SAA Ratio Research Articles

Enhancement of ocular anti-glaucomic activity of agomelatine through fabrication of hyaluronic acid modified-elastosomes: formulation, statistical optimisation, in vitro characterisation, histopathological study, and in vivo assessment

Aim The aim of this manuscript was to fabricate agomelatine (AGM) loaded elastosomes to improve its corneal permeation and ocular bioavailability. AGM is a biopharmaceutical classification system (BCS) class II with low water solubility and high membrane permeability. It has a potent agonistic action on melatonin receptors, so it is used for glaucoma treatment. Methods Elastosomes were made using modified ethanol injection technique according to a 22 × 41 full factorial design. The chosen factors were: edge activators (EAs) type, surfactant percent (SAA %w/w), and cholesterol:surfactant ratio (CH:SAA ratio). The studied responses were encapsulation efficiency percent (EE%), mean diameter, polydispersity index (PDI), zeta potential (ZP), percentage of drug released after two hours (Q 2h%), and 24 hours (Q 24h%). Results The optimum formula with the desirability of 0.752 was composed of Brij98 as EA type, 15%w/w SAA%, and 1:1 CH:SAA ratio. It revealed EE% of 73.22%w/v and mean diameter, PDI, ZP, Q 2h%, and Q 24h% values of 484.25 nm, 0.31, −30.75 mV, 32.7%w/v, and 75.6%w/v, respectively. It demonstrated acceptable stability for three months and superior elasticity than its conventional liposome. The histopathological study ensured the tolerability of its ophthalmic application. Also, it was proven to be safe from the results of the pH and refractive index tests. The in vivo pharmacodynamic parameters of the optimum formula revealed dominance in a maximum % decrease in intraocular pressure (IOP), the area under the IOP response curve, and mean residence time with the value of 82.73%w/v, 820.69%h, and 13.98 h compared to that of the AGM solution (35.92%w/v, 181.30%h, and 7.52 h). Conclusions Elastosomes can be a promising option to improve AGM ocular bioavailability.

16 Sulfur amino acid utilization during immune system stimulation in growing pigs

Abstract Immune system stimulation (ISS) modifies protein and amino acid (AA) metabolism in animals and humans. During ISS, AA are redirected away from growth and reproduction towards mounting an immune response. This redirection can impact AA requirements both qualitatively (i.e., the AA ratio) and quantitatively. Special attention has been given to sulfur-containing amino acid (SAA; Met + Cys) metabolism during ISS, due to their roles as precursors for the synthesis of proteins and metabolites that are involved in the immune response. A series of studies were conducted to investigate the impact of ISS on various aspects of SAA utilization, including ileal digestibility, plasma kinetics, the glutathione (GSH) synthesis rate, the irreversible loss of Cys, and dietary total SAA requirements. In all of the studies, pigs were feed restricted (≥ 2 times the maintenance requirement for ME) to eliminate the confounding effect of ISS on feed intake. Results indicated that ISS alters SAA metabolism and increases SAA requirements per unit of protein deposition. The latter occurs due to increased maintenance requirements for SAA during ISS. The results also showed that the enhanced maintenance requirement for SAA occurs mainly as a result of increased SAA utilization, mainly Cys, for the synthesis of immune system metabolites, such as GSH and acute-phase proteins, as well as the increased catabolism of Cys to taurine. In addition, we found that ISS increases the dietary Met-to-total SAA ratio in pigs, suggesting an enhanced preferential demand for dietary Met during ISS, perhaps to support an elevated rate of transsulfuration. Collectively, our findings point toward a need for developing an optimal dietary AA profile for diseased pigs.

Imbalanced dietary methionine-to-sulfur amino acid ratio can affect amino acid profiles, antioxidant capacity, and intestinal morphology of piglets.

