Reduction In Amino Acid Concentrations Research Articles

Safety assessment of sapropterin dihydrochloride: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS).

Sapropterin dihydrochloride is the first drug for the therapy of phenylketonuria, which is a rare disease that occurs one of 10,000-15,000 newborns. As a result, detailed and comprehensive reports on the safety of sapropterin in large, real-world populations are required. The purpose of this study is to undertake a complete analysis of sapropterin's adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database. We retrieved reports of adverse events with sapropterin as the principal suspect from FAERS between the first quarter of 2008 and the first quarter of 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals. The study collected 4,953 suspected AE cases from the FAERS database, with sapropterin as the major suspect. A total of 130 positive signals were obtained utilizing the ROR, PRP, and BCPNN. The FAERS database revealed that common clinical AEs of sapropterin included vomiting, upper respiratory infection, rhinorrhea, and a reduction in amino acid concentrations. Furthermore, we detected probable unexpected adverse events (AEs) using disproportionality analysis, including gastroesophageal reflux disease, flatulence, influenza, ear infection, viral infection, pharyngitis streptococcal, spontaneous abortion, and nephrolithiasis. By analyzing huge amounts of real-world data from the FAERS database, we found potential novel AEs of sapropterin using disproportionate analysis. It is advantageous for healthcare professionals and pharmacists to focus on efficiently managing sapropterin's high-risk adverse events, improving drug levels in clinical settings, and ensuring patient medication safety.

Effect of high-temperature, short-time cooking conditions on in vitro protein digestibility, enzyme inhibitor activity and amino acid profile of selected legume grains

African yam beans (Sphenostylis stenocarpa), Bambara groundnut (Vigna subterranean) and Pigeon pea (Cajanus cajan) flours were extruded in a single screw extruder at two extrusion temperatures; 100 °C and 140 °C, and the effect of extrusion cooking temperature on the chemical composition; crude protein, crude fibre, ether extract and nitrogen-free extracts, protein digestibility, enzyme inhibitor activity and amino acid profiles was investigated. The crude protein, amino acid profile and ether extract of the grain legumes were negatively affected (p < 0.05) by the extrusion cooking process, with a significant increase in nitrogen-free extracts for all grain legumes, and increased crude fibre of Bambara groundnut and Pigeon pea extrudates. Extrusion cooking of African yam beans and Pigeon pea produced extrudates with significantly lower trypsin, chymotrypsin and amylase inhibitor activity as well as improved protein digestibility. However, extrusion cooking did not modify the chymotrypsin and amylase inhibitor activity of Bambara groundnut extrudates. Extrusion cooking at 140 °C compared to 100 °C significantly reduced the protein quality of extrudates resulting in 22.94–51.27%, 5.11–25.18%, and 7.78–38.42% reduction in amino acid concentration of African yam beans, Bambara groundnut and Pigeon pea, respectively.

Lanthanum Affects Bell Pepper Seedling Quality Depending on the Genotype and Time of Exposure by Differentially Modifying Plant Height, Stem Diameter and Concentrations of Chlorophylls, Sugars, Amino Acids, and Proteins.

Lanthanum (La) is considered a beneficial element, capable of inducing hormesis. Hormesis is a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition. Herein we tested the effect of 0 and 10 μM La on growth and biomolecule concentrations of seedlings of four sweet bell pepper (Capsicum annuum L.) varieties, namely Sven, Sympathy, Yolo Wonder, and Zidenka. Seedling evaluations were performed 15 and 30 days after treatment applications (dat) under hydroponic greenhouse conditions. Seedling height was significantly increased by La, growing 20% taller in Yolo Wonder plants, in comparison to the control. Similarly, La significantly enhanced shoot diameter, with increases of 9 and 9.8% in measurements performed 15 and 30 dat, respectively, as compared to the control. Likewise, La-treated seedlings had a higher number of flower buds than the control. An increase in the number of leaves because of La application was observed in Yolo Wonder seedlings, both 15 and 30 dat, while leaf area was augmented in this variety only 30 dat. Nevertheless, La did not affect dry biomass accumulation. La effects on biomolecule concentration were differential over time. In all varieties, La stimulated the biosynthesis of chlorophyll a, b and total 15 dat, though 30 dat only the varieties Sympathy and Yolo Wonder showed enhanced concentrations of these molecules because of La. Total soluble sugars increased in La-treated seedlings 30 dat. Interestingly, while most varieties exposed to La showed a reduction in amino acid concentration 15 dat, the opposite trend was observed 30 dat. Importantly, in all varieties evaluated, La stimulated soluble protein concentration 30 dat. It is important to note that while chlorophyll concentrations increased in all varieties exposed to La, both 15 and 30 dat, those of soluble sugars and proteins consistently increased only 30 dat, but not 15 dat. Our results confirm that La may improve seedling quality by enhancing some growth parameters and biomolecule concentrations, depending on the genotype, and time of exposure.

