo elucidate some aspects of monoamine involvement in pathogenesis of disorder and response of monoaminergic systems to psychostimulant medication.MethodsLevels of different monoamines, their metabolites and N-methylnicotinamide (end product of kynurenine pathway) were measured in daily samples of urine from children (7–11 years old) with mild and severe HKS using fluorimetric and chromatographic methods as well as platelet monoamine oxidase (MAO) activity. Thirty children with mild HKS received psychostimulant Sydnocarb 5–15 mg daily for 1–1.5 months (for ethical reasons children with severe HKS were not included in study).ResultsHKS was accompanied by activation of dopaminergic and inhibition of noradrenergic systems. There were found metabolic differences between two forms of HKS. Compared with mild HKS, severe HKS was characterized by significant 2-fold increase of MAO activity and L-dopa, dopamine and adrenaline excretion. After sydnocarb treatment children's clinical status improved along with decrease of excretion of homovanillic, vanillylmandelic and 5-hydroxyindoleacetic acids and increase of N-methylnicotinamide.ConclusionsResults indicate that dopaminergic and noradrenergic systems play important role in pathogenesis of HKS. Clinical improvement of HKS children was accompanied by significant increase of N-methylnicotinamide excretion. It is proposed that increased urine excretion of kynurenine metabolite–N-methylnicotinamide and N-methylnicotinamide/5-hydroxyindoleacetic acid ratio can serve as potential biomarkers for evaluation of efficacy of psychostimulant medication. We hypothesize that kynurenine system plays significant role in pathogenesis of HKS/ADHD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

2017 ◽  
Vol 30 (10) ◽  
Author(s):  
Onur Akın ◽  
İbrahim Eker ◽  
Mutluay Arslan ◽  
Süleyman Tolga Yavuz ◽  
Sevil Akman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Central Nervous System ◽  
Nervous System ◽  
Healthy Children ◽  
Model Assessment ◽  
Obese Children ◽  
Neurocognitive Functions ◽  
The Central Nervous System ◽  
Biochemical Indices ◽  
The Impact

AbstractBackground:Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children.Methods:Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups.Results:Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IR– groups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessment-insulin resistance (HOMA-IR) values. EEGs showed significantly more frequent ‘slowing during hyperventilation’ (SDHs) in obese children than non-obese children.Conclusions:Neurocognitive functions, particularly verbal abilities, were impaired in obese children with IR. An early examination of cognitive functions may help identify and correct such abnormalities in obese children.

scholarly journals Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated fromHuman Infants

2019 ◽  
Vol 7 (9) ◽  
pp. 340 ◽  
Author(s):  
Takuma Sakurai ◽  
Toshitaka Odamaki ◽  
Jin-zhong Xiao
Keyword(s):  
Lactic Acid ◽  
Bifidobacterium Longum ◽  
Bifidobacterium Bifidum ◽  
Microbial Interactions ◽  
Human Infants ◽  
Bifidobacterium Breve ◽  
Tryptophan Metabolites ◽  
Tryptophan Metabolite ◽  
Culture Supernatants ◽  
Indole 3 Acetic Acid

Recent studies have shown that metabolites produced by microbes can be considered as mediators of host-microbial interactions. In this study, we examined the production of tryptophan metabolites by Bifidobacterium strains found in the gastrointestinal tracts of humans and other animals. Indole-3-lactic acid (ILA) was the only tryptophan metabolite produced in bifidobacteria culture supernatants. No others, including indole-3-propionic acid, indole-3-acetic acid, and indole-3-aldehyde, were produced. Strains of bifidobacterial species commonly isolated from the intestines of human infants, such as Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Bifidobacterium bifidum, produced higher levels of ILA than did strains of other species. These results imply that infant-type bifidobacteria might play a specific role in host–microbial cross-talk by producing ILA in human infants.

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