Amino Acid Infusion Research Articles

Comparative evaluation of forced air warming and infusion of amino acid-enriched solution on intraoperative hypothermia in patients undergoing head and neck cancer surgeries: A prospective randomised study.

Background:Inadvertent core hypothermia is a common occurrence during general anaesthesia. Forced air warming (FAW) is the most effective perianaesthetic warming system, but it may lead to thermal discomfort. Amino acids (AAs) have been used to prevent hypothermia, but no study has compared the effect of AA infusion with FAW systems. We have conducted this study to compare the effects of external heating (FAW system) and internal heat generation (AA infusion) in preventing hypothermia during anaesthesia.Methods:After institutional review board approval, 80 American Society of Anesthesiologists Grade I/II adult patients admitted for head and neck cancer surgeries lasting more than 2 h under general anaesthesia were included. The patients were randomly divided into two groups using computer-generated codes to receive AA infusion at 3 mL/kg/h, Group AA (N = 40), or normal saline at 3 mL/kg/h with FAW, Group FA (N = 40) till the end of surgery. Standard anaesthetic technique and monitoring was used in all the patients.Results:The baseline mean temperature in both the groups was comparable. The core temperature was similar in the two groups at 30 min (35.6 ± 0.54 vs 35.5 ± 0.54), 60 min (35.5 ± 0.63 vs 35.3 ± 0.60), 90 min (35.5 ± 0.79 vs 35.2 ± 0.66), 120 min (35.6 ± 0.93 vs 35.2 ± 0.78), 150 min (35.7 ± 0.88 vs 35.3 ± 0.89) and 180 min (35.8 ± 1.01 vs 35.3 ± 0.95) in Groups FA and AA, respectively (P > 0.05). However, the core temperature was significantly higher in Group FA at 210 min (35.8 ± 1.0 vs 35.3 ± 0.85; P = 0.01), 240 min (35.9 ± 1.0 vs 35.4 ± 0.90; (P = 0.001), 270 min (35.9 ± 1.12 vs 35.6 ± 0.97; P = 0.002) and 300 min (36.0 ± 1.12 vs 35.6 ± 1.02; P = 0.002), respectively. Clinically relevant hypothermia (at least one measurement <35.5°C) was comparable between the two groups.Conclusion:The AA infusion can be used as an alternative to FAW in preventing intraoperative hypothermia under general anaesthesia especially in places where FAW system is unavailable.

Effect of cyclooxygenase-2 inhibitors at therapeutic doses on body temperature during anesthesia in healthy dogs administered with amino acids

In healthy dogs, amino acid infusion significantly attenuates the decrease in body temperature during anesthesia by facilitating insulin secretion, suggesting that such an increase in insulin secretion is related to increased heat production. In dogs, selective cyclooxygenase-2 (COX-2) inhibitors, which are used for pain relief in veterinary medicine, possess anti-pyretic action. And, in mice and humans, selective COX-2 inhibitors increase insulin secretion and sensitivity. Therefore, treatment with COX-2 inhibitors may negate or accelerate the attenuating effect on decreased body temperature during anesthesia by amino acid infusion. In the present study, influences on insulin secretion and body temperature by treatment with meloxicam or robenacoxib at therapeutic dose were evaluated in healthy dogs. Treatment with meloxicam or robenacoxib did not affect insulin secretion in the unanesthetized and anesthetized dogs, and did not affect body temperature and heart rate under the anesthetized condition with amino acid infusion. In conclusion, COX-2 inhibitors at therapeutic doses did not affect body temperature during anesthesia in dogs administered amino acids.

Broadening Horizons with 225Ac-DOTATATE Targeted Alpha Therapy for Gastroenteropancreatic-Neuroendocrine Tumor Patients Stable or Refractory to 177Lu-DOTATATE PRRT: First Clinical Experience on the Efficacy and Safety

