Effects of porcine somatotropin administration on the responses to dietary lysine and a near-ideal blend of amino acids on the amino acid composition of whole-body protein and amino acid accretion rate in growing pigs.

An experiment was conducted to assess the effects of porcine somatotropin (pST) on the responses to a near-ideal blend of AA on the AA composition of empty, whole-empty body (WEB) protein and WEB essential AA accretion rate in pigs from 22 to 60 kg BW. Forty Hampshire × Yorkshire gilts were individually penned and assigned to a 4 × 2 factorial arrangement of treatments consisting of four diets with and without pST injection. A fortified corn-soybean meal basal diet was formulated to contain 1.50% total Lys with Thr, Met, and Trp added to obtain a near-ideal blend of these AA relative to Lys. In three additional diets, Lys was reduced to 1.25%, 1.00%, and 0.75% by diluting the basal diet with cornstarch, cellulose, and sand such that the diets also contained the same ratios of AA. Pigs that received pST were administered a daily i.m. injection of 2 mg of pST. At 60 kg BW, the WEB (carcass, head, viscera, blood, nails, and hair) was ground and analyzed for proximate and AA composition. Administration of pST increased (P < 0.001) accretion rates of WEB protein and essential AA. Increasing dietary essential AA increased (quadratic, P < 0.03) accretion rate of WEB protein, His, Leu, Trp, and Val in pST-treated pigs, but not in untreated pigs. Lysine composition in the accreted WEB protein was not affected (P > 0.05) by dietary Lys. The efficiency of Lys utilization for WEB Lys accretion was linearly affected (P < 0.01) by dietary Lys. These results indicated that the dietary Lys needed to achieve maximum WEB Lys accretion is markedly increased by pST administration.

This study evaluated the effects of two factors, porcine somatotropin and graded levels of amino acids, on the total accumulation and the accretion rate of amino acids across a broad range of protein deposition rates in growing pigs. Treatments included 1) with or without a daily injection of porcine somatotropin and 2) graded levels of total dietary lysine from 0.75% to 1.50%. As expected, both the administration of porcine somatotropin and increased dietary lysine increased both the amount and the rate of amino acid accretion. However, the amount and rate of amino acid accretion from increased dietary amino acids were markedly greater in pigs treated with porcine somatotropin. Thus, the extent to which the genetic potential for protein deposition is achieved depends on both the anabolic capacity of the pig and the amino acid concentration of the diet provided.

Effects of a manganese complex with lysine and glutamic acid on growth performance, manganese deposition, and emission, antioxidant capacity and metacarpal strength in weaned piglets.

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ±â€…0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.

This research explored the effects of a manganese complex containing lysine and glutamic acid (Mn-LG) on various health parameters in weaned piglets. Utilizing samples of 288 piglets, the study investigated how Mn-LG supplementation influences growth performance, Mn deposition and emission, antioxidant capacity, and metacarpal strength. Key findings include an increase in serum Mn levels and Mn superoxide dismutase (Mn-SOD) activity, a reduction in diarrhea incidence, and no significant effects in bone strength indices in piglets receiving Mn-LG. Additionally, the fecal Mn concentration was notably lower in the Mn-LG group than in the group receiving inorganic Mn at equivalent dosages.

Dietary Lysine Requirements of Older Adults Stratified by Age and Sex.

