Tryptophan Ratio Research Articles

Estimating the standardised ileal digestible tryptophan requirement of pigs kept under commercial conditions in the immediate post-weaning period

This experiment was conducted to determine the optimum standardised ileal digestible (SID) ratio of tryptophan (Trp) to lysine (Lys; Trp:Lys) for commercially housed pigs fed without a dietary antibiotic, but including pharmacological levels of zinc oxide in the immediate post-weaning period. The hypothesis tested was that pigs would positively respond to an increased SID Trp:Lys ratio with improved performance indices and lower levels of circulating biomarkers indicative of an inflammatory response. Forty-two pens were randomly allocated to 1 of 6 treatment groups with varied levels of calculated dietary SID Trp:Lys ratios (0.16, 0.18, 0.20, 0.22, 0.24 and 0.26). Male to female ratios were 3:4 in treatments with 0.16, 0.20, 0.24 SID Trp:Lys and 4:3 for treatments with 0.18, 0.22 and 0.26 SID Trp:Lys. A total of 2430 pigs (6.3 ± 1.09 kg; weaning occurred between 17–20 days (d) of age) were then allocated to 42 pens according to sex and a visual estimate of weight (medium and heavy). Pigs were weighed as a pen on d 1, 8 and 15. Diets were fed for 2 weeks after weaning. Blood samples were taken on d 5 and d 12, with C-reactive protein (C-RP) levels determined on d 5 and d 12 and haptoglobin and plasma urea (PU) levels determined on d 12. Based on analysed amino acid contents in the diets, calculations were made based on SID coefficients and the SID Trp:Lys ratios in diets 1–6 were corrected to 0.168, 0.182, 0.205, 0.211, 0.234 and 0.253. The greatest average daily gain (ADG) and optimal feed conversion ratio (FCR) during the overall 2-week period after weaning were achieved with pigs fed a diet with 0.234 SID Trp:Lys (P =0.05). Levels of C-RP showed a strong trend whereby pigs fed a SID Trp:Lys ratio of 0.253 had the lowest C-RP values and pigs fed a SID Trp:Lys ratio of 0.234 had the highest C-RP values (P =0.061). No differences were found for plasma levels of PU or haptoglobin (P > 0.05) between ratios, suggesting that pigs in the present trial were not under a significant inflammation challenge. Nevertheless, a dietary ratio of 0.234 SID Trp:Lys was found to optimise both ADG and FCR of weaned pigs.

Plasma based targeted metabolomic analysis reveals alterations of phosphatidylcholines and oxidative stress markers in guinea pig model of allergic asthma

Bronchial asthma is one of the most common, chronic respiratory diseases, characterized by reversible airway obstruction, eosinophil and Th2 infiltration, airway hyperresponsiveness and airway remodelling; with many cells and mediators involved. Metabolomics is a relatively new field in “omics” sciences enabling the identification of metabolome for better diagnostics and studying of diseases phenotype.The aim of this study was to investigate the role of targeted metabolomics study for better understanding of the bronchial asthma pathophysiology and finding potential biomarkers in experimental models of eosinophilic inflammation.Plasma level of 185 metabolites was measured with the AbsoluteIDQ™ p180 kit in guinea pigs with experimentally-induced allergic inflammation (n = 15) compared to naïve non-sensitised and non-challenged controls (n = 18).Of the 185 metabolites identified in plasma, 22 were significantly different and changed in ovalbumin sensitised animals. Plasma level of 13 phosphatidylcholines with saturated and unsaturated long-chain fatty acids, total phosphatidylcholines count, carnitine, symmetric dimethylarginine and its ratio to total unmodified arginine, and kynurenine to tryptophan ratio were found to be decreased, while phospholipase A2 activity indicator, tryptophan, taurine and ratio of methionine sulfoxide to unmodified methionine were found to be increased in sensitised guinea pigs compared to naïve controls.Targeted metabolomic analysis revealed significant differences in plasma metabolome of sensitised guinea pigs. Our observations point to the activation of inflammatory and immune pathways, as well as the involvement of oxidative stress.

Plasma tryptophan and kynurenine in females with temporomandibular disorders and fibromyalgia-An exploratory pilot study.

