Amino Acids In Patients Research Articles

A whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer.

Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. Here, we investigated the impact of a whole food, plant-based diet on lowering the serum levels of amino acids in patients with cancer. Patients with metastatic breast cancer (n=18) were enrolled in clinical trial NCT03045289 . An ad libitum whole food, plant-based diet was implemented for 8 weeks without calorie or portion restriction. We found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF-1 were reduced in participants. The diet contained lower levels of essential and non-essential amino acids. Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids). These findings provide a tractable approach to limiting amino acid levels in cancer patients. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities.

Study on the difference and clinical value of serum amino acids in patients with laryngeal squamous cell carcinoma

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry（HPLC-MS） was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group（P<0.05）. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group（P=0.024）. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ（P=0.026）. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma（P=0.041）. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old（P=0.033）. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history（P=0.033）. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption（P=0.003）. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma（AUC=0.855）. However, citrulline alone had the highest specificity（0.830） in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group（P<0.001）. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.

Targeted metabolomic analysis of serum amino acids in heart failure patients

Heart failure (HF) has been recognized as a global epidemic with high rates of morbidity, hospitalization, and mortality. The role of amino acids, which provide the body with energy, in the development of HF is still unclear. The aim of this study was to explore changes in serum amino acids in patients with HF and identify potential biomarkers. First, the serum amino acid metabolism profiles of 44 patients with HF and 30 healthy controls (Con) were quantitatively measured. Then, candidate markers were identified through the utilization of T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis. The results found that there were 11 amino acid levels that were significantly different between patients with HF and Con. Based on ROC curve analysis, the biomarkers of eight amino acids (Glutamic acid, Taurine, l-aspartic acid, l-ornithine, Ethanolamine, l-Serine, l-Sarcosine, and Cysteine) showed high sensitivity and specificity (AUC > 0.90), and binary logistic regression analysis was used in MetaboAnalyst 5.0. Among the amino acids examined, six exhibited notable alterations in accordance with the severity of HF. In conclusion, this study cannot only provide clinicians with an objective diagnostic approach for the early identification of HF, but also enhances comprehension of the underlying mechanisms involved in the pathogenesis of HF.

Essential amino acids in total knee and hip joint replacement: a narrative review

The increasing availability of total joint replacement especially for knee and hip joints has increased their rates substantially across the globe. It is associated with increased risk of sarcopenia with loss of muscle mass and strength in the postoperative period. The supplementation of proteins along with exercises have been mainframe strategy to improve the functional ability after total knee arthroplasty and total hip arthroplasty. However, supplementation of proteins necessitates effective proteolytic digestion and conversion to amino acids for exerting substantial effects. In overcoming this challenge, supplementation with essential amino acids can be an attractive approach In this article, we review the clinical evidence with use of essential amino acids in patients undergoing TKA and THA. In the nine studies included in the review, seven assessed EAAs in TKA and two in THA. In TKA studies, improvement in muscle mass, muscle strength and functional recovery has been significant over 6 weeks postoperatively in majority of the studies. Over long term (2 years), improved recovery of rectus femoris and quadriceps had been reported. In THA as well, significant improvement in hip function and stability has been reported. Thus, EAAs in addition to the existing rehabilitation program are helpful to improve sarcopenia and enhances the recovery to perform activities of daily living. We propose from current evidence that administration of EAAs 7 to 10 days prior to planned TKA or THA and continued for 14 to 20 days in the postoperative period along with rehabilitation program is optimal in enhancing the muscle strength and help in physical functional recovery. Current evidence indicates supplementation with EAAs should be a part of routine management protocol in patients undergoing TKA or THA.

Deviations in the content of neurotransmitters amino acids in patients with chronic hepatopathies

Introduction. Some amino acids are neurotransmitters. These include glycine (Gly), gamma-aminobutyric acid (GABA), glutamate (Glu), and aspartate (Asp). The liver is an important organ for the metabolism of amino acids. Materials and methods. It was examined 24 patients with chronic hepatopathy: 12 patients with chronic HBV infection (group I) and 12 patients with hepatic steatosis (group II), the control group (CG) consisted of 12 practically healthy individuals. Quantitative determination of Asp, Glu, Gly and GABA in blood serum was carried out using liquid chromatography. Results. In most patients with chronic hepatopathy Gly and Asp levels were within the regional norms, GABA levels were higher, and Glu levels were below the reference values. In I-st group of patients the level of Gly was 18.76±1.45, GABA - 0.83±0.06, Asp - 5.56±0.97, and Glu - 6.34±0.70 mcM/ dL. In II-nd group: the level of Gly was 22.37±0.91, GABA 0.77±0.03, Asp - 5.16±0.74, and Glu - 7.87±1.47 mcM/dL. In CG: the level of Gly was 22.93±2.21, GABA - 0.55±0.06, Asp - 2.69±0.45, and Glu - 12.46±1.92 mcM/dL. Conclusion. A violation of neurotransmitter amino acids metabolism is found in chronic hepatopathy. A decrease in glycine and glutamate was observed in patients’ blood serum, with an increase in GABA and aspartate. These disorders are most profound in individuals with chronic viral infection B.