BACKGROUND: Current recommendation for lysine in older adults, 30 mg/kg/d, is based on young adult data. Evidence suggests that amino acid requirements may differ between young and old adults with both sex and age having an effect in the elderly. OBJECTIVES: This study aimed to define the lysine requirements in healthy older adults using the indicator amino acid oxidation (IAAO) method with L-[1-13C] phenylalanine as the indicator and to compare the derived estimates based on age: 60-69 y and >70 y. METHODS: Fourteen healthy males and 16 healthy females [>60 y, body mass index (BMI) = 26.3 kg/m2] were randomly assigned to receive 3-7 lysine intakes from 10 to 80 mg/kg/d. Subjects were adapted to a standard liquid diet providing 1.0 g/kg/d protein and adequate energy, for 2 d, with indicator oxidation measurements performed on day 3. The rate of release of 13CO2 from the oxidation of L-[1-13C] phenylalanine was measured in breath. A 2-phase linear mixed-effect model, and parametric bootstrap were used to determine mean lysine requirements and the 95% confidence intervals (CIs). The overlap of the 95% CI between the 2 age groups were used to compare the requirement estimates. The null hypothesis was accepted if the interval contained zero. RESULTS: The mean and upper 95% CI of the lysine requirement for females were 32.9 and 40.9 and 46.2 and 53.7 mg/kg/d for those aged 60-69 y and >70 y, respectively. The mean and upper 95% CI of the lysine requirement for the 2 groups of males were not different so was combined to yield a mean and 95% CI of 32.2 and 38.2 mg/kg/d. CONCLUSIONS: To our knowledge, this is the first study to report on the lysine requirement in adults aged >60 y. These results provide a basis from which the adequacy of diets to meet lysine needs of older adults can be assessed. The trial was registered at clinicaltrials.gov as NCT02008955 (https://clinicaltrials.gov/study/NCT02008955).

The standardized ileal digestible lysine-to-net energy ratio in the diets of sows to optimize milk nitrogen retention is dynamic during lactation.

Fifty-two multiparous sows (average parity 3.1 ±â€…0.9 and initial BW 245.6 ±â€…32.5 kg) were used to evaluate the effects of dietary standardized ileal digestible (SID) Lys-to-net energy (NE) ratios on nitrogen (N) utilization throughout a 24-d lactation period. Sows were randomly assigned to one of five isoenergetic feeding programs that provided equally spaced and increasing SID Lys-to-NE ratios between 2.79 and 5.50 g SID Lys/Mcal NE. The feeding programs were generated by blending the two extreme diets in varying proportions and were provided to sows immediately after farrowing (day 1) and until weaning at day 24 ±â€…1. Nitrogen balances were conducted between days 4 and 7, 12 and 15, and 20 and 23 ±â€…1 of lactation to represent weeks 1, 2, and 3, respectively, using total urine collection and fecal grab sampling. Contrast statements were used to determine the linear and quadratic effects of increasing Lys-to-NE ratios. Linear and quadratic broken-line and polynomial quadratic (QPM) models were used to determine the optimum dietary Lys-to-NE ratios for N retention in milk. The Bayesian information criterion was used to assess the best fit. Feeding program did not influence sow average daily feed intake (5.8 ±â€…0.1 kg), BW change (-8.2 ±â€…3.1 kg), or change in back fat thickness (-2.6 ±â€…0.7 mm) over the 24-d lactation period, but piglet average daily gain increased with dietary SID Lys-to-NE ratio (linear; P < 0.05). Sow N intake increased with increasing dietary Lys-to-NE ratio in weeks 2 and 3 (linear; P < 0.001). Whole-body N retention (N intake - N output in urine and feces) increased with increasing dietary Lys-to-NE ratio in all weeks (linear; P < 0.05). The N retention in milk tended to increase then decrease with increasing dietary Lys-to-NE ratio in weeks 1 and 2 (quadratic; P = 0.051 and P = 0.081) and the QPM showed optimal milk N retention at 4.28, 4.42, and 4.67 g Lys/Mcal NE for weeks 1, 2, and 3, respectively. Maternal N retention (N intake - N output in urine, feces, and milk) decreased and then increased in week 1 (quadratic; P < 0.01) and increased in weeks 2 and 3 (linear; P < 0.01) with increasing dietary Lys-to-NE ratio. Therefore, the SID Lys-to-NE ratio necessary to optimize milk N output is dynamic throughout lactation. A two-diet feeding program could be created to match optimal weekly or daily SID Lys-to-NE ratios, which could lead to improved piglet ADG and body weights at weaning.

