Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Rescue therapy of early neurological deterioration in lacunar stroke.

BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Impact of dietary arginine supplementation on immune responses and growth performance in Newcastle disease virus-infected broiler chicks.

BACKGROUND: Newcastle disease (ND) poses significant challenges within the poultry industry, leading to increased mortality rates, compromised growth, weakened immunity and elevated levels of inflammation. OBJECTIVE: This study explores the potential of dietary arginine supplementation to ameliorate these adverse effects of ND, leveraging arginine's well-documented benefits in enhancing growth and immune responses. METHODS: A total of 480 one-day-old male broiler chicks were meticulously categorised into eight groups, encompassing both infected and noninfected cohorts. These chicks received diets with arginine levels at 85%, 100%, 125% and 150% of recommended standards. The study entailed a comprehensive examination of clinical manifestations, growth performance metrics, haemagglutination inhibition (HI) test results, and serum concentrations of proinflammatory cytokines, adrenocorticotropic hormone (ACTH), and cortisol (CORT). RESULTS: The infection significantly curtailed feed consumption (p = 0.0001) and weight gain (p = 0.0001) while concurrently depressing HI titres. Additionally, infected chicks experienced an exacerbated feed conversion ratio (p = 0.0001), escalated mortality rates (p = 0.0001), and elevated serum concentrations of proinflammatory cytokines (p = 0.0001), ACTH (p = 0.0001), and CORT (p = 0.0001). Remarkably, dietary arginine supplementation effectively mitigated the adverse impacts of ND infection on growth, immune responses and proinflammatory cytokine levels. In the context of ND infection, mortality rates and inflammation surge, while growth and immunity are significantly compromised. CONCLUSIONS: The strategic inclusion of arginine in the diet emerges as a potent strategy to counteract the deleterious effects of ND. Supplementation with arginine at levels exceeding the conventional dietary recommendations is recommended to alleviate the detrimental consequences of ND effectively.

Regulation of Neuropeptide Y Receptor Gene Expression and Hormone Level in Obese Male Rats Receiving 6-Gingerol and L-Arginine Supplementation.

Obesity and its associated disorders, such as hyperlipidemia, have become a global issue following the consumption of unhealthy, high-fat, and high- carbohydrate foods, which burdens the economies and the health systems of human societies worldwide. This study aimed to evaluate the effect of oral consumption of 6-gingerol and L-arginine supplements on obesity factors. Thirty rats in five groups were fed a diet specific to each group for 12 weeks and then treated with the oral administration of L-arginine (200 mg/day) and 6-gingerol (100 mg/day) for 12 weeks. The food and water intake and weight change, were then measured. In addition, plasma glucose, triglyceride, cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL) , low-density lipoprotein (LDL), and serum hormone levels, including corticosterone, testosterone, and insulin, were measured, and NPY, Y1, and Y5 receptor gene expression were recorded using real-time PCR. Administration of 6-gingerol and L-arginine decreased food intake, weight gain, glucose levels, insulin levels, and homeostasis model assessment-insulin resistance (HOMA-IR) index compared to the HCD control group. In addition, corticosterone and testosterone levels in the study groups showed a significant decrease (P<0.05) and increase (P<0.01) compared to the control groups, respectively. Triglyceride, total cholesterol, HDL, and VLDL levels in the groups treated with L-arginine and gingerol alone or combined significantly decreased compared to the control group (P<0.01). This study confirms that 6-gingerol and L-arginine supplements prevent HCD-induced hyperlipidemia by controlling hormones and neurotransmitters involved in the general metabolism. .

Effect of standardized ileal digestible arginine:lysine on growth performance of 6- to 13-kg nursery pigs.