EE115 Cost-Effectiveness Analysis of Using Ketoanalogues of Essential Aminoacids in Patients With Chronic Kidney Disease in Kazakhstan

EE115 Cost-Effectiveness Analysis of Using Ketoanalogues of Essential Aminoacids in Patients With Chronic Kidney Disease in Kazakhstan

Amino Acid Profiling of Follicular Fluid in Assisted Reproduction Reveals Important Roles of Several Amino Acids in Patients with Insulin Resistance.

The global prevalence of insulin resistance (IR) is increasing continuously, influencing metabolic parameters and fertility. The metabolic changes due to IR can alter the molecular composition of plasma and other body fluids. Follicular fluid (FF) is derived mainly from plasma, and it is a critical microenvironment for the developing oocytes. It contains various metabolites and amino acids, and the quality of the oocytes is linked at least partially to amino acid metabolism. Our goal was to quantitatively determine the amino acid (AA) profile of FF in IVF patients and to compare IR and non-insulin resistance (NIR) groups to investigate the AA changes in their FF. Using UHPLC-based methods, we quantified the main 20 amino acids from human FF samples in the IR and NIR groups. Several amino acids (aspartate, glycine, glutamate, and cysteine) differed significantly (p < 0.05 or less) between the two groups. The most significant alterations between the IR and NIR groups were related to the glutathione metabolic pathway involving glycine, serine, and threonine. Since insulin resistance alters the amino acid composition of the FF, the oocytes may undergo metabolism-induced changes resulting in poor oocyte quality and less fertility in the insulin resistance groups.

Serum amino acid profiles in patients with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease characterized by weakness and rapid fatigue. Diagnostic methods used for myasthenia gravis are not conclusive and satisfactory, therefore it is necessary to develop reliable tools to help diagnose myasthenia gravis as early as possible. The aim of the study was to use HPLC–MS in conjunction with multivariate statistical analyses to investigate changes in the amino acid metabolic profiles between myasthenia gravis patients compared and controls. In addition, the effect of treatment regimens and myasthenia gravis type, on the observed changes in amino acid metabolic profiles were assessed. Serum levels of 29 amino acids were determined in 2 groups of individuals—28 patients with myasthenia gravis and 53 control subjects (CS). The results of our study indicate that serum levels of several amino acids in patients with myasthenia gravis changed significantly compared to the control group. Statistical analysis revealed differences between amino acids concentration in patients with different therapeutic scheme. In conclusion, amino acids may be involved in mechanisms underlying myasthenia gravis pathogenesis as well as may be potential biomarkers in MG patients diagnosis. However, considering the multifactorial, heterogenous and complex nature of this disease, validation on a larger study sample in further research is required before application into diagnostic practice.

Tissue and plasma free amino acid detection by LC-MS/MS method in high grade glioma patients.

The changes in serum amino acid profiles are evaluated in different types of cancers and screening tests were developed for estimating the risk of cancer by rapid analysis of plasma free amino acid (PFAA) levels. There is scarce evidence about the metabolomics analysis of PFAA in malignant gliomas. The aim of the present study was to identify the most promising diagnostic amino acid biomarkers that could be objectively measured for high-grade glioma and to compare their level with the tissue counterpart. In this prospective study, we collected serum samples from 22 patients with the pathological diagnosis of high-grade diffuse glioma according to WHO 2016 classification and 22 healthy subjects, and brain tissue from 22 controls. Plasma and tissue amino acid concentrations were analyzed applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Serum alanine, alpha-aminobutyric acid (AABA), lysine (Lys) and cysteine concentrations were significantly higher in high-grade glioma patients despite low levels of alanine and Lys in the tumor tissue. Aspartic acid, histidine and taurine were significantly decreased in both serum and tumors of glioma patients. A positive correlation was detected between tumor volumes and serum levels of latter three amino acids. This study demonstrated potential amino acids which may have diagnostic value for high-grade glioma patients by utilizing LC-MS/MS method. Our results are preliminary to compare serum and tissue levels of amino acids in patients with malignant gliomas. The data presented here may provide feature ideas about the metabolic pathways in the pathogenesis of gliomas.

