scholarly journals Dynamic derangement in amino acid profile during and after a stroke-like episode in adult-onset mitochondrial disease: a case report

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Mai Fukuda ◽  
Yoshiro Nagao

Abstract Background Maternally inherited diabetes and deafness, and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are examples of mitochondrial diseases that are relatively common in the adult population. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are assumed to be associated with decreases in arginine and citrulline. Biomarkers, such as growth differentiation factor-15, were developed to assist in the diagnosis of mitochondrial diseases. Case presentation A 55-year-old Japanese man, an insulin user, presented after a loss of consciousness. A laboratory test showed diabetic ketoacidosis. He and his mother had severe hearing difficulty. Bilateral lesions on magnetic resonance imaging, the presence of seizure, and an elevated ratio of lactate to pyruvate, altogether suggested a diagnosis of mitochondrial disease. Mitochondrial DNA in our patient’s peripheral blood was positive with a 3243A>G mutation, which is the most frequent cause of maternally inherited diabetes and deafness, and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. As a result, maternally inherited diabetes and deafness/mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes was diagnosed. We measured growth differentiation factor-15 and multiple amino acids in his blood, longitudinally during and after the stroke-like episode. Growth differentiation factor-15 was increased to an immeasurably high level on the day of the stroke-like episode. Although his diabetes improved with an increased dose of insulin, the growth differentiation factor-15 level gradually increased, suggesting that his mitochondrial insufficiency did not improve. Multiple amino acid species, including arginine, citrulline, and taurine, showed a decreased level on the day of the episode and a sharp increase the next day. In contrast, the level of aspartic acid increased to an extremely high level on the day of the episode, and decreased gradually thereafter. Conclusions Growth differentiation factor-15 can be used not only for the diagnosis of mitochondrial disease, but as an indicator of its acute exacerbation. A stroke-like episode of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes reflects a drastic derangement of multiple amino acids. The involvement of aspartic acid in the episodes should be explored in future studies.

Author(s):  
V. Kondratiuk ◽  

The article considers the efficiency of using complete compound feeds with different levels of lysine and methionine in rearing larvae and juveniles of rainbow trout. The purpose of the experiment was to establish the effect of different amino acid levels in nutrition of juvenile trout on its productivity. For this purpose, five experimental groups were formed by the method of analogues. The experiment lasted 35 days and was divided into two periods: equalizing (5 days) and main (30 days). During the equalizing period, the experimental fish consumed feed of the control group. In the main period, the levels of lysine and methionine in experimental feeds for different experimental groups of trout ranged from 2.9 to 3.3% and from 0.95 to 3.15%, respectively. It is proved that increasing the content of lysine and methionine in feed for larvae and juveniles of rainbow trout to the levels of 3.2 and 1.1%, respectively, promotes increase in their weight by 10.7% (p <0.01) and growth intensity - by 6.4-11.1%, while further increase in these amino acids content in the feed reduces the productivity of fish. Polynomial equations for determining the juvenile fish weight at any stage of rearing at a high level of determination for each of the experimental groups have been calculated. It was found that with an increase in the content of lysine and methionine in feed to the levels of 3.2 and 1.1%, respectively, reduces feed costs per 1 kg of weight gain in trout larvae and juveniles by 4.1%, and a further increase in levels of these amino acids to 3.3 and 1.15%, respectively, increase this index by 1.1%. The experimental fish survival ranged from 83.9 to 85.1%. In the production of trout according to the criteria of maximum productivity and to the economic optimization criteria, it is recommended to use complete feed with the level of lysine - 3.2% and methionine - 1.1% for feeding trout larvae and juveniles.