Despite significant changes in nutrient and energy requirements as well as voluntary feed intake during lactation, sows are typically fed a single diet with a static nutrient and energy composition throughout the entire lactation period, which may not optimize milk output. Fifty-two sows were used to explore how various ratios of standardized ileal digestible (SID) Lys to net energy (NE) in lactating sow diets affect the growth of piglets and nitrogen utilization during a 24-d lactation period. Sows were randomly assigned to one of five feeding programs that contained equal amounts of energy and provided equally spaced and increasing Lys-to-NE ratios between 2.79 and 5.50 g SID Lys/Mcal NE immediately after farrowing. The dietary Lys-to-NE ratio did not influence sow daily feed intake, body weight change, or change in backfat thickness over the 24-d lactation period; however, piglet growth rate and body weight at weaning increased with increasing Lys-to-NE ratio. The SID Lys-to-NE ratio necessary to optimize milk nitrogen output was 4.28, 4.42, and 4.67 g SID Lys/Mcal NE during weeks one, two, and three of lactation, respectively. Therefore, it is possible to create a two-diet feeding program offering dynamic SID Lys-to-NE ratios as lactation progresses, which could lead to improved piglet average daily gain and body weights at weaning.

The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA).

BACKGROUND AND AIMS: The cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification. METHODS AND RESULTS: We investigated the association between 2-AAA and dietary nutrient intake in a cross-sectional study of healthy individuals (N = 254). We then performed a randomized cross-over dietary intervention trial to investigate the effect of lysine supplementation (1 week) on 2-AAA in healthy individuals (N = 40). We further assessed the effect of a vegetarian diet on 2-AAA in a short-term (4-day) dietary intervention trial in healthy omnivorous women (N = 35). We found that self-reported dietary intake of animal products, including meat, poultry, and seafood, was associated with higher plasma 2-AAA cross-sectionally (P < 0.0001). Supplementary dietary lysine (5g/day) caused no significant increase in plasma 2-AAA; however, plasma 2-AAA was altered by general dietary modification. Further, plasma 2-AAA was significantly reduced by a short-term vegetarian diet (P = 0.003). CONCLUSION: We identified associations between plasma 2-AAA and consumption of animal products, which were validated in a vegetarian dietary intervention trial, but not in a trial designed to specifically increase the 2-AAA amino acid precursor lysine. Further studies are warranted to investigate whether implementation of a vegetarian diet improves cardiometabolic risk in individuals with elevated 2-AAA.

Co-administration of "L-Lysine, Vitamin C, and Zinc" increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats.

PURPOSE: We previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. METHODS: The streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. RESULTS: The determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. CONCLUSIONS: The results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.

Morphometric analysis of the effects of high molecular weight sodium hyaluronate and amino acids mixture on face rejuvenation.

BACKGROUND: Skin aging can be observed at various levels in the epidermis, dermis, and dermo-epidermal junction. Reducing the cosmetic effects of skin aging in the facial region is a widespread demand due to common aesthetic concerns. Consequently, many injectable products on the market promise antiaging effects and cosmetic improvements. We aimed to evaluate the cosmetic efficacy of a high molecular weight sodium hyaluronate and amino acids mixture for the facial region using morphometric analysis. METHODS: This study evaluates the morphometric effectiveness of an injectable mixture (high molecular weight sodium hyaluronate, glycine, L-Proline, L-leucine, L-lysine HCL, L-valine, and L-alanine collagen active ingredient) on the mid-face and jawline in women aged 30-55. We used morphological measurements and digital image data to assess changes and determine effectiveness. Various computational methods were applied simultaneously with statistical tests for validation. RESULTS: The hydration assessment showed a significant increase on both sides of the face. A noticeable decrease was observed in gonion angle, bitragion breadth, bigonion breadth, and marionette wrinkle scale. These results suggest combining mechanical and chemical stimulation from the injection and its components (hyaluronic and amino acids) effectively enhances skin quality. CONCLUSIONS: The study indicates that the mechanical stimulation of the injection improves skin quality. Combining hyaluronic and amino acids (collagen, elastin, and pro-synthetic) is a safe and effective alternative for antiaging treatments.

Effect of dietary electrolyte balance and arginine to lysine ratio on hematological, antioxidant and immunological traits in dual-purpose breeding hens under cyclic heat stress condition.