Efficacy and tolerability of a specific blend of amino acids in patients with anorexia nervosa treated in a hospital setting: study protocol for a randomized controlled trial

BackgroundSpecific blends of essential amino acids (EAA) containing a high percentage of branched-chain amino acids preserves mitochondrial metabolism and higher physical resistance in elderly mice, increasing their survival and improving physical performance and cognitive functions in malnourished elderly patients. However, no study has been yet done on patients with anorexia nervosa (AN) who regain weight with specialized intensive treatment. The present study aims to evaluate the efficacy of supplementation with EAA on the change in lean body mass (LBM) and other physical and psychological outcomes in patients with AN who are undergoing specialist treatment for eating disorders.MethodsThis is a 13-week randomized, double-blind, placebo-controlled study. Patients will be randomized to either a mixture of a complex blend of EAA and intermediates of the tricarboxylic acid (TCA) cycle (citrate, malate, succinate) supplementation (or placebo) upon admission at the intensive residential and day-hospital treatment for eating disorders. Ninety-two participants with AN aged 16–50 years will be recruited from a specialized intensive treatment of eating disorders. Double-blind assessment will be conducted at baseline (T0) and the end of the 13 weeks of treatment (T1). The study’s primary aim is to evaluate the efficacy of supplementation with EAA and TCA intermediates on the change in lean body mass (LBM) with weight restoration in patients with AN who are undergoing specialist treatment for eating disorders. The secondary aims of the study are to assess the effect of dietary supplementation on physical fitness, weight restoration, modification of AN and general psychopathology, and psychosocial impairment.DiscussionThe study’s results will inform researchers and clinicians on whether supplementing a mixture of EAA and TCA cycle intermediates will improve the increase of LBM and other important physical and psychological outcomes in patients with AN who regain weight with specialized intensive treatment.Trial registrationNCT, NCT05290285. Registered on 22 March 2022.

Evaluation of characteristic metabolites of aromatic amino acids in patients with HIV infection at different stages of disease.

Acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, and antiretroviral therapy are usually associated with metabolic disorders. Screening for biomarkers to evaluate the progression of metabolic disorders is important for the diagnosis and treatment of HIV infection. This study aimed to establish and validate a method to quantify serum aromatic amino acid (AAA) metabolites as biomarkers of metabolic disorders in patients with HIV. The AAAs and metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Pearson's correlation, heatmap, and receiver operating characteristic curve analyses were used for statistical analysis. Under optimal detection conditions, the lower limits of phenylalanine (Phe), tryptophan (Trp), kynurenine (Kyn), tyrosine, phenylacetylglutamine (PAGln), and 5-hydroxytryptamine quantification reached 0.02, 0.02, 0.01, 0.02, 0.01, and 0.002 μg/ml, respectively, and the precision of intra- and inter-day was stay below 10.30%. Serum samples were stable for at least 6 months when stored at -80°C. The inter-group differences and associations between the biomarkers exhibited a particular volatility trend in PAGln, Trp, and Kyn metabolism in HIV-infected patients with metabolic syndrome. The developed method can be used for rapid and sensitive quantification of the AAA metabolism profile in vivo to further appraise the process of HIV infection, evaluate intervening measures, conduct mechanistic investigations, and further study the utility of PAGln, a characteristic metabolite of AAA, as a biomarker of HIV infection coupled with metabolic syndrome.

Abstract 15584: Metabolomic Signature of Fontan Circulation

Introduction: Patients born with a range of cardiac defects, not amenable to biventricular repair are palliated with establishment of Fontan circulation. Although majority of patients with Fontan circulation survive childhood, eventually they experience multi-system dysfunction, mainly frailty, impaired exercise capacity, blunted exercise-augmented hemodynamics, progressive liver fibrosis, and shortened survival. Fontan circulation associated biochemical abnormalities have not been well described. Materials and Methods: Twenty adult patients with Fontan circulation and 20 age- and sex-matched healthy subjects underwent a non-targeted metabolomics assessment using an LC-QTOF-MS system to detect potential Fontan-related biomarkers. These study participants were also investigated for markers of frailty, cardiopulmonary exercise testing, and resting as well as exercise-augmented hemodynamic evaluation. Results: A total of 1679 known plasma metabolites were detected in electrospray positive and negative modes among which 37 metabolites were significantly different (T-Test Unpaired (p&lt;0.05) followed by a multiple testing correction of p values (Benjamini-Hochberg)). These metabolites belonged to several classes of compounds including lipids, bile acids, amino acids, and derivatives. Several bile acids such as chenodeoxycholic acid glycine conjugate, glycoursodeoxycholic acid, and deoxycholic acid glycine conjugate were upregulated in patients with Fontan while 8-hydroxyguanine, N-arachidonoyl glycine, uracil, and cysteine were down-regulated in comparison to healthy subjects. Conclusion: In-depth plasma metabolomic analysis demonstrated metabolic pathways activation involved in bile acid formation, markers of oxidative stress, damage of DNA, whereas lower concentrations of several amino acids in patients with Fontan.