A total of 480 newly weaned pigs (PIC 337 × 1050; Genus, Hendersonville, TN) with an initial body weight (BW) of 6.20 ±â€…0.61 kg were used in a dose-response study to investigate the impact of increasing standardized ileal digestible (SID) Arg:Lys on nursery pig growth performance. At weaning, pigs were placed into 48 pens with 5 barrows and 5 gilts per pen. Pens were randomly assigned to 1 of 6 dietary treatments. The experimental diets were formulated with increasing SID Arg:Lys, achieved by substituting corn starch, glycine, and l-alanine with l-arginine, resulting in SID Arg:Lys ranging from 45% to 145%. Diets were sublimiting in SID Lys and exceeded all other essential amino acid requirements. The experimental diets were fed across two feeding phases from days 0 to 10 and 10 to 27, with adjustments made to account for the Lys requirement of the pigs. All pens were placed on a common diet for the remaining 14 d of the study to evaluate carryover effects. Pigs and feeders were weighed at the start and end of each phase to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Data were analyzed according to a linear regression model, which included the linear and quadratic effects of SID Arg:Lys and initial BW. Pen was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.50 < P ≤ 0.10. From days 0 to 27, Arg:Lys tended to have a quadratic effect on ADFI (P = 0.058), where 97.00 ±â€…7.631% SID Arg:Lys maximized feed intake. Similarly, Arg:Lys had a quadratic impact on ADG (P = 0.046), where ADG was maximized at a SID Arg:Lys of 95.65 ±â€…7.165. Correspondingly, Arg:Lys had a quadratic effect on pig BW on day 27 (P = 0.014). These effects were carried through the end of the study, where Arg:Lys quadratically impacted days 0 to 41 ADFI (P = 0.006), ADG (P = 0.077), and day 41 BW (P = 0.028). There was no evidence of an effect of SID Arg:Lys on G:F throughout the study (P ≥ 0.315). In conclusion, SID Arg:Lys quadratically impacted ADFI and ADG in 6- to 13-kg nursery pigs, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]), and ADG was maximized at a SID Arg:Lys of 95.65% (95% CI [81.2%, 110.1%]). Together, these data suggest that the SID Arg:Lys requirement of nursery pigs is at least 81%, based on the lower bounds of the 95% CI for maximum ADG and ADFI, and excessive Arg supplementation may negatively affect growth performance.

Arginine is considered a conditionally essential amino acid (EAA) in swine, meaning that under certain circumstances, the rate of Arg utilization is greater than endogenous synthesis, resulting in a dietary Arg requirement to meet the pig's needs for growth and other biological functions. Our group and others have shown benefits to feeding Arg levels above the NRC (2012) estimated requirement; however, there has been a lack of research to determine the SID Arg requirement relative to lysine in young pigs. Therefore, the objective of this study was to determine the optimal dietary SID Arg:Lys to maximize growth performance in 6- to 13-kg nursery pigs. In the current trial, average daily gain (ADG) and average daily feed intake (ADFI) responded quadratically to increasing SID Arg:Lys from 45% to 145%, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]) and ADG was maximized at 95.65% (95% CI [81.2%, 110.1%]). Together, the results of this study suggest the SID Arg:Lys requirement of 6- to 13-kg nursery pigs is at least 81%, based on the lower bounds of the 95% confidence intervals for maximum ADG and ADFI, but excess supplementation may reduce performance.

Citrulline and ADI-PEG20 reduce inflammation in a juvenile porcine model of acute endotoxemia.

Background: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of this study was to assess the efficacy of ADI-PEG20 with and without supplemental intravenous citrulline in mitigating hypovolemic shock, maintaining tissue levels of arginine, and reducing systemic inflammation in an endotoxemic pediatric pig model. Methods: Twenty 3-week-old crossbred piglets were implanted with jugular and carotid catheters as well as telemetry devices in the femoral artery to measure blood pressure, body temperature, heart rate, and respiration rate. The piglets were assigned to one of three treatments before undergoing a 5 h lipopolysaccharide (LPS) infusion protocol. Twenty-four hours before LPS infusion, control pigs (LPS; n=6) received saline, ADI-PEG20 pigs (n=7) received an injection of ADI-PEG20, and seven pigs (ADI-PEG20 + CIT pigs [n=7]) received ADI-PEG20 and 250 mg/kg citrulline intravenously. Pigs were monitored throughout LPS infusion and tissue was harvested at the end of the protocol. Results: Plasma arginine levels decreased and remained low in ADI-PEG20 + CIT and ADI-PEG20 pigs compared with LPS pigs but tissue arginine levels in the liver and kidney were similar across all treatments. Mean arterial pressure in all groups decreased from 90 mmHg to 60 mmHg within 1 h of LPS infusion but there were no significant differences between treatment groups. ADI-PEG20 and ADI-PEG20 + CIT pigs had less CD45+ infiltrate in the liver and lung and lower levels of pro-inflammatory cytokines in the plasma. Conclusion: ADI-PEG20 and citrulline supplementation failed to ameliorate the hypotension associated with acute endotoxic sepsis in pigs but reduced systemic and local inflammation in the lung and liver.