Background: The curative option for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is surgery, but as the majority of the patients are diagnosed at the late stage with metastasis and require systemic treatment. Currently available systemic therapies are inadequate and produce only symptomatic relief or at the best stable disease. Therefore, there is an increasing need for novel therapeutic options in the treatment of metastatic GEP-NETs. Although beta-emitting peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is one of the FDA approved standard treatment options, alpha therapy on the radiobiological basis is considered superior to beta-emitting 177Lutetium (177Lu) based PRRT. This is due to the double-stranded DNA breaks by alpha particles causing high cytotoxic activity on the cellular level with minimal bystander effects. However, clinical evidence in this context is sparse, hence, the objective of this study was to investigate and present the early results on the efficacy, safety, and quality of life of 225Ac-DOTATATE targeted alpha therapy (TAT) in patients with advanced, progressive, 177Lu-DOTATATE refractory, and somatostatin receptor (SSTR) expressing metastatic GEP-NETs. Methods: In this prospective study, we recruited patients with metastatic GEP-NETs who were stable or progressive disease on 177Lu-DOTATATE therapy. We offered 225Ac-DOTATATE therapy as an experimental treatment option after obtaining institutional review board approval. All patients underwent 68Ga-DOTANOC PET/CT scan to ensure high SSTR expression even after repeated 177Lu-DOTATATE therapy cycles. Systemic TAT was performed in all the patients with 225Ac-DOTATATE (100 KBq/Kg body weight) at an interval of 8 weeks. The primary end-point was to assess the objective response (measured by RECIST 1.1 and functional M. D. Anderson criteria). The secondary end-points included biochemical response assessment as per the Italian Trials in Medical Oncology (ITMO), adverse-event profile as per CTCAE v5.0, and clinical response assessment by the quality of life (assessed with EORTC QLQ-GI.NET21 patient-based questionnaire). The renal, hepatic, and haematological evaluation were performed before and after every cycle of 225Ac-DOTATATE TAT at 2, 4 and 8-week intervals. Findings: Between April 2018 and February 2019, 21 patients (9 females, 12 males, median age 54 years, IQR: 50 - 60 years) with either stable disease after completing 177Lu-DOTATATE therapy (12, 57%) or progressive disease on 177Lu-DOTATATE therapy (9, 43%) were included in the study. The mean administered cumulative 225Ac-DOTATATE therapy was 20794 ± 6660 KBq over a median of 3 cycles. The morphological response was assessed in 20/21 patients that revealed partial remission in 10 and stable disease in 10. There were no documented disease progression or deaths in the median follow-up of 9 months (range: 2 - 12 months). There was a significant decrease in the plasma chromogranin level post-225Ac-DOTATATE therapy (P=0·0019). While a significant decrease in the endocrine (P=0·0011) and gastrointestinal symptoms (P=0·0002) were noted, there was a significant improvement in the functional scale: disease-related worries (P<0·0001). The most common adverse effects (AEs) were loss of appetite, nausea, and vomiting, however, were limited to grade 1 or 2 toxicities. Majority of the patients experienced these AEs at the time of amino acid infusion which was co-administered with 225Ac-DOTATATE therapy and was resolved after a few hours of amino acid infusion. Interpretation: Our short-term clinical results indicate 225Ac-DOTATATE TAT as a promising treatment option which adds a new dimension in patients who are refractory to 177Lu-DOTATATE therapy, or have reached the maximum prescribed cycles of 177Lu-DOTATATE therapy. However, Longterm clinical data are in the process of collection for the assessment of sustained tumor response with 225Ac-DOTATATE TAT. Funding Statement: The authors state: None. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: Ethical clearance received Ref. No IEC-517

Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial

ObjectiveTo determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery. MethodsAdult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed. ResultsSixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P = .84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P < .0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P = .033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P = .046). ConclusionsCommencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials.

The effect of early versus late lipid infusion in parenteral nutrition on the biochemical and cortical auditory evoked potential parameters in preterm neonates

BackgroundAs brain activity depends greatly on the functions provided by lipid membranes, dietary fat in early life can affect the developing nervous system. Despite the adoption of an early more aggressive parenteral nutrition approach with amino acid infusions still reluctance to the early use of intravenous lipids in neonates. AimTo compare the effect of delayed versus early introduction of intravenous lipid in preterm on the biochemical parameters and on brain development by the cortical auditory evoked potential (CAEP) latency and amplitude. MethodsThis is a comparative study included 49 neonates admitted at the ain shams university NICUs. Participants were divided into two groups: 26 in group of early lipid infusion and 23 in late lipid infusion, Demographic data, and biochemical parameters were documented during the 1st 2 weeks of life. The CAEP was performed at age of 6 months. The latency and amplitude of P1 were recorded and compared between both groups. ResultsIn the present work we found that group of early lipid infusion had reach their full oral intake earlier with shorter duration of parenteral nutrition and length of stay. They had better weight gain and significantly better glucose level control than group of late lipid infusion. There was no significant difference in the other chemical parameters between both groups expect for the higher incidence of cholestasis in the group of late lipid infusion. At 6 months of age, the group of early lipid infusion had significantly shorter latency and amplitude of P1 than the group of late lipid infusion. Conclusionearly effective nutrition positively affect feeding tolerance and weight gain and maturation of higher brain centers brain.