Both temporomandibular disorders myalgia (TMDM) and fibromyalgia (FM) have been linked to central and peripheral changes in serotonin availability. The precursor of serotonin, tryptophan (TRP), is mainly catabolised via another pathway to produce kynurenine (KYN), but whether changes of this pathway are present in TMDM and FM are still unclear. The aim was to explore blood plasma concentrations of TRP and KYN in TMDM and FM in an attempt to identify novel associations for future research. Plasma of 113 female participants (17 TMDM, 40 FM and 56 healthy pain-free controls) were analysed for TRP and KYN concentrations. The degradation of TRP via the KYN pathway was indicated by the KYN to TRP ratio (KYN/TRP). Pain intensities were assessed with the Graded Chronic Pain Scale (GCPS) and Visual Analogue Scale (VAS). Psychological symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder scale (GAD-7). In TMDM there was a negative correlation between TRP and pain intensity (rs =-0.55 P=.023) and positive correlations between KYN/TRP and pain intensity (rs =0.59 P=.013). In FM, KYN/TRP was negatively correlated with anxiety symptoms (rs =-0.36 P=.022) and a trend towards significantly lower TRP levels was found compared to controls (P=.05). The association between KYN/TRP and pain intensity as well as anxiety ratings in this small exploratory study may indicate that KYN/TRP could be a relevant indicator for symptom severity in TMDM and FM. Further investigations of the KYN pathway in chronic myalgia are warranted.

Plasma neurofilament light chain and amyloid-\u03b2 are associated with the kynurenine pathway metabolites in preclinical Alzheimer\u2019s disease

BackgroundBlood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer’s disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation.MethodsCorrelations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65–90 years, with normal global cognition (Mini-Mental State Examination Score ≥ 26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort.ResultsA positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r = .451, p < .0001). Positive correlations were also observed between NFL and kynurenine (r = .364, p < .0005), kynurenic acid (r = .384, p < .0001), 3-hydroxykynurenine (r = .246, p = .014), anthranilic acid (r = .311, p = .002), and quinolinic acid (r = .296, p = .003). Further, significant associations were observed between plasma Aβ40 and the K/T (r = .375, p < .0005), kynurenine (r = .374, p < .0005), kynurenic acid (r = .352, p < .0005), anthranilic acid (r = .381, p < .0005), and quinolinic acid (r = .352, p < .0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r = .215, p = .034), kynurenic acid (r = .214, p = .035), anthranilic acid (r = .278, p = .006), and quinolinic acid (r = .224, p = .027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status; however, associations between plasma Aβ and KP metabolites were only pronounced in individuals with high NAL while associations in individuals with low NAL were nearly absent.ConclusionsThe current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential.

Amino acid composition of beef obtained fromthe specialized meat cattle

The article presents the study results of the amino acid composition of beef obtained from young Aberdeen-Angus and Hereford breeds. It has been established that meat is a complete amino acid product. At the same time, the protein quality indicator of beef obtained from the young of Aberdeen-Angus and Hereford breeds of the age of 12 months was 5.55 and 5.34, and from the bulls of the age of 18 months - 5.73 and 5.49, the methionine: tryptophan ratio – 1.22 and 1.23. The youngsters of the age of 18 months of the studied breeds have the same content of aspartic acid in meat, it is 2.03 g/100 g. A comparative analysis of the concentration of essential amino acids in beef showed that there was more of valine, histidine(-amino-5-imidazole propionic acid), lysine, threonine and phenylalanine in the bullheads of Hereford, than the peers of Aberdeen-Angus breed by 3.30, 4.26, 1.11, 7.14 (P> 0.05), and 4.76%, respectively. The concentrations of valine, isoleucine, methionine and tryptophan were higher in Aberdeen-Angus than in Hereford by 3.30, 2.50, 2.00 and 2.50%, respectively. Analyzing the study results of beef on the content of replaceable amino acids in bulls of the age of 18 months, the advantage in concentration of alanine, glycine, glutamic acid, serine, tyrosine, cystine was on the side of Aberdeen-Angus breed, the difference with peers of Hereford breed was 6.50 (P> 0.05), 2.25, 8.28 (P> 0.05), 56.72 (P> 0.001), 1.10 and 9.09 (P> 0.05)%, respectively. and the quantity of solid eutectoid inclusions based on electron compound Cu31Sn8.