A total of 245 hens and 35 cocks (32 weeks age) were assigned to seven treatment groups (five replicates with seven hens and one cock) to investigate the effect of dietary electrolyte balance (DEB) and arginine to lysine ratio (Arg/Lys) on birds' physiological and biochemical traits under cyclic heat stress (CHS) condition. Birds were housed in an environmentally controlled facility having four sectors. The first group (positive control, PC) was kept under thermoneutral conditions and fed diet with DEB of 180 mEq and Arg/Lys of 1.25, whereas the other six treatments were kept in the second sector under CHS and fed diet with DEB and Arg/Lys equal to: 180 mEq and 1.25 (negative control, NC); 250 mEq and 1.25; 320 mEq and 1.25; 180 mEq and 1.37; 250 mEq and 1.37; 320 mEq and 1.37, respectively. Hens on NC group had significantly decreased red blood cells (RBCs), white blood cells (WBCs) and its fractions. The groups fed different DEB and Arg/Lys in diet significantly enhanced the blood parameters and plasma lipid profile compared NC group. Hens under CHS fed on 250 and 320 DEB with 1.37 Arg/Lys recorded the lowest concentration of low-density lipoprotein (LDL) compared with the other groups. Triiodothyronine (T3) activity was not differed among groups, while T4 activity in layer exposed to CHS (NC group) recorded the highest activity compared to PC. From findings, it can be concluded that laying hens fed a diet having DEB 250 mEq with 1.37 Arg/Lys could be successfully applied to counteract the adverse effect of CHS and to improve blood hematological and biochemical traits, antioxidants, and immunity response.

Clinical Reasoning: Pediatric Seizures of Unknown Cause.

We describe a neonate and a 14-month-old child presenting with seizures that were not (completely) controlled with antiepileptic medications. There were no signs of infection, and electrolytes and neuroimaging were normal. In the neonate, pyridoxine was administered followed by cessation of seizures, and a diagnosis of pyridoxine-dependent epilepsy (PDE-ALDH7A1, a neurometabolic disorder of lysine metabolism) was genetically confirmed. The 14-month-old child received a genetic diagnosis of PDE-ALDH7A1 after abnormalities in the metabolic investigations. Both children were treated with pyridoxine and adjunct lysine reduction therapy (LRT). Seizures were controlled completely, but both children are developmentally delayed. During her second pregnancy, the mother of the neonate was started on pyridoxine treatment because of the risk of PDE-ALDH7A1. After delivery, pyridoxine treatment was continued in the neonate, who did not show any clinical symptoms. Molecular analysis identified the familial variants consistent with the diagnosis of PDE-ALDH7A1. Adjunct LRT was initiated. This child has never experienced seizures, and development has been completely normal thus far (age 2.9 years), despite the shared genotype with their sibling with developmental delays (DDs). In conclusion, in neonates, infants, and children presenting with seizures of unknown origin with partial or no response to common antiepileptic medications, the diagnosis of PDE-ALDH7A1 or other pyridoxine-responsive genetic epilepsies should be considered, prompting a trial of pyridoxine as "diagnostic therapeuticum." The digital application Treatable-ID (treatable-id.org) can support clinicians in the early diagnosis of treatable conditions in patients presenting with DD/intellectual disability of unknown cause.

Habitual intake of dietary advanced glycation end products is not associated with generalized microvascular function-the Maastricht Study.