Diets containing phytobiotics, l-arginine, vitamin E and captopril modulate ascites syndrome-related genes expression in broiler chickens exposed to low ambient temperature.

BACKGROUND: Our hypothesis centred on the potential to mitigate ascites outbreaks in birds exposed to cold stress by inhibiting pulmonary artery contraction through dietary intervention. OBJECTIVE: This study aimed to evaluate the effect of natural and synthetic medications on growth performance, ascites-related parameters and the expression of ascites-related genes in the lung tissue of broiler chickens under low ambient temperature. METHODS: We randomly assigned 450 one-day-old male Ross 308 chicks to six dietary treatments across five replicate pens, each containing 15 chicks. The treatments included a basal diet (control), and the basal diet was supplemented with hydroalcoholic extracts of sumac (HES, 200 mg/kg), Syrian mesquite (HEM, 200 mg/kg), l-arginine (40% above requirement), captopril (15 mg/kg) and vitamin E (100 mg/kg). RESULTS: Diets containing HEM, l-arginine and vitamin E resulted in increased average daily gain on days 8-14 and 0-28, whereas HES showed a similar effect only during days 8-14 compared to the control diet (p < 0.05). Additionally, feed additives decreased packed cell volume, left and right ventricle volumes and systolic blood pressure (p < 0.05). Moreover, chickens fed the control and l-arginine diets exhibited higher levels of angiotensin converting enzyme (ACE) mRNA in lung tissue compared to those fed HES, HEM and captopril (p < 0.05). Meanwhile, supplementation with HEM and l-arginine increased the expression of inducible nitric oxide synthase (iNOS) mRNA in lung tissue compared to other treatments (p < 0.05). Regarding Cu/Zn-superoxide dismutase (Cu/Zn-SOD) expression, feed additives increased mRNA level in lung tissue, except for captopril (p < 0.05). CONCLUSIONS: This study demonstrates that the plant extracts may reduce the incidence of ascites syndrome not only through their antioxidant properties but also by modulating the expression of ACE, iNOS and Cu/Zn-SOD genes.

Effects of dietary arginine supplementation on muscle structure, meat characteristics and lipid oxidation products in lambs and its potential mechanisms of action.

This study aimed to assess the effect of dietary arginine supplementation on muscle structure and meat characteristics of lambs also considering lipid oxidation products and to contribute to reveal its mechanisms of action using tandem mass tagging (TMT) proteomics. Eighteen lambs were allocated to two dietary treatment groups: control diet or control diet with the addition of 1% L-arginine. The results revealed that dietary arginine supplementation increased muscle fibre diameter and cross-sectional area (P < 0.05), which was attributable to protein deposition, as evidenced by increased RNA content, RNA/DNA ratio, inhibition of apoptotic enzyme activity, and alterations in the IGF-1/Akt signaling pathway (P < 0.05). In addition, dietary arginine elevated pH24h, a* values, and IMF content, decreased shear force value and backfat thickness (P < 0.05), as well as decreased the formation of lipid oxidation products involved in meat flavor including hexanal, heptanal, octanal, nonanal and 1-octen-3-ol by increasing the antioxidant capacity of the muscle (P < 0.05). The proteomics results suggested that seven enrichment pathways may be potential mechanisms by which arginine affected the muscle structure and meat characteristics of lambs. In summary, arginine supplementation in lamb diets provides a safe and effective way to improve meat quality, and antioxidant capacity of muscle of lamb.

Usefulness of Perioperative Nutritional Therapy with the Glutamine/Arginine/Calcium ß-Hydroxy-ß-Methylbutyrate Product in Esophageal Cancer Surgery: A Single-Center Retrospective Study.

A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino-acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium ß-hydroxy-ß-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥ III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight were significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p < 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino-acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

Evaluating the impact of short-term nitrate-rich dietary supplementation on endothelial function in COPD: A randomized crossover study.