Capacitance-Based Biosensor for the Measurement of Total Loss of L-Amino Acids in Human Serum during Hemodialysis.

In this paper, we present a biosensor based on a gold nanoparticle (AuNP)-modified Pt electrode with an adjusted membrane containing cross-linked L-amino acid oxidase for the detection and quantification of total L-amino acids. The designed biosensor was tested and characterized using the capacitance-based principle, capacitance measurements after electrode polarization, disconnection from the circuit, and addition of the respective amount of the analyte. The method was implemented using the capacitive and catalytic properties of the Pt/AuNP electrode; nanostructures were able to store electric charge while at the same time catalyzing the oxidation of the redox reaction intermediate H2O2. In this way, the Pt/AuNP layer was charged after the addition of analytes, allowing for much more accurate measurements for samples with low amino acid concentrations. The combined biosensor electrode with the capacitance-based measurement method resulted in high sensitivity and a low limit of detection (LOD) for hydrogen peroxide (4.15 μC/μM and 0.86 μM, respectively) and high sensitivity, a low LOD, and a wide linear range for L-amino acids (0.73 μC/μM, 5.5 μM and 25-1500 μM, respectively). The designed biosensor was applied to measure the relative loss of amino acids in patients undergoing renal replacement therapy by analyzing amino acid levels in diluted serum samples before and after entering/leaving the hemodialysis apparatus. In general, the designed biosensor in conjunction with the proposed capacitance-based method was clinically tested and could also be applied for the detection of other analytes using analyte-specific oxidases.

Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury.

BackgroundAngiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is highly expressed in the kidneys. Beyond serving as a crucial endogenous regulator of the renin-angiotensin system, ACE2 also possess a unique function to facilitate amino acid absorption. Our observational study sought to explore the relationship between urine ACE2 (uACE2) and renal outcomes in COVID-19.MethodsIn a cohort of 104 patients with COVID-19 without acute kidney injury (AKI), 43 patients with COVID-19-mediated AKI, and 36 non-COVID-19 controls, we measured uACE2, urine tumor necrosis factor receptors I and II (uTNF-RI and uTNF-RII), neutrophil gelatinase-associated lipocalin (uNGAL). We also assessed ACE2 staining in autopsy kidney samples and generated a propensity-score matched subgroup of patients to perform a targeted urine metabolomic study to describe the characteristic signature of COVID-19.ResultsuACE2 is increased in patients with COVID-19, and further increased in those that developed AKI. After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with over 3-fold higher risk of developing AKI (OR 3.05, 95%CI:1.23‒7.58,p = 0.017). Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in patients with COVID-19, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2.ConclusionsElevated uACE2 is related to AKI in patients with COVID-19. The loss of tubular ACE2 during SARS-CoV-2 infection demonstrates a potential link between aminoaciduria and proximal tubular injury.

Levels of Acylcarnitines and Branched-Chain Amino Acids in Antipsychotic-Treated Patients with Paranoid Schizophrenia with Metabolic Syndrome.

Several studies have shown that patients with schizophrenia are at high risk for metabolic syndrome (MetS) and bioenergetic dysfunction. Because acylcarnitines are involved in bioenergetic pathways and reflect the functioning of mitochondria, we hypothesized that these compounds are biomarkers of MetS in schizophrenia. The aim of this work was to quantify acylcarnitines and branched-chain amino acids in patients with schizophrenia comorbid with MetS. The study included 112 patients with paranoid schizophrenia treated with antipsychotics. Among them, 39 subjects met criteria of MetS. Concentrations of 30 acylcarnitines and three amino acids in dry serum spots were measured by liquid chromatography coupled with tandem mass spectrometry. MetS patients were found to have higher levels of valeryl carnitine (C5), leucine/isoleucine, and alanine as compared with patients without MetS, indicating possible participation of these compounds in the pathogenesis of metabolic disorders in schizophrenia. In patients with paranoid schizophrenia with or without MetS, lower levels of carnitines C10, C10:1, C12, and C18 were recorded as compared with the healthy individuals (n = 70), implying deterioration of energy metabolism. We believe that this finding can be explained by effects of antipsychotic medication on an enzyme called carnitine-palmitoyl transferase I.