The distinctive characteristics of the nutrient composition of reindeer meat from the Vorkuta district determined by the conditions of the region of origin

Reindeer meat is an important source of crucial nutrients (protein, fat, minerals) in nutrition of Arctic indigenous people. The authentic meat properties are formed under the influence of many factors, the main of which are the lifetime factors including the region of production and peculiarities of keeping. The regional peculiarities of the reindeer meat composition are quite poorly reflected in the reference books on the chemical composition of food products and in the scientific publications. The aim of the work was to evaluate nutritional value, the level of amino acids, fatty acids, minerals and trace elements of reindeer meat from the Vorkuta district. Material and methods. The objects of the research were the samples of reindeer meat (m. longissimus dorsi) from the Vorkuta district obtained from the highly productive semi-domesticated young reindeers of the Nenets breed. The samples were taken from free-ranging male animals at the age of 8-10 month. The amino acid composition was analyzed by the chromatographic method, the mass fraction of tryptophan by the spectrofluorometrically method, oxyproline by the spectrophotometric method. The content of minerals and trace elements was detected by the flame atomic absorption method. The lipid extraction from the average sample was carried out by the extraction with chloroform/ methanol by the Folch method, the purity of the extracted lipids was controlled by the method of thin layer chromatography. The fatty acid composition was determined the gas chromatographic method. Results and discussions. The indicators of the chemical composition of reindeer meat from the Vorkuta district were established. The content of protein was 23.0%, the content of fat 1.2%. The high content of tryptophan (0.628 g/100 g of the product) was characteristic for this prodact. The ratio of tryptophan to oxyproline was 11.8, which exceeded the values in pork and chicken. The low level of polyunsaturated fatty acids (17.8% of total lipids), in particular linoleic acid (6.9%), was assigned to the special features of the composition of meat under investigation. With that, quite high content of saturated fatty acids (48.6% of total lipids) was observed, which explained increased meat stability to oxidative spoilage during long-term storage and processing. The content of calcium in the reindeer meat from the Vorkuta district was 72.25 mg/kg, potassium - 33.3 g/kg, magnesium - 310.25 mg/kg, iron - 55.54 mg/kg, zinc - 41.89 mg/kg, copper - 4.0 mg/kg. The level of iron, magnesium and copper in this type of meat was significantly higher than the data on reindeer meat presented in the reference literature. Conclusion. The obtained data on the chemical composition of reindeer meat from the Vorkuta district can be a basis for the development of the indicators of its authenticity and in the future can be used for identification in case of the need to confirm species and a region of origin of meat, as well as for solving tasks of formation and promotion of regional brands.

Assessment of neopterin and indoleamine 2,3-dioxygenase activity in patients with seasonal influenza: A pilot study.

BackgroundSeasonal influenza is an important cause of morbidity and mortality worldwide. Immune activation after stimulation with interferon‐gamma leads to increased production of neopterin but also results in increased tryptophan catabolism through indoleamine 2,3‐dioxygenase (IDO). Our pilot study determined neopterin serum levels and IDO activity in patients with influenza infection and investigated whether neopterin is linked to clinical outcome parameters (mortality ≤30 days, acute cardiac events (ACE) length of hospitalization, ICU admission).MethodsNeopterin concentrations were analyzed in serum samples of 40 patients with a confirmed diagnosis of influenza infection and in‐hospital treatment for >24 hours. Data were compared to values of 100 healthy blood donors and 48 age‐matched pneumonia patients. In a subgroup of 14 patients, tryptophan and kynurenine concentrations, as well as kynurenine‐to‐tryptophan ratio, were analyzed.ResultsIn all influenza patients, neopterin concentrations were increased and significantly higher compared to those determined in patients with pneumonia and healthy controls. Positive correlations between the duration of hospitalization and neopterin were found. Significantly higher levels of kynurenine, kynurenine‐to‐tryptophan ratio, and lower levels of tryptophan were seen in influenza patients compared to healthy controls.ConclusionsNeopterin seems to be related to the course of the disease and could be a valuable biomarker to identify patients at an elevated risk of a worsened outcome; however, further prospective validation studies are needed to support the here presented preliminary results.