AIM: This study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration. METHODS: In this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series. RESULTS: Seventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m2, FEV1, 0.79 (0.67-1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels. CONCLUSIONS: Acute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect.

Comparative effectiveness of preemptive administration of ibuprofen and ibuprofen-arginine on the anesthetic success of inferior alveolar nerve block in teeth with symptomatic irreversible pulpitis - A double-blind randomized clinical trial.

OBJECTIVES: This study examined the impact of premedication with ibuprofen and ibuprofen-arginine and the influence of preoperative pain and anxiety on inferior alveolar nerve block (IANB) efficacy in cases of symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study involved 150 SIP patients who were randomly assigned to receive ibuprofen (600 mg), ibuprofen-arginine (1,155 mg), or a placebo 30 min before IANB. Preoperative anxiety and pain levels were assessed using the Modified Dental Anxiety Scale and the Heft-Parker visual scale. IANB efficacy was determined by the absence of or mild pain during the procedure. Statistical analysis included chi-square, z-tests, Analysis of Variance, and Student's t tests. RESULTS: The ibuprofen and ibuprofen-arginine groups exhibited significantly higher IANB success rates (62% and 78%, respectively) compared to the placebo group (34%). However, no significant difference was observed between the ibuprofen and ibuprofen-arginine groups. Patients with successful IANB in the ibuprofen and ibuprofen-arginine groups displayed lower median anxiety scores (8) than those with failed blocks (15) and lower mean preoperative pain scores (118.3). CONCLUSION: In cases of symptomatic irreversible pulpitis the preemptive medication with ibuprofen-arginine effectively increased the efficacy of the inferior alveolar nerve block The inferior alveolar nerve block efficacy was influenced by preoperative anxiety levels and the intensity of pain. CLINICAL RELEVANCE: This research underscores the potential benefits of oral premedication with ibuprofen and ibuprofen-arginine in improving anesthesia outcomes in cases of symptomatic irreversible pulpitis.

Preparation and Application of Decanoic Acid/Arginine Hydrogels to a Transdermal Formulation.

We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.

Impact of oral nutritional supplement composition on healing of different chronic wounds: A systematic review.

Chronic wounds are characterized by prolonged non-healing, significantly affecting patients' quality of life. Oral formulas may enhance the wound healing process and contribute to cost reduction in care. This review aimed to evaluate the effects of oral nutritional supplementation on chronic wound healing and provide insights into formula characteristics. A comprehensive search across Cinahl, Embase, PubMed, and Web of Science databases yielded nine studies from the past decade involving 741 patients ages 52 to 81.7 across various care settings: hospitals, long-term care facilities, and home care. Primary wound types included pressure injuries (58%), diabetic foot ulcers (40%), and venous ulcers (2%). The intervention duration ranged from 2 to 16 wk, with sample sizes varying from 24 to 270 patients. Notably, four studies reported a reduction in wound area and an increased healing rate with a hypercaloric, hyperproteic formula enriched with zinc and vitamins A, C, and E. However, two studies found no significant differences compared with control groups. Two other studies investigated a combination of arginine, glutamine, and ß-hydroxy-ß-methylbutyrate; however, they did not yield significant results, and one study favored a hyperproteic formula instead of a hyperproteic formula with arginine. This review provides evidence supporting the potential of oral nutritional supplementation to enhance the healing process of chronic wounds. Based on our findings, a desirable formula should be characterized by a high calorie and protein content and the inclusion of antioxidant micronutrients, including, but not limited to, vitamins A, E, C, and zinc.

Effect of 125% and 135% arginine on the growth performance, intestinal health, and immune responses of broilers during necrotic enteritis challenge.