Substrate utilization during incubation in meat juice medium of psychrotolerant clostridia associated with blown pack spoilage

Several new species of psychrophilic or psychrotolerant clostridia have been identified in recent years. Some of these may be involved in ‘blown pack’ spoilage (BPS) of vacuum packaged beef. Organisms that cause BPS must produce large volumes of gas while utilizing substrates available in raw meat. Therefore, Clostridium algoriphilum, Clostridium algidixylanolyticum, Clostridium bowmanii, Clostridium frigoris, Clostridium frigidicarnis, Clostridium gasigenes, Clostridium lacusfryxellense, Clostridium psychrophilum, Clostridium tagluense and Clostridium vincentii were grown in meat juice medium (MJM), and changes in substrate concentrations were monitored to assess the potential for gas production by each organism. All 10 species were able to grow exponentially on glucose with simultaneous hydrolysis of glycogen, reaching maximum values for absorbance at 600 nm of 0.3–1.90. All ceased growing when glucose and glycogen were still detectable in the growth medium. C. frigidicarnis utilized most of the amino acids available in MJM and reduced the concentration of total amino acids by 10 mM. The other 9 species caused little or no reduction in amino acid concentrations. C. algidixylanolyticum and C. frigidicarnis utilized glucose, glycogen and lactate simultaneously during growth and after growth ceased. C. algoriphilum and C. frigoris commenced utilization of lactate, while continuing utilization of glucose and glycogen, only after growth ceased, but utilization of lactate by C. algoriphilum was weak. C. psychrophilum ceased utilization of glucose and glycogen but initiated weak utilization of lactate after growth ceased. The other 5 species did not utilize any substrate after growth ceased. The utilization of glucose, glycogen and relatively large amounts of lactate by C. algidixylanolyticum, C. frigoris, and C. frigidicarnis after growth ceased indicates that these organisms have the potential to cause BPS. The other 7 species appear to lack such potential.

Metabonomic investigations of age- and batch-related variations in female NMRI mice using proton nuclear magnetic resonance spectroscopy

The NMRI outbred mouse model is widely used for studying metabolic disease, toxicity, and infection, yet information regarding baseline metabolism of this murine strain is relatively sparse. Using different batches of female NMRI mice, we assessed the stability of the metabolic phenotype with increasing age and weight, and determined the influence of acclimatization on the metabolic profile of biofluids (urine, plasma, and faecal water). Differences in urinary concentrations of 3-ureidopropionate, 2-oxoisocaproate, trimethylamine, and glycine were detected between three batches of 9-week-old female NMRI mice using proton nuclear magnetic resonance ((1)H NMR) spectroscopy coupled with multivariate statistical analysis. An acclimatization period of 2 weeks was imposed after the mice entered the laboratory environment. Strong differences in the faecal metabolome pre- and post-acclimatization were found (reduction in amino acid concentrations), whilst the urine metabolome showed increased levels of trimethylamine-N-oxide, phenylacetyl glycine, and hippurate with decreased excretion of formate and betaine post-acclimatization. Temporal variation in the metabolite profiles over a 16-week study stabilized around 7-week-old animals. The results from this study strongly argue for inclusion of an acclimatization period prior to starting an investigative procedure, and suggest that the metabolic phenotypes of female NMRI mice are more stable at around 7 weeks of age. We have also identified a set of metabolites that are more susceptible to variation in concentration. This information can serve as a benchmark in order to establish confidence in systematic variation attributable to pathology or therapeutic intervention above the background metabolic variation in the NMRI mouse.