РЕЗУЛЬТАТЫ СКРИНИНГОВОЙ ОЦЕНКИ ПИЩЕВОЙ ЦЕННОСТИ И СОДЕРЖАНИЯ АМИНОКИСЛОТ В РАЦИОНАХ ПИТАНИЯ РАБОЧИХ

To decrease the toxic effects of xenobiotics on healthy workers in healthful and dietary meals, it’s important to consider not only the proper diet intake of macro- and micronutrients, but protein quality in terms of essential amino acids. A study was conducted to evaluate nutritional value and amino acids content in the industrial workers diets of two metallurgical enterprises by calculation and laboratory methods. We found that set of healthful and dietary meals at the calculation stage do not comply with regulatory requirements for fats and carbohydrates by 34 and 16 percent, respectively. According to laboratory tests, from 57 to 68 percent of sets of healthful and dietary meals do not comply with regulatory requirements for proteins, fats and carbohydrates. The discrepancy in the data on the amount of determined nutrients between the calculated and laboratory methods may be due to calculation errors, shortage and quality of raw materials, as well as a limitation of methods for determining fat and carbohydrates. With a set of healthful and dietary meals workers can satisfy the almost daily requirement for the corresponding energy expenditures for some amino acids, however, the required amount of these amino acids in workers in contact with heavy metals has not been established. It has also been found that in diets of healthful and dietary meals, the ratio of tryptophan / lysine / methionine + cystine is violated towards an excess of tryptophan, whose deamination products are highly toxic. It is necessary to continue further investigation of ready-made diets of healthful and dietary meals for nutritional value and amino acid content in order to identify factors affecting the discrepancy within research results between calculation and laboratory methods, as well as establish adequate norms for amino acids intake in workers exposed to toxic substances.

Elevated indoleamine-2,3-dioxygenase enzyme activity in a novel mouse model of HIV-associated atherosclerosis.

HIV atherosclerosis and cardiovascular disease (CVD) represent a significant human health burden in the era of combination antiretroviral therapy (cART). The pathogenesis of HIV atherosclerosis is still poorly understood, due, in part, to the lack of a suitable small animal model. Indoleamine-2,3-dioxygenase (IDO) enzyme activity is the first and rate-limiting step in tryptophan catabolism and is measured by the kynurenine to tryptophan ratio (KTR). The serum KTR is a biomarker of inflammation and has recently been implicated as an important risk factor for CVD in patients living with HIV (PLWH) who are virologically suppressed under cART. However, IDO activity in HIV-associated CVD has not been studied in mouse model before. A novel mouse model of HIV atherosclerosis (Tg26/ApoE) was generated and examined for IDO activity and atherogenesis throughout 8 weeks on a high-fat diet. Tg26/ApoE mice were compared with Tg26 and ApoE single transgenic mice, before and during a high-fat diet. Serum kynurenine, tryptophan and percentage of aortic plaque formation were measured. Additionally, levels of relevant cytokines were investigated in Tg26/ApoE and ApoE. Tg26/ApoE developed an accelerated atherosclerosis with increasing levels of KTR that were associated with plaque progression. This accelerated plaque was potentially driven by elevated levels of circulating IL-6. These results indicate that Tg26/ApoE serve as a new mouse model for HIV-induced atherogenesis, and aid in understanding the role of tryptophan catabolism in the pathogenesis of HIV atherosclerosis/CVD.

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).

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.

Abstract 4993: The Kynurenine Pathway as a possible resistance mechanism to immunotherapy in sarcomas