2021 ◽  
pp. 219-225
Author(s):  
Галина Табаленкова

The results of studies of the qualitative composition and quantitative content of amino acids (AAs) in the leaves of three plant species of the genus Artemisia, widespread in the Elton region, were presented. Protein AAs were determined on an AAA T-339 amino acid analyzer (Czech Republic) after hydrolysis of a sample in 6N HCl at 105 °C for 24 h, free AAs – on an AAA-400 amino acid analyzer (Czech Republic) in a lithium buffer system. The protein AAs amount varied from 66 mg / g in A. lerchiana to 113 mg / g dry weight in A. santonica. 17 AAs were found in composition of these species, aspartic and glutamic acids were dominant. The content of free AAs varied from 4.4 mg / g in A. santonica to 8.3 mg / g dry weight in A. pauciflora. 14 AAs have been identified, among them proline was the predominant free AA. The share of proline was 75-81% of the total free AAs. Among the minor components, 3-4 compounds with a content above 2% dominated. The free AAs contain 3 non-proteinogenic ones (ornithine, citruline, and γ-aminobutyric acid). A. lerchiana and A. pauciflora species were similar in protein and free amino acids, probably due to the same growing conditions. A high level of free proline, together with a complex of biologically active substances in Artemisia species, which grow abundantly in the Elton region, allow to consider the possibility of their use as a medicinal raw material.


2018 ◽  
pp. 75-82 ◽  
Author(s):  
Мухендис (Mukhendis) Мамедгусейин оглы (Mamedgusejin ogly) Джахангиров (Cahangirov) ◽  
Микаил (Mikail) Акпер оглы (Аkper ogly) Магеррамов (Маharrаmov)

It was shown that the scent and taste of tea are determined by the level of protein and amino acid. Certainly, protoingens that make up most part of proteins are noted among amino acids. All of them are considered L-shaped. Green tea mostly consists of proteins. Even the high level protein doesn’t adversely impact the quality of tea yet that of black tea might be negatively influenced by that. Also, its taste will also be worsened by that.As a result of analysis 16 amino acids and 8 unsubstituted substance was found. The main part of amino acid is taken by teanin. It take 41.3% of Azerbaijan-1, 38.8% of Kolxida types respectively. In all stages of tea leaf processing the decrease of teanin and increase of glutamin is witnessed. Also, the loss of teanin happens during the purification (by 34%) and the fading stages.As a result of the work carried out, it has been found that the size of the tea leaf particle, the temperature and the extraction time influence the extraction of the theanine. The optimum are: the size of the tea leaf particle is 200–450 mkm, the extraction temperature is 80–85 °C, and the extraction time is 20–25 minutes.


Thorax ◽  
2019 ◽  
Vol 74 (11) ◽  
pp. 1099-1101 ◽  
Author(s):  
Brian J Rosenberg ◽  
Michio Hirano ◽  
Catarina M Quinzii ◽  
Elizabeth Colantuoni ◽  
Dale M Needham ◽  
...  

Muscle mitochondrial dysfunction is implicated in intensive care unit-acquired weakness, but there is no serum biomarker of muscle mitochondrial function for critical illness survivors. Higher serum growth differentiation factor-15 (GDF-15) is a biomarker of inherited mitochondrial myopathy disease and is associated with mortality in several age-related diseases. Among 142 older (age ≥ 65 years) survivors of acute respiratory failure, we found that higher serum GDF-15 measured during the week prior to hospital discharge was cross-sectionally associated with weaker diaphragm, limb and hand-grip strength, and longitudinally associated with lower rates of functional recovery over 6 months, independent of age, sex, pre-existing disability, comorbidity, frailty, Acute Physiology and Chronic Health Evaluation II scores and concurrent interleukin-6 levels.


2000 ◽  
Vol 44 (11) ◽  
pp. 2985-2990 ◽  
Author(s):  
Hiroshi Kakeya ◽  
Yoshitsugu Miyazaki ◽  
Haruko Miyazaki ◽  
Katherine Nyswaner ◽  
Brian Grimberg ◽  
...  

ABSTRACT High-level azole resistance in the Darlington strain ofCandida albicans was investigated by gene replacement inC. albicans and expression in Saccharomyces cerevisiae. We sequenced the ERG11 gene, which encodes the sterol C14α-demethylase, from our copy of the Darlington strain. Both alleles contained the histidine for tyrosine substitution at position 132 (Y132H) reported in Darlington by others, but we also found a threonine-for-isoleucine substitution (I471T) not previously reported in the C. albicans ERG11. The encoded I471T change in amino acids conferred azole resistance when overexpressed alone and increased azole resistance when added to the Y132H amino acid sequence in an S. cerevisiae expression system. Replacement of one copy of ERG11 in an azole-susceptible strain of C. albicans with a single copy of the Darlington ERG11 resulted in expression of the integrated copy and a modest increase in azole resistance. The profound azole resistance of the Darlington strain is the result of multiple mutations.