Amino acid racemization in lacustrine ostracodes, part I: effect of oxidizing pre-treatments on amino acid composition

Bleaching biominerals reduces the concentration of amino acids to a residual fraction which is thought to be preserved within intra-crystalline proteins. Intra-crystalline amino acids represent a relatively closed-system and may be superior for amino acid geochronological and paleothermometry investigations. Here we quantify the effects of extended bleaching (to 144 h) on amino acid concentrations and d/ l values in the valves of seven modern ostracode species. Then we compare the effects of increasingly aggressive pre-treatments (sonication, exposure to 3% hydrogen peroxide for 2 h, and exposure to 10% bleach for 48 h) on amino acid concentrations and d/ l values in fossil ostracode ( Candona) valves from numerous locations throughout the western United States and northern Mexico. Bleaching modern ostracode valves results in a rapid order-of-magnitude reduction in amino acid concentrations and a slight increase in d/ l values. Amino acid concentrations in five of the seven modern species increased slightly after prolonged exposure to bleach, suggesting that bleaching weakens a resistant protein source within the ostracode valves. Increasingly aggressive pre-treatments had virtually no effect on amino acid concentrations, d/ l values, or inter-sample variability in fossil Candona valves older than about 1 ka. Candona valves younger than about 1 ka showed a progressive decrease in amino acid concentrations with more aggressive oxidizing pre-treatments. Valves older than 1 ka generally had amino acid concentrations < 10 nM mg −1. A delayed increase in amino acid concentrations (15–30 nM mg −1), followed by a gradual decrease to residual concentrations consistently < 10 nM mg −1, was observed in both outcrop and core samples. We propose that a large amount of weakly bound proteins is leached geologically instantaneously from Candona valves. Long-term (10’s of ka) diagenesis gradually weakens and then destroys a secondary pool of tightly bound proteins contained within the valves. Residual amino acid concentrations are likely derived from intra-crystalline proteins and resistant inter-crystalline proteins that are essentially immune to leaching. Candona valves deposited in pluvial Lake Chewaucan and exposed in sediments that crop out along the Ana River, Oregon, have unexpectedly well-preserved proteins and lower d/ l values compared to fossil Candona valves of similar age from other locations. The Ana River results argue for developing site-specific calibrations for amino acid geochronology or paleothermometry studies that utilize ostracodes.

Effect of Atropine on Milk Protein Yield by Dairy Cows with Different β-Lactoglobulin Phenotypes

The objective of this study was to determine the response of individual milk proteins to a reduction in amino acid (AA) availability induced by atropine and to determine whether the response was different in cows with different β-lactoglobulin (LG) phenotypes. Six cows that were homozygous for the A variant of β-LG and six cows that were homozygous for the B variant of β-LG were each given a single subcutaneous injection of saline or 20mg of atropine. In both groups of cows, atropine decreased milk yield by 30% and reduced the concentration of α-lactalbumin (LA) by 25 to 30% at 8h following injection. Eight hours after atropine injection, yield of β-LG was 41% lower than it was following saline injection, and yield of β-casein (CN) after atropine injection declined 16% relative to saline. Concentrations of BSA and the ratio of γ-CN to β-CN, which reflects plasmin activity in milk, were significantly increased after administration of atropine. Although the response to atropine tended to be more pronounced in cows that were homozygous for β-LG B, they were not significantly different from the response of cows that were homozygous for β-LG A. The differential response of individual proteins to a reduction in AA concentrations in whole blood suggested that susceptibility to restriction in substrate availability differed for individual proteins. The concentration of lactose in plasma did not change, which implied that the integrity of the mammary epithelial barrier was not compromised when AA derived from blood were diminished. The consistent concentration of lactose combined with the minimal increase in total yield of BSA in milk following atropine treatment indicated that the increased concentration in milk of proteins derived from serum was due to the concentrating effect of lower milk volume.

Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 gene transcription by hormones and provision of amino acids in rat hepatocytes.

Synthesis of insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) is altered in diabetes and malnutrition, but underlying processes are poorly understood. To study molecular mechanisms, we examined regulation of IGF-I and IGFBP-1 gene transcription in primary cultures of rat hepatocytes. Transcription of the IGF-I and IGFBP-1 genes was measured as incorporation of [alpha-32P]UTP into preinitiated message in isolated nuclei. IGFBP-1 gene transcription was not sensitive to reduction in amino acid concentration from 5x to 0.5x rat arterial plasma levels. However, IGF-I gene transcription fell 60-70% in response to reduced provision of amino acids. Culture with 10(-9) M insulin lowered IGFBP-1 gene transcription 50% below control levels (10-11 M) but did not affect IGF-I gene transcription; 10(-6) M insulin raised IGF-I gene transcription 2-fold. After an acute reduction in insulin concentration, IGFBP-1 transcription began to rise within 30 min, but IGF-I gene transcription was unchanged over 120 min. Similarly, 3-6 h were required for stimulation of IGF-I gene transcription by insulin, but a 40% decrease in IGFBP-1 gene transcription could be detected within 15 min after adding 10(-6) M insulin, and suppression of IGFBP-1 transcription by insulin was unaffected by the presence of cycloheximide. Effects of insulin on IGFBP-1 gene transcription were not mimicked or antagonized by phorbol ester.(ABSTRACT TRUNCATED AT 250 WORDS)

An excitant amino acid projection from the medial prefrontal cortex to the anterior part of nucleus accumbens in the rat.