Abstract Background: Sarcomas are heterogenous malignant mesenchymal neoplasms known to be particularly resistant to immunotherapy, which thus calls the interest of the elucidation of related resistance mechanisms. We recently demonstrated an increase in Kynurenine Pathway (KP) activity in the plasma of patients undergoing Pembrolizumab and metronomic cyclophosphamide. The KP has already been described to favor tolerance and immune escape through the degradation of L-Tryptophan and production of a series of metabolites including L-Kynurenine. While Indoleamine 2,3 dioxygenase (IDO1), a first rate-limiting enzyme of the KP still represents an attractive therapeutic target, the exact functional role of the KP upon immunotherapy has not yet been clearly elucidated. Methods: Using a preclinical syngeneic mouse model of sarcoma based on the inoculation of murine sarcoma MCA205 cell line, we investigated the modulation of the KP upon PDL1 blockade. Besides the evaluation of tumor growth and survival, intratumoral biopsy was performed and used for further gene expression analysis by RT-qPCR. More precisely, KP enzymes- and key cytokines-encoding genes were assessed. Using the same experimental setting on satellite mice, intratumoral microdialysis was performed on day 13 post-tumor inoculation and kynurenine contents were quantified within the tumoral microenvironment. Results: PDL1 blockade, using a specific anti-PDL1 antibody (provided by Genentech), exhibited a clear anti-tumoral effect associated with an intratumoral inflammatory cytokines signature driven by Ifng, Tnfa and Il2. Interestingly, Ifng level was significantly and positively associated with response to anti-PDL1. As regards to KP enzymes, a slight upregulation of the tryptophan-degrading enzymes Ido1 and Ido2 was detected while no changes were observed for Tdo2. An increase of kynurenine-degrading enzymes, including Kmo (encoding for Kynurenine monoamine oxygenase) and Kynu (encoding for kynureninase), was also detected thereby suggesting that PDL1 blockade favors Kynurenine degradation as a possible compensatory mechanism. These results were confirmed by intratumoral microdialysis in the satellite study. Indeed, anti-PDL1 was able to decrease the Kynurenine to Tryptophan ratio(Kyn / Trp) while increasing intratumoral production of kynurenines catabolites. In conclusion, this new set of data on a preclinical sarcoma model highlights for the first time that PDL1 blockade deeply modulates the Kynurenine Pathway with an effect not exclusively associated to the upper part of the pathway and thus warrants further investigation. Citation Format: Imane Nafia, Ariel Savina, Alban Bessede, Antoine ITALIANO. The Kynurenine Pathway as a possible resistance mechanism to immunotherapy in sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4993.

High Kynurenine:Tryptophan Ratio Is Associated With Liver Fibrosis in HIV-Monoinfected and HIV/Hepatitis C Virus-Coinfected Women.

BackgroundTryptophan catabolism, measured by the kynurenine:tryptophan (kyn/trp) ratio, is associated with gut microbiota alterations in people with HIV (PWH). We examined the association of the kyn/trp ratio with liver fibrosis in women with/without HIV infection.MethodsThe plasma kyn/trp ratio was measured in 137 HIV-monoinfected, HIV/hepatitis C virus (HCV)–coinfected, and uninfected women in the Women’s Interagency HIV Study. Fibrosis was estimated using FIB-4 in all participants and vibration-controlled transient elastography liver stiffness measurement (LSM) in a subset (n = 83). We used multivariable linear regression to evaluate the associations of infection status and kyn/trp ratio with relative differences in fibrosis estimates.ResultsThe median kyn/trp ratio (interquartile range) was 0.056 (0.045–0.066) in HIV/HCV-coinfected, 0.038 (0.032–0.046) in HIV-monoinfected, and 0.031 (0.025–0.034) in uninfected women (P < .001). After adjustment for sociodemographic, lifestyle, and metabolic factors, HIV monoinfection and HIV/HCV coinfection were associated with 37% (95% confidence interval [CI], 9% to 73%) and 164% (95% CI, 100% to 250%) greater FIB-4, respectively. When kyn/trp ratio was included, higher kyn/trp ratio was associated with greater FIB-4 (27% per kyn/trp doubling; 95% CI, 5% to 53%), and the associations of HIV monoinfection (29% per kyn/trp doubling; 95% CI, 2% to 63%) and HIV/HCV coinfection (123% per kyn/trp doubling; 95% CI, 63% to 203%) with greater FIB-4 were attenuated. Among those with LSM, higher kyn/trp ratio was associated with greater LSM (43% per kyn/trp doubling; 95% CI, 15% to 79%) in multivariable analysis.ConclusionsThe kyn/trp ratio is elevated in PWH and is associated with greater liver fibrosis. Tryptophan catabolism may modify the relationships between HIV, HCV, and fibrosis.

Impact of Preventive and Therapeutic Zinc Supplements on Citrulline Concentration and the kynurenine: tryptophan Ratio Among Lao Children: A Randomized Controlled Trial (OR07-02-19)