2016 ◽  
Vol 54 (10) ◽  
pp. 8110-8116 ◽  
Author(s):  
Xinbo Ji ◽  
Lizhen Zhao ◽  
Kunqian Ji ◽  
Yuying Zhao ◽  
Wei Li ◽  
...  

Parasitology ◽  
1972 ◽  
Vol 64 (3) ◽  
pp. 379-387 ◽  
Author(s):  
L. H. Chappell ◽  
G. C. Southworth ◽  
C. P. Read

During 2 min incubations of Trypanosoma gambiense (bloodstream form) with [U-14C]glucose (1 mM) over 60% of absorbed label was detected in free alanine. In the presence of 12·5 mM unlabelled alanine, the amount of alanine synthesized from glucose was reduced by less than 10%. These data support previous observations on the high level of transaminase activity in African human trypanosomes.Alanine, aspartate and glutamate were metabolized to various other free amino acids whereas a significant amount of label derived from [14C]arginine could not be accounted for by amino acid assay.The sulphur containing amino acids, cysteic acid and taurine, were apparently synthesized from alanine, glutamate and arginine. The significance of these syntheses is poorly understood.Following incubations of trypanosomes for 2 min in exogenous amino acids the internal free pool became imbalanced due to accumulation and metabolism of the substrate amino acid.Evidence obtained indicated that the level of free endogenous glutamate may be rate limiting for the glutamate-pyruvate transaminase system.


1972 ◽  
Vol 52 (2) ◽  
pp. 377-384 ◽  
Author(s):  
L. J. FISHER

High, low, and zero quantities of methionine, histidine, or lysine were infused intravenously into lactating cows fed a corn–corn silage–urea ration to assess whether any of these amino acids were limiting for milk production. Feed intake was significantly higher (P < 0.05) with the low level of methionine infusion than with either the high level or saline infusions. Milk yield was not affected (P > 0.05) by any treatments, but protein yield was significantly greater (P < 0.05) with the low than with the high or zero levels of infusion of methionine, and the infusion of either level of histidine significantly decreased (P < 0.05) milk protein yield compared with zero level of infusion. The changes in levels of plasma amino acids that occurred during these studies have been interpreted as implying that methionine was the first limiting and either valine, leucine, or isoleucine was the second limiting amino acid for milk production.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.V Belokurova ◽  
T.P Gizatulina ◽  
N.Y.U Khorkova ◽  
L.U Martyanova ◽  
T.I Petelina ◽  
...  