BACKGROUND: Endogenously formed advanced glycation end products (AGEs) may be important drivers of microvascular dysfunction and the microvascular complications of diabetes. AGEs are also formed in food products, especially during preparation methods involving dry heat. OBJECTIVES: We aimed to assess cross-sectional associations between dietary AGE intake and generalized microvascular function in a population-based cohort. METHODS: In 3144 participants of the Maastricht Study (mean ± SD age: 60 ± 8 y, 51% men) the dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of our ultra-performance LC-tandem MS dietary AGE database and an FFQ. Microvascular function was determined in the retina as flicker light-induced arteriolar and venular dilation and as central retinal arteriolar and venular equivalents, in plasma as a z score of endothelial dysfunction biomarkers (soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1, soluble E-selectin, and von Willebrand factor), in skin as the heat-induced skin hyperemic response, and in urine as 24-h albuminuria. Associations were evaluated using multiple linear regression adjusting for demographic, cardiovascular, lifestyle, and dietary factors. RESULTS: Overall, intakes of CML, CEL, and MG-H1 were not associated with the microvascular outcomes. Although higher intake of CEL was associated with higher flicker light-induced venular dilation (ß percentage change over baseline: 0.14; 95% CI: 0.02, 0.26) and lower plasma biomarker z score (ß: -0.04 SD; 95% CI: -0.08, -0.00 SD), the effect sizes were small and their biological relevance can be questioned. CONCLUSIONS: We did not show any strong association between habitual intake of dietary AGEs and generalized microvascular function. The contribution of dietary AGEs to generalized microvascular function should be further assessed in randomized controlled trials using specifically designed dietary interventions.

Exposure of Caenorhabditis elegans to Dietary Nε-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products.

The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, Caenorhabditis elegans. Dietary bacteria were chemically modified with glyoxylic acid to mainly produce Nε-carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms' intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs.

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system.

We tested the hypothesis that ethanol would aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) sepsis in the cardiorenal system and that inhibition of inducible nitric oxide synthase (iNOS) would prevent such response. Male C57BL/6 mice were treated with ethanol for 12 weeks. One hour before SL-CLP surgery, mice were treated with N6-(1-iminoethyl)-lysine (L-NIL, 5 mg/kg, i.p.), a selective inhibitor of iNOS. A second dose of L-NIL was administered 24 h after SL-CLP surgery. Mice were killed 48 h post surgery and the blood, the renal cortex, and the left ventricle (LV) were collected for biochemical analysis. L-NIL attenuated the increase in serum creatinine levels induced by ethanol, but not by SL-CLP. Ethanol, but not SL-CLP, increased creatine kinase (CK)-MB activity and L-NIL did not prevent this response. In the renal cortex, L-NIL prevented the redox imbalance induced by ethanol and SL-CLP. Inhibition of iNOS also decreased lipoperoxidation induced by ethanol and SL-CLP in the LV. L-NIL prevented the increase of pro-inflammatory cytokines and reactive oxygen species induced by ethanol and (or) SL-CLP in the cardiorenal system, suggesting that iNOS modulated some of the molecular mechanisms that underlie the deleterious effects of both conditions in the cardiorenal system.

The effect of ketoprofen lysine salt on mucosa of rat stomach after ethyl alcohol intoxication.

INTRODUCTION: Ketoprofen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Side effects of ketoprofen occur mainly from the gastrointestinal tract due to the inhibition of cyclooxygenaze-1. Binge drinking at least once a week is reported by 80 million Europeans. On the day after many of them use NSAIDs. This increases the risk for damage of gastric mucosa. AIM: The aim of the study was to check if use of ketoprofen lysine salt (KLS) has any gastroprotective effect on mucosa of rat stomach after ethyl alcohol intoxication. MATERIALS AND METHODS: There were 6 groups of 6 male rats which received: RESULTS: In groups 1, 2 and 3 the histopathologic examination of the stomachs revealed normal picture, without signs of inflammation. In the group 4, 5 and 6 within the mucosa and submucosa there were visible numerous infiltrates of inflammatory cells, consisting mainly of lymphocytes, plasmocytes and eosinophilia. Total leukocyte count was elevated in group 3, 4, 6. There was a significant decrease of blood urea concentration in group 6 vs 2 and significant decrease of serum albumin in group 6 vs 1 and 2, and total protein vs group 1. CONCLUSION: Side effects of ketoprofen occur mainly from the gastrointestinal tract. KLS has no gastroprotective effect after ethanol-gastric injury and does not protect gastric mucosa from damage produced by binge drinking. Therefore it should not be used after drinking distilled spirits.