ObjectivesTo investigate the impact of different forms of zinc supplementation on plasma citrulline (CIT), kynurenine (KYN) and tryptophan (TRP) concentrations and the kynurenine: tryptophan ratio (KTR), considered as markers of intestinal function and systemic inflammatory response, among young Lao children. MethodsIn a randomized controlled double-blind trial, 3407 children aged 6–23 mo were randomized into one of four groups and followed for ∼36 weeks: daily preventive zinc dispersible tablet (7 mg zinc; PZ), daily multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP), therapeutic zinc supplements for the treatment of diarrhea (20 mg/d for 10 days with each diarrhea episode; TZ), or daily placebo powder (Control). Plasma samples at baseline and endline for 359 children participating in the parent trial were analyzed at the NIH West Coast Metabolomics Center (UC Davis); plasma CIT, KYN and TRP concentrations were determined by hydrophilic interaction chromatography (HILIC) quadrupole time of flight mass spectrometer (QTOF) tandem mass spectrometry (MS/MS). Linear regression models were used to assess the treatment effect, controlling for baseline value, child age and district. ResultsThe parent trial found no overall group-wise effects on linear growth or diarrhea outcomes. In the subgroup included in the present analyses, mean age at enrollment was 16.0 ± 4.9 mo, 37% were stunted and 83% were zinc deficient. At baseline, mean plasma CIT, KYN and TRP concentrations were 24.6 ± 5.4 μM, 3.27 ± 0.83 μM and 72.3 ± 12.9 μM, respectively; the mean KT ratio was 0.046 ± 0.013. 5% of children had low CIT (< 17 μM) and no children had low TRP (< 35 μM). At endline, there were no differences among intervention groups in mean plasma CIT (25.0–26.6 μM, P = 0.287), KYN (2.96–3.11 μM, P = 0.115), TRP (66.1–70.0 μM, P = 0.151) or the KTR (0.046–0.047, P = 0.981). ConclusionsIn this population, PZ, MNP and TZ had no overall effect on plasma concentrations of CIT, KYN, TRP and the KTR. We plan to further explore if these markers of intestinal function were predictive of subsequent linear growth, or modified the growth response to supplementation. Funding SourcesThe Bill & Melinda Gates Foundation, Nutrition International and the Mathile Institute for the Advancement of Human Nutrition.

Su1080 – High Kynurenine:Tryptophan Ratio is Associated with Liver Fibrosis in Hiv Infection

Su1080 – High Kynurenine:Tryptophan Ratio is Associated with Liver Fibrosis in Hiv Infection

Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia

The kynurenine pathway (KP) of tryptophan (TRP) catabolism links immune system activation with neurotransmitter signaling. The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia. We tested the extent to which: (1) brain KP enzyme mRNAs, (2) brain KP metabolites, and (3) plasma KP metabolites differed on the basis of elevated cytokines in schizophrenia vs. control groups and the extent to which plasma KP metabolites were associated with cognition and brain volume in patients displaying elevated peripheral cytokines. KP enzyme mRNAs and metabolites were assayed in two independent postmortem brain samples from a total of 71 patients with schizophrenia and 72 controls. Plasma KP metabolites, cognition, and brain volumes were measured in an independent cohort of 96 patients with schizophrenia and 81 healthy controls. Groups were stratified based on elevated vs. normal proinflammatory cytokine mRNA levels. In the prefrontal cortex (PFC), kynurenine (KYN)/TRP ratio, KYNA levels, and mRNA for enzymes, tryptophan dioxygenase (TDO) and kynurenine aminotransferases (KATI/II), were significantly increased in the high cytokine schizophrenia subgroup. KAT mRNAs significantly correlated with mRNA for glial fibrillary acidic protein in patients. In plasma, the high cytokine schizophrenia subgroup displayed an elevated KYN/TRP ratio, which correlated inversely with attention and dorsolateral prefrontal cortex (DLPFC) volume. This study provides further evidence for the role of inflammation in a subgroup of patients with schizophrenia and suggests a molecular mechanism through which inflammation could lead to schizophrenia. Proinflammatory cytokines may elicit conversion of TRP to KYN in the periphery and increase the N-methyl-d-aspartate receptor antagonist KYNA via increased KAT mRNA and possibly more enzyme synthesis activity in brain astrocytes, leading to DLPFC volume loss, and attention impairment in schizophrenia.