The objective of this study was to evaluate the effects of 25% and 35% arginine supplementation in partially alleviating the effects of necrotic enteritis (NE) challenge on the production performance, intestinal integrity, and relative gene expression of tight junction proteins and inflammatory cytokines in broilers. Four hundred and eighty 1-day-old chicks were randomly allocated to the 4 treatments- Uninfected + Basal, NE + Basal, NE + Arg 125%, and NE + Arg 135%. NE was induced by inoculating 1 × 104Eimeria maxima sporulated oocysts on d 14 and 1 × 108 CFU/bird C. perfringens on d 19, 20, and 21 of age by oral gavage. The NE challenge significantly decreased body weight gain (BWG) (p < 0.05) and increased the feed conversion ratio (FCR) (p < 0.05). On d 21, the NE challenge also increased the jejunal lesion score (p < 0.05) and relative gene expression of IL-10 and decreased the expression of the tight junction proteins occludin (p < 0.05) and claudin-4 (p < 0.05). The 125% arginine diet significantly increased intestinal permeability (p < 0.05) and the relative gene expression of iNOS (p < 0.05) and IFN-γ (p < 0.05) on d 21 and the bile anti-C. perfringens IgA concentration by 39.74% (p < 0.05) on d 28. The 135% arginine diet significantly increased the feed intake during d 0 - 28 (p < 0.05) and 0 to 35 (p < 0.05) and increased the FCR on d 0 to 35 (p < 0.05). The 135% and 125% arginine diet increased the spleen CD8+: CD4+ T-cell ratio on d 28 (p < 0.05) and 35 (p < 0.05), respectively. The 135% arginine diet increased the CT CD8+:CD4+ T-cell ratio on d 35 (p < 0.05). In conclusion, the 125% and 135% arginine diets did not reverse the effect of the NE challenge on the growth performance. However, the 125% arginine diet significantly increased the cellular and humoral immune response to the challenge. Hence, the 125% arginine diet could be used with other feed additives to improve the immune response of the broilers during the NE challenge.

Phase-specific outcmes of arginine or branched-chain amino acids supplementation in low crude protein diets on performance, nutrient digestibility, and expression of tissue protein synthesis and degradation in broiler chickens infected with mixed Eimeria spp.

A 35-d study investigated the impact of dietary supplementation with Arginine (Arg) or branched-chain amino acids (BCAA) of broilers receiving low-protein diets whilst infected with mixed Eimeria species. All birds were given the same starter (d0-10) and finisher (d28-35) diets. The 4 grower diets used were a positive control (PC) with adequate protein (18.5%), a low protein diet (NC;16.5% CP), or the NC supplemented with Arg or BCAA. Supplemental AA was added at 50% above the recommended levels. The treatments were in a 4 × 2 factorial arrangement, with 4 diets, with or without Eimeria inoculation on d14. Birds and feed were weighed after inoculation in phases: prepatent (d14-17), acute (d18-21), recovery (d22-28), and compensatory (d29-35). Ileal digesta, jejunum, and breast tissue were collected on d21, 28, and 35. There was no diet × Eimeria inoculation on growth performance at any phase. Infected birds weighed less and consumed less feed (P < 0.05) in all phases. In the prepatent and acute phases, birds on the Arg diets had higher weight gain (P < 0.05) and lower FCR, similar to PC, when compared to NC and BCAA-fed ones. Infection reduced AA digestibility on d21 and 28 (Met and Cys). However, birds that received supplemental AA had higher digestibility (P < 0.05) of their respective supplemented AA on d 21 only. Infected birds had lower (P < 0.05) BO + AT and higher PEPT1 expression on d21. There was a diet × Eimeria interaction (P = 0.004) on gene expression at d28; 4EBP1 genes were significantly downwardly expressed (P < 0.05) in birds fed Arg diet, irrespective of infection. Infected birds exhibited an upward expression (P < 0.05) of Eef2 on d21 and d28 but experienced a downward expression on d35. Supplemental Arg and BCAA had variable effects on growth performance, apparent ileal AA digestibility, and genes of protein synthesis and degradation, but the effect of Arg on promoting weight gain, irrespective of the Eimeria challenge, was more consistent.

Effect of sex and milk replacer with or without supplemental carnitine and arginine on growth characteristics, carcass, and meat quality of artificially reared low-birth weight pigs.