High-affinity uptake of neurotransmitter substrates in synaptosome-containing homogenates and tissue concentrations of amino acids were examined in subcortical areas 5-6 days after bilateral N-methyl-D-aspartate lesions confined to rat medial prefrontal cortex. D-[3H]Aspartate (32% of control) and [3H] gamma-aminobutyric acid ( [3H]GABA) (60% of control) uptakes were significantly reduced in medial prefrontal cortex, whereas [3H]choline (110% of control) uptake was unchanged, suggesting the production of axon-sparing lesions. The uptake of D-[3H]aspartate (76% of control), but not of [3H]GABA or [3H]choline, was significantly reduced in nucleus accumbens, with no concomitant reduction in amino acid concentrations. When examined in serial coronal sections, reduced D-[3H]aspartate uptake was confined to the most anterior 500 micron of nucleus accumbens (67% of contralateral sample). No significant reductions of uptake or amino acid concentrations were observed in caudate putamen or ventral tegmental area. These results suggest a role for glutamate or aspartate as neurotransmitters in projections from medial prefrontal cortex to anterior nucleus accumbens. Medial prefrontal cortex may represent the major excitatory cortical input to the nucleus accumbens.

Changes in individual plasma amino acids following experimentally induced sand fly fever virus infection

Fasting concentrations of 21 individual plasma amino acids were determined in daily (7:30 a.m.) serial samples from eight volunteers infected with sand fly fever virus and compared to values obtained in six separate daily preexposure baseline measurements in each volunteer, as well as to serial measurements in three unexposed control subjects. By 47 hr after inoculation and before the onset of fever or other clinical indications of infection, most individual plasma amino acids were significantly depressed below preexposure values. These changes began before the marked decrement in protein intake during the illness. Such changes in plasma amino acids did not occur in control subjects. Reduction in amino acid concentrations persisted until after the lysis of fever and did not coincide in timing with alterations in white blood counts or serum Zn and Fe values. Urinary total nitrogen, urea, and alpha amino nitrogen were not altered during the course of sand fly fever in these subjects. Although food intake was reduced during sand fly fever, the magnitude of the amino acid depression was far greater than that reported during starvation or protein deprivation in non-infected subjects, and the sequence of changes in plasma valine, alanine, and glycine followed patterns different from those reported during starvation. It may be postulated that unusually large quantities of certain plasma amino acids were taken up by the cells of the liver and other visceral tissues during this infection. Plasma phenylalanine responded in a manner different from that of the other amino acids. It was decreased on day 2 after exposure to the virus but by day 4 and 5 was significantly increased above preinfection values. This resulted in a significant increase in the phenylalaninetyrosine ratio during the febrile phase of sand fly fever.

Glucose homeostasis in viral hepatitis.

Abstract Fasting hypoglycemia (plasma glucose level below 60 mg per 100 ml) was observed in eight of 15 consecutive patients with acute viral hepatitis. Plasma insulin levels were decreased 30 per cent in the eight hypoglycemic patients. The plasma glucose response to glucagon was 1/3 that of normal controls, and was not improved by a high-carbohydrate diet. In normal subjects, glucagon elicited a prompt reduction in plasma amino acid levels that was greatest for alanine and glycine. No consistent reduction in amino acid concentration after glucagon administration was observed in the hepatitis group. Liver glycogen content, determined histologically, was markedly reduced in the patients with hepatitis. Acute viral hepatitis results in serious impairment in hepatic glycogen synthesis and gluconeogenesis and frequently gives rise to fasting hypoglycemia.

Essential amino acids in mature human milk.

Summary1. Results are presented from analyses of 147 samples of mature human milk from healthy mothers for nitrogen and 10 essential amino acids. The samples consisted of 18 collections from 5 women of all milk secreted in 24-hour periods and 129 collections from 56 women of milk secreted in periods of 4-8 hours. Mean values for concentrations of the amino acids in the 2 groups of samples agreed well. 2. Wide individual variations were found among successfully nursing women and at different intervals postpartum. Mean concentrations of nitrogen and the essential amino acids in 24-hour samples of colostrum, transitional, and mature milk showed a general lowering to the levels in mature milk as lactation was established and application of the Analysis of Variance to the data for 11 women, each of whom provided a sample during the same postpartum interval of mature milk production also indicated a gradual reduction in amino acid concentrations.