Показники продуктів забою бичків залежно від селеновмісних добавок у раціоні

The results of researches of products of slaughter of Simmental bream bulls for various selenium-containing additives in the diet are presented. Determination of the morphological composition of carcasses has shown the advantages of experimental groups of animals before the control of the high content of pulp in the carcass (6.1-8.2 kg) and a slightly higher ratio of meat (0.05-0.08). In the carcasses of experimental bulls, bone content decreased (18.7-18.9% versus 20.1% in control). It should be noted that the best results from meat productivity were obtained in the group of animals fed with the diethylvanic preparation Devivit in the diet. In samples of meat of bulls of experimental groups, it was unambiguous, although biometric and unreliable (P>0.05), it was less on 0,28-0,55% of water (76,41-76,14 against 76,69%), and more on the same amount of dry matter. The introduction of selenium supplements in the diet of bulls of the 1st and 2nd experimental groups resulted in an increase compared with the control of muscle protein content by 2.9 and 4.4 absolute percent (P>0.05), while the concentration of fat in this case, on the contrary, fell by 14 and 17.1% respectively (P>0.05). The level of tryptophan in the animal meat of experimental groups was higher than control at 2.29-4.4 mg%, and oxyproline, which reflects the worst grades of meat, on the contrary, was less on 1.31-4.25 mg%. As a result, the protein-quality index (the ratio of tryptophan to oxyproline) in experimental samples of meat was different from the control at 0.2-0.5. At tasting meat estimation on qualitative indices of broth on a 3-point system, no significant difference between groups was found. However, the tasting score of boiled meat of bulls of experimental groups, which was conducted on a 5-point system, averaged 4.35, and controls - 4.17 points, which is 4.1% less than the evaluation of samples of meat experimental animals. There is a probable increase in the activity of aminotransferases in liver tissues - 2.28 ± 0.04 (p<0.05), as well as soluble protein in muscle tissues - 58.39 ± 2.33 (p<0.05) and 114, 76 ± 5,13 liver (p <0,01) of experimental bulls. According to the results of studies of some trace elements in the tissues of the longest muscle of the back, liver and heart of the bulls, no significant differences were observed between the control and experimental animals. In the fattening young, the selenium content in the oblong muscle of the back fluctuated within 0,042 (control) -0,087 mg / kg, which is completely acceptable and safe. From this it can be concluded that beef can be one of the sources of replenishment of the lack of selenium in the human diet. When comparing experimental animals with serum selenium control after 3 months after the start of the experiment, they exceeded the control at 0.031-0.047 μg / ml or 39.2-75.9%. And after 6 months the excess was already 0,033-0,067 μg / ml, or 38,8-58,7%.

Neopterin Levels and Indoleamine 2,3-Dioxygenase Activity as Biomarkers of Immune System Activation and Childhood Allergic Diseases.

BackgroundAlthough Th2 immune activation is predominant in allergic diseases, neopterinlevels and indoleamine 2,3-dioxygenase (IDO)-1 activity (kynurenine:tryptophan ratio), which reflect Th1 immune activity, increase with interferon-gamma (IFN-γ) stimulation. We investigated neopterin, tryptophan, and kynurenine levels as biomarkersof the Th1 immune system activation and changes in IDO-1 activityin children with asthma, allergic rhinitis, and atopic dermatitis, as well as the relationship between these biomarkers and the total IgE level, age, and disease severity.MethodsWe divided 205 children (80 girls and 125 boys, four months to 17 years old) into four groups: controls, patients with asthma, patients with allergic rhinitis, and patients with atopic dermatitis. Peripheral venous blood samples were collected. Neopterin levels were determined by an enzyme immunoassay. Tryptophan and kynurenine levels were analyzed using HPLC. IDO-1 enzyme activity was calculated using tryptophan and kynurenine levels. IgE levels were measured. The Mann-Whitney U test, Kruskal-Wallis test, and Conover post-hoc method were used for statistical analysis.ResultsNeopterin, tryptophan, and kynurenine levels were higher and IgE levels and IDO-1 enzyme activity were lower in patients with asthma and allergic rhinitis than in controls (P<0.05). Patients with atopic dermatitis showed higher neopterin, tryptophan, and kynurenine levels, higher IDO-1 activity, and lower IgE levels thancontrols (P<0.05).ConclusionsThe Th1/Th2 balance is disrupted in children with allergic diseases, concomitant with increased Th1-mediated immune response activation and reduced IgEproduction, which is promoted by Th2-type cytokines.

The Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal.