Oral aspirin or low dose of intravenous lysine acetylsalicylate in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

AIM: To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI. METHODS: This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days. Pharmacodynamic analyses were performed at five time points: baseline, and 1, 2, 4 and 12 h after the loading dose, and measured as ASA reaction units (ARU) by the Verify Now System. An ARU more than 550 was considered as nonresponsiveness to study drugs. The primary end point was the different rate of patients with ARU more than 550 at 2 h after the loading dose of oral vs. intravenous ASA. Secondary end points included the comparison of ARU more than 550 at the other time points and the comparison of continuous ARU at each time point. RESULTS: The study was planned with a sample size of 68 patients, but it was prematurely stopped due to slow enrollment after the inclusion of 23 patients, 12 randomized to oral ASA and 11 to intravenous lysine acetylsalicylate. At 2 h the rate of patients with ARU more than 550 was numerically but not significantly higher in patients receiving oral ASA as compared with intravenous lysine acetylsalicylate (33 vs. 14.2%; Δ -0.19, 95% confidence interval -0.59-0.21, P = 0.58). The difference over time was NS (P = 0.98), though the prevalence of ARU more than 550 was higher at the other time points. Both routes of administration reduced ARU values over time, though with no overall significant difference between profiles (P overall = 0.48). CONCLUSION: In patients with STEMI undergoing pPCI the rate of nonresponsiveness to ASA was not different comparing an oral 'noncoated' loading dose of ASA with an intravenous bolus injection of lysine acetylsalicylate. However, as patient enrollment was prematurely terminated, this study is underpowered to draw a definite conclusion.

Effects of low-crude protein diets supplemented with rumen-protected lysine and methionine on fattening performance and nitrogen excretion of Holstein steers.

The objective of this experiment was to investigate the effects of low-crude protein (CP) diets supplemented with rumen-protected lysine and methionine on growth performance, nitrogen excretion, and carcass traits in Holstein steers. Steers consumed the following diets: (1) 17.2% CP on a dry-matter basis during the early period (from 7 to 10 months of age) and 14.5% CP during the late period (from 10 to 18 months of age; CON, n = 4, initial body weight [BW] 238 kg), and (2) 14.4% CP during the early period and 11.4% CP during the late period (AA, n = 4, initial BW 243 kg). The AA diet contains rumen-protected lysine and methionine. Except for CP intake, feed intake and body weight gain were not affected by dietary CP content. Total nitrogen excretion per metabolic BW tended to be lower (p < .10) in the early period and significantly lower (p < .05) in the late period with decreasing the feed CP content. Plasma urea nitrogen concentrations were lower in AA than CON. Carcass traits and total free amino acid contents of the longissimus thoracis muscle were not affected by dietary CP content. Adding rumen-protected lysine and methionine to a low-CP diet would reduce nitrogen excretion in fattening Holstein steers without affecting productivity.

Comparison of Nausea and Vomiting Associated With Amino Acid Formulations Coinfused With Peptide Receptor Radionuclide Therapy: Commercial Parenteral Nutrition Formulas Versus Compounded Arginine/Lysine.

OBJECTIVES: Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177Lu-DOTATATE. Our program transitioned to compounded l-arginine 2.5%/l-lysine 2.5% in 0.9% NaCl after commercial approval of 177Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations. METHODS: Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities. RESULTS: Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%). CONCLUSIONS: Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.

Monitoring PSMA Responses to ADT in Prostate Cancer Patient-Derived Xenograft Mouse Models Using [18F]DCFPyL PET Imaging.