Animal protein sources such as fishmeal and plasma powder are excellent and indispensable sources of energy, amino acids, and minerals in animal production. Amino acid imbalance, especially methionine-to-sulfur amino acid (Met:SAA) ratio, caused by an imbalance of animal protein meal leads to growth restriction. This study was conducted to evaluate the effects of imbalanced Met:SAA ratio supplementation of different animal protein source diets on growth performance, plasma amino acid profiles, antioxidant capacity and intestinal morphology in a piglet model. Twenty-four weaned piglets (castrated males; BW = 10.46 ± 0.34 kg), assigned randomly into 3 groups (8 piglets/group), were fed for 28 d. Three experimental diets of equal energy and crude protein levels were as follows: 1) a corn-soybean basal diet with a Met:SAA ratio at 0.51 (BD); 2) a plasma powder diet with a low Met:SAA ratio at 0.41 (L-MR); 3) a fishmeal diet with a high Met:SAA ratio at 0.61 (H-MR). Results revealed that compared to BD, L-MR significantly decreased (P < 0.05) the activities of plasma total antioxidant capacity and glutathione peroxidase, plasma amino acid profiles, and significantly reduced (P < 0.05) villus height and crypt depth in the duodenum and jejunum. Additionally, L-MR significantly reduced (P < 0.05) the mRNA expression level of solute carrier family 7 member 9 (SlC7A9) in the ileum, and significantly increased (P < 0.05) mRNA expression levels of zonula occludens-1 (ZO-1) in the duodenum, and Claudin-1, ZO-1, sodium-coupled neutral amino acid transporters 2 (SNAT2) and SlC7A7 in the jejunum. H-MR significantly increased (P < 0.05) plasma SAA levels, and significantly reduced (P < 0.05) average daily feed intake, villus height, and villus height-to-crypt depth (VH:CD) ratio in the ileum compared to BD. In conclusion, L-MR may result in oxidative stress and villous atrophy but proves beneficial in improving intestinal barrier function and the activity of amino acid transporters for compensatory growth. H-MR may impair intestinal growth and development for weaned piglets. The research provides a guidance on the adequate Met:SAA ratio (0.51) supplementation in diet structure for weaned piglets.

Evaluation of various sulphur amino acid to lysine ratio for growing-finishing pigs fed antibiotic-free diets

This 10 wk feeding trial was conducted to determine the effect of increasing the standardised ileal digestible (SID) sulphur amino acid to lysine ratio (SAA:Lys) on performance and intestinal health parameters in growing-finishing (50–100 kg) pigs fed antibiotic-free diets. A total of 96 pigs [(Landrace × Yorkshire) × Duroc] with an average initial body weight (BW) of 52.2 ± 2.32 kg were randomly assigned to 4 dietary treatments each with 6 replicates (4 pigs per pen, 2 females and 2 males). The dietary treatments were 4 graded levels of SID SAA to Lys ratios (0.57, 0.67, 0.70 and 0.73). During the phase 1 (50–75 kg), pigs fed diets with increasing dietary SID SAA:Lys tended to improve the ADG (linear, p = .07) and G:F (linear, p = .06). During the phase 2 (75–100 kg), increasing SID SAA:Lys ratio had a tendency (linear, p = .08) to improve the ADG and G:F. Furthermore, the villus-to-crypt ratio of duodenum were linearly increased (p < .05) by increasing SID SAA:Lys at the end of the experiment. Moreover, increasing SID SAA:Lys ratio linearly improved (p < .05) the ratio of faecal Lactobacillus:Escherichia coli in both phase 1 and phase 2. There was a linear decrease (p < .05) in ammonia when pigs were fed diets with increased SID ratio of SAA:Lys in both phase 1 and phase 2. In conclusion, increasing the dietary SID SAA:Lys provided beneficial effect on gut health of growing-finishing pigs fed antibiotic-free diets and showed partial positive effect in growth performance.

Correlation Between Salivary Alpha-Amylase Level and Heart Rate Variability in Pediatric Subjects with Sleep-Disordered Breathing

Background and Objectives: The aim of this study was to evaluate the relationship between salivary alpha-amylase (sAA) and heart rate variability (HRV) indices in SDB children based on objective parameters of polysomnography (PSG). Materials and Method: This prospective study enrolled 67 children who underwent a physical examination and full-attended in-lab PSG with continuous electrocardiographic signal. The sAA were measured at night before PSG and in the early morning after PSG. Results: The subjects were divided into control [n=26, apnea-hypopnea index (AHI)≤1] and obstructive sleep apnea syndrome (OSAS, n=41, AHI＞1) groups; the OSAS group was subdivided into mild (1＜AHI≤5), moderate (5＜AHI≤10), and severe (10＜AHI) groups. The severe OSAS group was significantly different from the control and other OSAS subgroups in terms of the ratio between the low- and high-frequency components (LF/HF ratio) among the HRV indices. The LF/HF ratio was positively correlated with the sAA ratio and sAA subtraction (r=0.271; r=0.347). Conclusion: TAlthough both HRV and sAA were useful methods of predicting severe OSAS in children, a weak correlation between HRV and sAA was shown in pediatric OSAS subjects. Therefore, HRV and sAA may be independent parameters revealing different aspects of pediatric OSAS.

Attenuated acute salivary α-amylase responses to gustatory stimulation with citric acid in thin children.

Salivary α-amylase (sAA) is responsible for the 'pre-digestion' of starch in the oral cavity and accounts for up to 50% of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children.