This study compared milk replacer either remaining unsupplemented (CON) or supplemented with 0.5 g L-carnitine plus 16.7 g L-arginine/kg (CarArg) and fed to 48 low-birth weight (L-BtW) artificially reared piglets (24 per group) from days 7 to 28 of age. Eight farrowing series were needed to complete the study. On day 28, the lightest piglets were slaughtered, and the heaviest pigs were weaned. The heaviest pigs were weaned on day 28 and offered free access to a starter (weaning to 25 kg body weight [BW]), grower (25 to 60 kg BW), and finisher diet (60 to 96 kg BW on day 170 of age). After euthanization on days 28 and 170, blood was sampled for assessment of serum metabolite and hormone concentrations, and the semitendinosus muscle (STM) was weighed, and later subjected to enzyme activity analysis and assessment of myofiber characteristics. In the 170-d-old pigs carcass and meat quality traits were assessed. Growth data were analyzed accordingtoatwo-way analysis of variance (ANOVA), with dietary treatment and farrowing series as fixed effects, while remaining data were analyzed with dietary treatment, sex, their interaction, and farrowing series as main factors. Dietary treatments affected (P ≤ 0.049) muscle enzyme activity at both day 28, with greater citrate synthase (CS) and LDH activities and lower HAD:CS ratio in STM light portion, and lower LDH:CS ratio in STM dark portion, and 170 of age with lower HAD:CS ratio. In the starter period, CarArg pigs had greater average daily gain (P = 0.021) and average daily feed intake (P = 0.010). At slaughter, these pigs had lower (P = 0.013) glucose and greater (P = 0.022) urea serum concentrations. However, supplementing the milk replacer with carnitine and arginine had no long-term effects on growth performance, carcass composition, and meat quality of L-BtW pigs. In addition, muscle morphology and myofiber-related properties remained unaffected by the supplementation.

Breeding efforts to increase litter size in modern sows have inadvertently reduced the average birth weight of piglets, resulting in a higher number of piglets born with low-birth weight. These piglets are indeed vulnerable from birth and display relatively poor growth potential from a very early stage. For this reason, artificial rearing strategies are potentially a management option to improve the growth of these runt piglets. With an artificial rearing system, it is possible to provide specialized diets already during the suckling period, with inclusion of specific nutrients in certain concentrations suggested to improve the growth of runt piglets. Using an artificial rearing system allows for the provision of specialized diets during the suckling phase, which includes specific nutrients aimed at enhancing the growth of underdeveloped piglets. However, in the current experiment, the particular nutrients and their dosages did not significantly improve growth or other characteristics compared to the control group.

Effect of arginine supplementation on the growth performance, intestinal health, and immune responses of broilers during necrotic enteritis challenge.

The objective of this study was to evaluate the effect of 25% arginine supplementation as a functional amino acid in partially alleviating the detrimental effects of necrotic enteritis (NE) on the growth performance, serum biochemistry, gut integrity, and the relative gene expression of tight junction proteins and inflammatory cytokines in broilers during NE. Three hundred and sixty 1-day-old chicks were randomly allocated to 4 treatments in a 2 × 2 factorial arrangement -basal diet and 125% arginine diet, with or without NE challenge. NE was induced by inoculating 1 × 104Eimeria maxima sporulated oocysts on d 14 and 1 × 108 CFU/bird C. perfringens on d 19, 20, and 21. The NE challenge had a significant effect on the BWG (p < 0.05), FCR (p < 0.05), serum AST (p < 0.05), GLU (p < 0.05), and K+ (p < 0.05) levels, and intestinal permeability (p < 0.05) and jejunal lesion score (p < 0.05). A significant challenge × diet interaction effect was observed in the cecal tonsil CD8+: CD4+ T-cell ratio on d 21 (p < 0.05) and 28 (p < 0.05) and spleen CD8+: CD4+ T-cell ratio on d 21 (p < 0.05) and 35 (p < 0.05). Arginine supplementation significantly increased the CD8+: CD4+ T-cell ratio in uninfected birds but decreased the CD8+: CD4+ T-cell ratio in infected birds. On d 21, a significant interaction effect was observed on the relative expression of the iNOS gene (p < 0.05). Arginine supplementation significantly downregulated the expression of the iNOS gene in infected birds. A significant effect of the challenge (p < 0.05) was observed on the relative gene expression of the ZO-1 gene in the jejunum. NE challenge significantly downregulated the expression of the ZO-1 gene on d 21. In conclusion, arginine supplementation did not alleviate the depression in growth performance and disease severity during the NE challenge. However, arginine downregulated the expression of inflammatory cytokines and enzymes, preventing inflammatory injury to the tissues during NE. Hence, arginine might be supplemented with other alternatives to downregulate inflammatory response during NE in poultry.