PURPOSE: PSMA overexpression has been associated with aggressive prostate cancer (PCa). However, PSMA PET imaging has revealed highly variable changes in PSMA expression in response to ADT treatment ranging from increases to moderate decreases. To better understand these PSMA responses and potential relationship to progressive PCa, the PET imaging agent, [18F]DCFPyL, was used to assess changes in PSMA expression in response to ADT using genomically characterized LuCaP patient-derived xenograft mouse models (LuCaP-PDXs) which were found to be sensitive to ADT (LuCaP73 and LuCaP136;CS) or resistant (LuCaP167;CR). METHODS: [18F]DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) was used to assess PSMA in vitro (saturation assays) in LuCaP tumor membrane homogenates and in vivo (imaging/biodistribution) in LuCaP-PDXs. Control and ADT-treated LuCaPs were imaged before ADT (0 days) and 2-, 7-, 14-, and 21-days post-ADT from which tumor:muscle ratios (T:Ms) were determined and concurrently tumor volumes were measured (caliper). After the 21-day imaging, biodistributions and histologic/genomic (PSMA, AR) analysis were done. RESULTS: [18F]DCFPyL exhibited high affinity for PSMA and distinguished different levels of PSMA in LuCaP tumors. Post-ADT CS LuCaP73 and LuCaP136 tumor volumes significantly decreased at day 7 or 14 respectively vs controls, whereas the CR LuCaP167 tumor volumes were minimally changed. [18F]DCFPyL imaging T:Ms were increased 3-5-fold in treated LuCaP73 tumors vs controls, while treated LuCaP136 T:Ms remained unchanged which was confirmed by day 21 biodistribution results. For treated LuCaP167, T:Ms were decreased (~ 45 %) vs controls but due to low T:M values (<2) may not be indicative of PSMA level changes. LuCaP73 tumor PSMA histologic/genomic results were comparable to imaging/biodistribution results, whereas the results for other tumor types varied. CONCLUSION: Tumor responses to ADT varied from sensitive to resistant among these LuCaP PDXs, while only the high PSMA expressing LuCaP model exhibited an increase in PSMA levels in response to ADT. These models may be useful in understanding the clinical relevance of PSMA PET responses to ADT and potentially the relationship to disease progression as it may relate to the genomic signature.

Dietary Lysine Levels Improved Antioxidant Capacity and Immunity via the TOR and p38 MAPK Signaling Pathways in Grass Carp, Ctenopharyngodon idellus Fry.

An 8-week rearing trial was designed to appraise the dietary lysine levels on intestinal antioxidant capacity and immunity of grass carp fry. Six practical diets were prepared with graded levels of lysine (1.44, 1.79, 1.97, 2.44, 2.56 and 2.87% dry matter), and these diets were fed to grass carp fry. The results showed that the activities of intestinal antioxidant factors including catalase and glutathione peroxidase were markedly improved by the 2.44% dietary lysine compared with the control diet (1.44% dietary lysine) (P < 0.05). In terms of antioxidants, compared with the control diet, the 2.44% diet markedly upregulated the mRNA expression levels of target of rapamycin, S6 kinase1 and nuclear factor erythroid 2-related factor 2 pathway-related antioxidant genes, containing catalase and glutathione peroxidase 1α (P < 0.05) and downregulated the mRNA levels of Kelch-like ECH-associated protein 1 (P > 0.05). The mRNA levels of 4E-binding protein 2 showed the opposite trend compared with those of target of rapamycin, and the minimum value was observed in the group of 1.97% dietary lysine (P < 0.05). In terms of immunity, compared with the 1.44% diet, the 2.44% diet markedly suppressed the intestinal p38 mitogen-activated protein kinase and interferon γ2 mRNA levels (P < 0.05). Moreover, nuclear factor-kappa B p65, tumor necrosis factor α, interleukin 6, interleukin 8, and interleukin 15 mRNA levels all exhibited the same trend as p38 mitogen-activated protein kinase and interferon γ2; however, the difference among all the lysine treatments groups was not significant (P > 0.05). The anti-inflammatory cytokines transforming growth factor ß2 and interleukin 4/13B mRNA levels in the intestine were remarkably upregulated by high dietary lysine levels (2.56 and 2.87%) (P < 0.05), and when the dietary lysine level reached 2.44%, the interleukin 4/13A mRNA levels were strikingly increased (P < 0.05). Overall, the data suggested that 2.44% dietary lysine could strengthen the immune and antioxidant capacities of grass carp fry via activating the target of rapamycin (TOR) signaling pathway, and suppressing the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which then improve the survival rate.

Growth performance and accretion of selected amino acids in response to three levels of dietary lysine fed to fast- and slow-growing broilers.