A novel method to estimate changes in stress-induced salivary α-amylase using heart rate variability and respiratory rate, as measured in a non-contact manner using a single radar attached to the back of a chair

The authors have developed a non-contact system which estimates changes in salivary α-amylase (sAA ratio) induced by stress. Before and after stressful sound exposure, a single 24 GHz compact radar which is attached to the back of a chair measures the low frequency (LF) component of heart rate variability and respiratory rate, α-amylase in the subjects’ buccal secretions was measured by using an α-amylase assay kit. Using multiple regression analysis, sAA ratio was estimated using stress-induced LF change (LF ratio) and stress-induced respiratory rate change (respiratory rate ratio). Twelve healthy subjects were tested (12 males, 22 ± 2 years), who were exposed to audio stimuli with a composite tone of 2120 Hz and 2130 Hz sine waves at a sound pressure level of 95 dB after a silent period through a headphone. The result showed that sAA ratio estimated using multiple regression analysis significantly correlated with measured sAA ratio (R = 0.76, p < 0.01). This indicates that the system may serve for a stress management in the future.

Diurnal patterns of salivary alpha-amylase and cortisol secretion in female adolescent tennis players after 16 weeks of training

We examined the effects of 16 weeks of training on diurnal pattern of salivary alpha-amylase (sAA), cortisol, and the ratio of sAA over cortisol (AOC) in 12 national adolescent female tennis players. Stress and recovery were also evaluated using the Recovery-Stress-Questionnaire for Athletes-RESTQ-Sport. Data were collected after a 2-week rest (January, W0), and 4 months after W0 (W16). Subjects collected five saliva samples throughout a day. While all participants displayed the previously shown decrease after awakening in adolescents at W0, they showed a rise in the alpha-amylase awakening response and a higher alpha-amylase activity output (p<0.01) at W16 compared to W0. For the daily rhythm of cortisol we found subjects having a low overall output of salivary cortisol (p<0.01) and a blunted response to awakening at W16. Furthermore, an increase in the ratio AOC at W16, and a negative correlation between this ratio and Sport-specific recovery score. Our findings offer support for the hypothesis that increase of training load during the study period induced asymmetry activation between the two stress systems, in relation to psychological alterations and performance decrease. These results provide encouragement to continue exploring the impact of training program using a psychobiological approach among young athletes in order to prevent fatigue and preserve the health of these athletes.

The salivary alpha amylase over cortisol ratio as a marker to assess dysregulations of the stress systems

Different factors have been associated with changes in the regulation of the two major stress response systems of the human body, the sympathetic nervous system (SNS) and the hypothalamic–pituitary–adrenal (HPA) axis. Changes in these systems have been associated with various (psycho)pathologies across adulthood, and are thus frequently assessed within the context of allostatic load. Early Life Adversity (ELA) has been identified as one such factor. Individuals with histories of ELA show evidence of elevated basal and reactive salivary alpha amylase (sAA) levels (a marker of SNS activity), blunted cortisol levels (a marker of HPA axis activity), and an asymmetrical relationship between the two variables. However, variable methods used in the past to measure each variable, and the relationship between the two systems, prevent us from drawing firm conclusions.This preliminary study investigated whether the ratio of reactive sAA over reactive cortisol would be more informative to investigate the relationship between the two stress systems than the ratio of cortisol over sAA, or either marker alone, and whether there is a systematic link between this marker and subjective indexes of chronic stress and depression. We studied this in a total of 37 subjects (n=20 with signs of early life adversity and n=17 without) exposed to the Trier social stress test. Using a specific formula to determine the ratio of sAA over cortisol, we found a systematically stronger positive relationship with indexes of chronic stress and depression when compared to cortisol over sAA, or either marker alone. Our findings suggest that the ratio of sAA over cortisol might be a better marker of stress systems dysregulation than the ratio of cortisol over sAA, sAA or cortisol alone. The usefulness of this marker for other chronic stress states as found in allostatic load is discussed.

Use of the Ideal Protein Concept for Precision Formulation of Amino Acid Levels in Broiler Diets

Ideal amino acid ratios for chicks during the early growth period (0 to 21 days) are well documented by empirical evidence, but suggested ratios for older birds are in need of confirmation. Based on best empirical estimates of lysine, SAA, and threonine requirements of broiler chicks during 0 to 21, 21 to 42, and 42 to 56 days of age, together with new knowledge of maintenance contributions to the total requirement for these amino acids, it appear that the ideal ratio of SAA and threonine to lysine may change very little as birds advance in age and weight toward a 56-day market weight. This paper presents regression equations that predict both digestible and total lysine, SAA, and threonine requirements at any age or weight between hatching and 56 days.