Impact of the arginine silicate inositol complex on bone metabolism in broiler chickens with tibial dyschondroplasia caused by manganese deficiency.

1. Tibial dyschondroplasia (TD) is a skeletal disorder in broilers that has financial implications, necessitating dietary modifications to reduce the prevalence of this disease. This study explored how arginine silicate inositol complex (ASI) supplementation affected tibial growth plate (TGP) and overall bone health in broilers with manganese (Mn) deficiency-induced TD.2. A total of 240 broiler chicks were divided into four groups, each consisting of 60 birds (15 replicates of four broilers each) as follows: i) Control, with 60 mg Mn per kg of diet; ii) ASI, with 60 mg Mn and 1 g ASI per kg of diet; iii) TD, with 22 mg Mn per kg of diet, and iv) TD+ASI, with 22 mg Mn and 1 g ASI per kg of diet.3. It was found that ASI supplementation increased tibial bone length in Mn-deficient TD broilers (p = 0.007). There was no Mn x ASI interaction for other bone morphometry variables (p > 0.05). However, both tibial bone mineral content and density were affected by Mn and ASI (p < 0.05). With ASI supplementation, serum bone-specific alkaline phosphatase and osteocalcin levels were elevated in the TD+ASI group compared to the TD group (p < 0.001). In the TD group, osteoprotegerin (OPG) levels in the TGP decreased compared to the control groups (p < 0.001).4. In contrast, ASI supplementation in the TD broilers counteracted the decrease in OPG compared to TD broilers without ASI supplementation (p < 0.001). The Mn level and ASI supplementation significantly influenced the OPG/receptor activator of the nuclear factor-κB ligand ratio (p < 0.001).5. In conclusion, the results demonstrated that inclusion of ASI in broiler diets could enhance bone formation variables by controlling OPG levels in the TGP, potentially serving as an effective method to decrease the occurrence of TD.

Dietary arginine regulates the growth performance, antioxidant capacity, and immune response in Culter alburnus.

Culter alburnus is sensitive to stressors. Arginine is a precursor of nitric oxide, which can effectively relieve the level of oxidative stress and improve the antioxidant and immune capacity of fish. The effect of different arginine levels on topmouth culter (Culter alburnus) fry development performance, liver antioxidant capacity, and immune parameters were investigated in this study. Five diets (1.96%, ARG1, control group; 2.28%, ARG2; 2.52%, ARG3; 2.81%, ARG4; 3.09%, ARG5) were used to feed fry (initial weight 0.31 ± 0.01 g) for 8 weeks. The data showed that the final weight (FW), weight gain rate (WGR), and specific growth rate (SGR) of the ARG3 and ARG4 groups were significantly improved, while the feed conversion ratio (FCR) reduced significantly. Compared with the ARG1 group, all groups remarkably reduced the crude ash content of the whole body. The activity of hepatic superoxide dismutase (SOD) and the content of hepatic glutathione (GSH) were significantly increased in the ARG3 and ARG4 groups, while the malondialdehyde (MDA) content was significantly decreased. Compared with the ARG1 group, arginine levels in ARG2, ARG3, and ARG4 groups up-regulated the expression levels of Nrf2, down-regulated the gene expression level of Keap1 in the liver. And the expression of Nrf2/Keap1 pathway downstream genes Mn-SOD and CAT was up-regulated in ARG2 and ARG3 groups. Furthermore, the expression levels of MyD88 and IL-1ß were down-regulated, and the anti-inflammatory gene TGF-ß expression levels were up-regulated in the ARG2, ARG3, and ARG4 groups. Additionally, compared to the ARG1 group, there was a significant increase in the relative expression levels of the C3 and C4 genes in the ARG4 group. In conclusion, 2.28-2.81% dietary arginine levels improved the growth performance, promoted antioxidant capacity, and enhance immune response. The optimal level of arginine was determined by the quadratic regression analysis of SGR and FCR to be 2.55% of diet (5.43% of dietary protein) and 2.53% of diet (5.38% of dietary protein), accordingly.