Abstract Background The presence of left atrial/left atrial appendage (LA/LAA) thrombus is used as a surrogate marker of potential stroke in patients (pts) with atrial fibrillation (AF). Purpose To assess the role of growth differentiation factor 15 (GDF-15) level, clinical and echocardiographic (EchoCG) data as predictors of LA/LAA thrombus in pts with nonvalvular AF. Methods Out of 158 pts with nonvalvular AF admitted to Cardiology Center for radiofrequency ablation or elective cardioversion in 2019–2020 2 groups were formed according to transesophageal EchoCG results: group 1 included pts without LA/LAA thrombus (n=102, mean age 59.5±6.0 years) and group 2 (n=42, mean age 60.9±8.8 years) – pts with LA/LAA thrombus. Arterial hypertension was found in 93 pts of group 1 (91%) and in 40 pts of group 2 (95%, p=0.42), coronary artery disease - in 53 pts (52%) and 29 pts (69%), respectively (p=0.06). Both groups did not differ in frequency and spectrum of oral anticoagulants administration. General clinical assessment, EchoCG, and laboratory tests were performed, including GDF-15 (pg/ml) levels using Human GDF-15/MIC-1 ELISA kit and NT-proBNP (pg/ml) in blood. Results Pts with LA/LAA thrombus more often had persistent AF, while paroxysmal AF was more common in pts without thrombus. There was a tendency to more significant congestive heart failure in group 2. Mean CHA2DS2-VASc score was higher in pts with LA/LAA thrombus, also there was a tendency to a larger proportion of pts with scores ≥3. According to EchoCG data, sizes and volumes of both atria, right ventricle, end-systolic volume, left ventricular (LV) size, pulmonary artery systolic pressure and LV mass index were higher in group 2; LV ejection fraction (LVEF) was normal in both groups, but it was significantly lower in pts with LA/LAA thrombus: 59.1±5.1 and 64.0±7.3, respectively (p&lt;0.001). GDF-15 and NT-proBNP levels were significantly higher in group 2 compared to group 1: p=0.00025 and p=0.ehab724.048801 respectively. According to ROC analysis cut-off were set at level &gt;935.0 pg/ml for GDF-15 (AUC=0.705, 95% CI 0.609–0.800, p&lt;0.001) and &gt;143 pg/ml for NT-proBNP (AUC=0.759, 95% CI 0.670–0.849, p&lt;0.001). Multivariate logistic regression revealed the following variables as independent predictors of LAAT: GDF-15 &gt;935.0 pg/ml (OR=4.132, 95% CI 1.305–13.084) and LVEF (OR=0.859, 95% CI 0.776–0.951). According to ROC analysis, the model had a good quality: AUC=0.776 (p&lt;0.001), sensitivity was 78.3%., specificity - 78.3%. Conclusion High level of GDF-15 (&gt;935.0 pg/ml) along with lower LVEF are independent predictors of LA/LAA thrombus in pts with nonvalvular AF. FUNDunding Acknowledgement Type of funding sources: None.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 553-553 ◽  
Author(s):  
Toshihiko Tanno ◽  
Natarajan V. Bhanu ◽  
Patricia A. Oneal ◽  
Sung-Ho Goh ◽  
Pamela Staker ◽  
...  

Abstract Iron overload causes considerable morbidity associated with thalassemia due to inappropriate suppression of the iron regulator, hepcidin. One possible explanation for this phenomenon is that protein(s) that are normally secreted into the marrow microenvironment by erythroblasts become endocrine signals in patients with thalassemia due to the myeloproliferative nature of the disease. To test this hypothesis, progenitor and precursor cell transcriptional profiles were generated with Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays using primary erythroblasts cultured from 15 healthy human donors. For this study, informatic analyses were focused upon 54 members of the TGF–B/BMP superfamily. Among the subset of genes identified by this screen, evidence for high-level expression of a gene named growth differentiation factor 15 (GDF15) was discovered in the precursor cell profiles. Quantitative PCR, Western, and ELISA analyses confirmed expression and secretion of GDF15 during erythroblast maturation. GDF15 is an apoptosis-associated protein expressed primarily by the placenta. To determine whether GDF15 serves as a regulator of hepcidin expression, hepcidin expression assays were performed using a human hepatoma cell line (HuH-7). BMP2 and BMP4 were studied for comparison. Addition of BMP2 and BMP4 (range 10,000–500,000 pg/ml) resulted in dosed increases in hepcidin mRNA (5–30 fold). At the concentrations of GDF15 normally found in human blood (500 pg/ml), a 2-fold increase in the expression of hepcidin was measured compared to matched cultures containing no supplemental GDF15. However, GDF15 dosed to levels above 5,000 pg/ml resulted in a significant reduction in hepcidin expression. Next, plasma levels of GDF15 were measured in the peripheral blood of 162 donors (donor groups included healthy controls, sickle-cell syndromes, thalassemia syndromes, and other causes of anemia) to determine whether plasma GDF15 levels are dysregulated in thalassemia. Plasma samples from 21 hereditary hemochromatosis donors provided evidence that significantly elevated GDF15 expression is not associated with iron overload in the absence of erythroid pathology. Compared with mean plasma GDF15 levels of 536±222 pg/ml among the control samples, only patients with thalassemia intermedia, thalassemia major, and HbE-beta thalassemia showed significantly elevated plasma levels of GDF15 (9 donors; mean GDF15 24,600 pg/ml; range 8,980–75,100 pg/ml; p<0.01). Elevated ferritin levels (>370 ug/L) were noted in each of those patients regardless of their transfusion or chelation history. These novel findings suggest that GDF15 is secreted from human erythroblasts, released into the circulation at extremely high levels in thalassemia patients, and contributes to iron overloading in those patients by suppressing hepcidin expression.


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