Literature data indicate that feed intake is sensitive to the dietary Lys content particularly in fast-growing birds. From a conceptual and a practical viewpoint, an interaction between genotype (i.e., fast-growing vs. slow-growing birds) and dietary Lys content is of interest, but it needs confirmation owing to a dearth of studies addressing this issue. A study was conducted with 266 Cobb 500 birds and 266 Thai native crossbreed birds serving as models for fast-growing broilers (FGB) and slow-growing broilers (SGB), respectively. Within genotype, chicks were randomly allocated to diets containing either a high (H-LYS = 1.36%), medium (1.17%), or low Lys (1.01%) content. Growth performance and the accretion of protein and selected amino acids were determined in birds from 1 to 21 d of age. Treatments were arranged in a factorial design with 6 replications/treatment. Low Lys vs. H-LYS caused a 42.1% lower feed intake in FGB (P < 0.001), but not in SGB (P = 0.596). The feed conversion ratio (FCR (g feed/g BW gain)) was lowest in FGB (P < 0.001) and increased with decreasing dietary Lys contents (P < 0.001). The Lys induced increase in FCR, however, was more pronounced in SGB (P = 0.025). The absolute protein gain (g/bird) was influenced by the Lys content of feed and decreased by ∼54% and ∼23% in FGB and SGB, respectively (P < 0.001). The efficiency (% of intake) of protein accretion was found to be greater in FGB (P ≤ 0.001) and decreased with decreasing dietary Lys (P ≤ 0.001). The efficiency of Lys accretion was found to be negatively affected by the dietary Lys content in FGB (P < 0.001) but not SGB (Pgenotype × dietary Lys = 0.008). It can be concluded that a dietary Lys content of 1.01% does not safeguard both growth performance and body protein accretion efficiency in both FGB and SGB. The suboptimal growth performance in FGB, but not SGB, is partially counteracted by a Lys-induced reduction in feed intake.

Relative availability of metabolizable methionine from 2 ruminally protected sources of methionine fed to lactating dairy cattle.

Our objective was to evaluate the lactational responses of dairy cows to methionine provided from 2 ruminally protected sources of methionine activity. Twenty-one Holstein dairy cows [11 primiparous (634 kg of body weight, 140 d in milk) and 10 second-parity (670 kg of body weight, 142 d in milk)] were assigned to a treatment sequence in 4 replicated 5 × 5 Latin squares plus 1 cow, with 14-d periods. Treatments were as follows: control; 7.5 or 15 g/d of a ruminally protected product of 2-hydoxy-4-methylthio-butyric acid (NTP-1401; Novus International Inc., St. Charles, MO); or 7.5 or 15 g/d of a ruminally protected dl-methionine product (Smartamine M; Adisseo, Alpharetta, GA). The diet was predicted to meet metabolizable protein and energy requirements. Diets contained 16.1% crude protein, and the control diet was predicted to be deficient in metabolizable methionine (1.85% of metabolizable protein) but sufficient in lysine (6.8% of metabolizable protein). Feed intake and milk yield were measured on d 11 to 14. Blood was collected on d 14. Dry matter intake, milk yield, energy-corrected milk, milk fat yield and percentage, and efficiencies of milk and energy-corrected milk yield were not affected by treatment. Milk protein percentage and milk protein yield increased linearly with supplementation, without differences between methionine sources or interactions between source and level. Linear regressions of milk protein percentage and milk protein yield against supplement amount within source led to slope ratios (NTP-1401:Smartamine M) of 95% for protein percentage and 84% for protein yield, with no differences between sources for increasing milk protein. Plasma methionine concentrations were increased linearly by methionine supplementation; the increase was greater for Smartamine M than for NTP-1401. Plasma d-methionine was increased only by Smartamine M. Plasma 2-hydoxy-4-methylthio-butyric acid was increased only by NTP-1401. Our data demonstrated that supplementation with these methionine sources can improve milk protein percentage and yield, and the 2 methionine sources did not differ in their effect on lactation performance or milk composition.