The plasma kynurenine to tryptophan ([Kyn]/[Trp]) ratio is frequently used to express or reflect the activity of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase (IDO). This ratio is increasingly used instead of measurement of IDO activity, which is often low or undetectable in immune and other cells under basal conditions, but is greatly enhanced after immune activation. The use of this ratio is valid in in vitro studies, eg, in cell cultures or isolated organs, but its ‘blanket’ use in in vivo situations is not, because of modulating factors, such as supply of nutrients; the presence of multiple cell types; complex structural and functional tissue arrangements; the extracellular matrix; and hormonal, cytokine, and paracrine interactions. Determinants other than IDO may therefore be involved in vivo. These are hepatic tryptophan 2,3-dioxygenase (TDO) activity and the flux of plasma-free Trp down the Kyn pathway. In addition, conditions leading to accumulation of Kyn, eg, inhibition of activities of Kyn monooxygenase and kynureninase, could lead to elevation of the aforementioned ratio. In this review, the origin of use of this ratio will be discussed, variations in extent of its elevation will be described, evidence against its indiscriminate use will be presented, and examining determinants other than IDO activity and their correlates will be proposed for future studies.

An exploratory study of neopterin and kynurenine pathway in pterygium

Abstract Pterygium is an inflammatory, vascular and degenerative disorder with unknown aetiology. The aim of this study was to evaluate the changes in neopterin levels, reflecting T-cell immunity, and the kynurenine pathway, the main degradation process of tryptophan, in pterygium. For this purpose, neopterin concentrations were measured in serum and tear samples by enzyme-linked immunosorbent assay (ELISA) in pterygium patients (n=31) and control group (n=32). Kynurenine (KYN) and tryptophan (TRP) serum levels were simultaneously determined by high-performance liquid chromatography (HPLC) for evaluation of the kynurenine pathway. Serum neopterin concentrations and kynurenine to tryptophan ratio (KYN/TRP) as an index of tryptophan breakdown were found increased in pterygium compared to controls (p&lt;0.05). Although there was a 3-fold difference observed between serum and tear neopterin levels, no significant relationship was found. It can be concluded that neopterin may be used as a nonspecific biomarker that reflects immunological activity in pterygium and has clinical potential for evaluation of pterygium pathogenesis. These immune- or inflammatory-mediated changes were also supported by an increased KYN/TRP ratio in pterygium patients.

Effect of carbohydrate ingestion on central fatigue during prolonged running exercise in moderate hypoxia

To determine whether acute exposure to moderate hypoxia alters central and peripheral fatigue and to test whether carbohydrate ingestion impacts fatigue characteristics, 12 trained runners completed three running trials lasting 1 h each at 65% of normoxic maximum oxygen uptake. The first trial was performed in normoxia [inspired O2 fraction ( ) = 0.21], and the last two trials were completed in hypoxia ( = 0.15). Participants ingested a placebo drink in normoxia (NORM-PLA), a placebo drink in hypoxia (HYP-PLA), or a carbohydrate solution in hypoxia (HYP-CHO). HYP conditions were randomized. Peripheral [change in potentiated quadriceps twitch force (ΔQtw,pot)] and central [change in voluntary activation (ΔVA)] fatigue were assessed via preexercise-to-postexercise changes in magnetically evoked quadriceps twitch. In HYP, blood was drawn to determine the ratio of free-tryptophan (f-TRP) to branched-chain amino acids (BCAA). After exercise, peripheral fatigue was reduced to a similar degree in normoxia and hypoxia (ΔQtw,pot = -4.5 ± 1.3% and -4.0 ± 1.5% in NORM-PLA and HYP-PLA, respectively; P = 0.61). Central fatigue was present after normoxic and hypoxic exercise but to a greater degree in HYP-PLA compared with NORM-PLA (ΔVA: -4.7 ± 0.9% vs. -1.9 ± 0.7%; P < 0.01). Carbohydrate ingestion did not influence central fatigue (ΔVA in HYP-CHO: -5.7 ± 1.2%; P = 0.51 vs. HYP-PLA). After exercise, no differences were observed in the ratio of f-TRP to BCAA between HYP-PLA and HYP-CHO ( P = 0.67). Central fatigue increased during prolonged running exercise in moderate hypoxia although the ratio of f-TRP to BCAA remained unchanged. Ingesting carbohydrates while running in hypoxia did not influence fatigue development. NEW & NOTEWORTHY Hypoxic exposure influences the origin of exercise-induced fatigue and the rate of fatigue development depending on the severity of hypoxia. Our data suggest that moderate hypoxia increases central, but not peripheral, fatigue in trained runners exercising at 65% of normoxic maximum oxygen uptake. The increase in central fatigue was unaffected by carbohydrate intake and occurred although the ratio of free tryptophan to branched-chain amino acids remained unchanged.