Estimating the level of amino acids in patients with liver disease by amino acid analyzer

Background: Amino acid identification can be a reliable approach to noninvasive diagnosis of liver disease. This is because liver disease can be a cause of impaired amino acid metabolism. Therefore, a method for determining amino acids in blood that is applicable for clinical purposes is essential. Objectives: The aim of this study was to find differences in amino acid levels between patients with liver disease and a control group. Material and Methods: Samples of peripheral venous blood were obtained from a group of patients with liver disease (n = 40 women at an average age of 37-70 years and 40men at an average age of 35-70 years) and control group (n = 40 women at an average age of 35- 70 years and 40 men at an average age of 35 - 70 years). Before separation, The amino acids were derived using orthophalenealdehyde (OPA).For separation, a reverse phase shaft was used. The flow was monitored with a fluorescence detector. Results. There were statistically significant differences in the concentrations of some amino acids between patients and the control group, as well as between women and men. Relationships between some amino acids, markers of liver blood tests, and lipid metabolism were observed.

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p&lt;0,05) and Tyr (r=-0,583, p&lt;0,05), as well as the level of Phe with total cholesterol (r=-0,461, p&lt;0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p&lt;0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p&lt;0,05), and the level of Tyr with LDL (r=0,349, p&lt;0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target.

Implications for the metabolic fate of oral glutamine supplementation within plasma and erythrocytes of patients with sickle cell disease: A pharmacokinetics study

ObjectivesL-Glutamine is FDA-approved for sickle cell disease (SCD), yet the mechanism(s)-of-action are poorly understood. We performed a pharmacokinetics (pK) study to determine the metabolic fate of glutamine supplementation on plasma and erythrocyte amino acids in patients with SCD. DesignA pK study was performed where patients with SCD fasting for > 8 h received oral L-glutamine (10 g). Blood was analyzed at baseline, 30/60/90 min/2/3/4/8 hrs. A standardized diet was administered to all participants at 3 established time-points (after 2/5/7hrs). A subset of patients also had pK studies performed without glutamine supplementation to follow normal diurnal fluctuations in amino acids. SettingComprehensive SCD Center in Oakland, California ResultsFive patients with SCD were included, three of whom performed pK studies both with and without glutamine supplementation. Average age was 50.6 ± 5.6 years, 60% were female, 40% SS, 60% SC. Plasma glutamine levels increased significantly after oral glutamine supplementation, compared to minimal fluctuations with diet. Plasma glutamine concentration peaked within 30-min of ingestion (p = 0.01) before decreasing to a plateau by 2-h that remained higher than baseline by 8 h. Oral glutamine also increased plasma arginine concentration, which peaked by 4-h (p = 0.03) and remained elevated through 8-h. Erythrocyte glutamine levels began to increase by 8-h, while erythrocyte arginine concentration peaked at 4-h. ConclusionsOral glutamine supplementation acutely improved glutamine and arginine bioavailability in both plasma and erythrocytes. This is the first study to demonstrate that glutamine therapy increases arginine bioavailability and may provide insight into shared mechanisms-of-action between these conditionally-essential amino acids.

Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase.

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography–mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients’ fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.

Monitoring of circulating amino acids in patients with pancreatic cancer and cancer cachexia using capillary electrophoresis and contactless conductivity detection.

Branched chain amino acids (BCAAs), alanine and glutamine are determined in human plasma by capillary electrophoresis with contactless conductivity detection (CE/C4 D). The baseline separation of five amino acids from other plasma components is achieved on the short capillary effective length of 18cm in 3.2mol/L acetic acid with addition of 13% v/v methanol as background electrolyte. Migration times range from 2.01min for valine to 2.84min for glutamine, and LODs for untreated plasma are in the interval 0.7-0.9μmol/L. Sample treatment is based on the addition of acetonitrile to only 15μL of plasma and supernatant is directly subjected to CE/C4 D. Circulating amino acids are measured in patients with pancreatic cancer and cancer cachexia during oral glucose tolerance test. It is shown that patients with pancreatic cancer and cancer cachexia syndrome exhibit low basal circulating BCAAs and glutamine levels and loss of their insulin-dependent suppression.