Magnetic Field Extraction Techniques in Preparing High-Quality Tea Infusions

Tea is one of the most popular drinks in the world, commonly consumed by consumers from all age groups mainly due to its refreshing taste, attractive aroma, and potentially beneficial impact on health. The composition of a tea drink depends on numerous factors, such as time and brewing temperature, degree of crumbling of tea leaves, and degree of mixing. Diffusion of the polyphenolic compounds, minerals, caffeine or theanine typical of tea infusions have been the subject of studies conducted by numerous authors. Promoting the extraction of amino acids from tea leaves when preparing infusions through the induction of a magnetic field constitutes not only another step towards the optimisation of the extraction process, but is also one of the methods to improve the nutritional value of tea infusions. The purpose of this work was to verify a hypothesis concerning the improvement of the extraction of amino acids from dried tea during the preparation of infusions by applying a permanent or variable magnetic field induced under laboratory conditions. A variable magnetic field applied as a factor assisting extraction resulted in an increased concentration in the total number of amino acids in green and black tea infusions. A statistically significant improvement in the level of free amino acids was observed after application of extraction assisted by a variable magnetic field with induction at 100 mT and a frequency of 50 Hz. Extraction using a variable magnetic field for tea infusions may constitute a good solution to assist traditional water extraction methods for research purposes.

Prolonged amino acid infusion into intrauterine growth-restricted fetal sheep increases leucine oxidation rates.

Overcoming impaired growth in an intrauterine growth-restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We subjected fetal sheep to chronic placental insufficiency and tested whether prolonged amino acid infusion would increase protein accretion in these IUGR fetuses. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg-1·day-1 (IUGR-AA) or saline (IUGR-Sal) during late gestation. At the end of the infusion, fetal plasma leucine, isoleucine, lysine, methionine, and arginine concentrations were higher in the IUGR-AA than IUGR-Sal group ( P < 0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and norepinephrine concentrations were similar between IUGR groups, but glucagon concentrations were fourfold higher in the IUGR-AA group ( P < 0.05). Net umbilical amino acid uptake rate did not differ between IUGR groups; thus the total amino acid delivery rate (net umbilical amino acid uptake + infusion rate) was higher in the IUGR-AA than IUGR-Sal group (30 ± 4 vs. 19 ± 1 μmol·kg-1·min-1, P < 0.05). Net umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR groups. Fetal leucine oxidation rate, measured using a leucine tracer, was higher in the IUGR-AA than IUGR-Sal group (2.5 ± 0.3 vs. 1.7 ± 0.3 μmol·kg-1·min-1, P < 0.05). Fetal protein accretion rate was not statistically different between the IUGR groups (1.6 ± 0.4 and 0.8 ± 0.3 μmol·kg-1·min-1 in IUGR-AA and IUGR-Sal, respectively) due to variability in response to amino acids. Prolonged amino acid infusion into IUGR fetal sheep increased leucine oxidation rates with variable anabolic response.

Sugammadex and amino acid infusion can contribute to safe anesthetic management of variegate porphyria

BackgroundVariegate porphyria (VP) is an inherited type of porphyria characterized by cutaneous manifestations and/or acute neurovisceral attacks. We report successful anesthetic management of VP.Case presentationA 66-year-old woman with VP was scheduled to undergo distal pancreatectomy for pancreatic cancer. Medical history was unremarkable except for sudden onset of abdominal pain that occurred every few months, possibly due to VP. There was no abnormality in laboratory data except for a mild increase in creatinine levels. General anesthesia was induced and maintained with total intravenous anesthesia using propofol, remifentanil, and rocuronium. Blood glucose levels were measured every hour and glucose administered to prevent hypoglycemia. Amino acids were also infused to treat hypothermia. Upon completion of distal pancreatectomy, sugammadex was administered to reverse neuromuscular blockade. She was neurologically intact and discharged on postoperative day 15 with no acute attack.ConclusionsSugammadex and amino acids can be used safely in patients with VP.

Effect of an intraoperative infusion of amino acids on body temperature, serum biochemistry, serum insulin and recovery variables in healthy dogs undergoing ovariohysterectomy

Change in body temperature (BT), serum biochemistry and recovery variables were compared after infusion of amino acids (AA) or lactated Ringer’s solution (LRS) in dogs undergoing ovariohysterectomy. Dogs received eight...

Haemodynamic or metabolic stimulation tests to reveal the renal functional response: requiem or revival?

ABSTRACTRenal stimulation tests document the dynamic response of the glomerular filtration rate (GFR) after a single or a combination of stimuli, such as an intravenous infusion of dopamine or amino acids or an oral protein meal. The increment of the GFR above the unstimulated state has formerly been called the renal functional reserve (RFR). Although the concept of a renal reserve capacity has not withstood scientific scrutiny, the literature documenting renal stimulation merits renewed interest. An absent or a blunted response of the GFR after a stimulus indicates lost or diseased nephrons. This information is valuable in preventing, diagnosing and prognosticating acute kidney injury and pregnancy-related renal events as well as chronic kidney disease. However, before renal function testing is universally practiced, some shortcomings must be addressed. First, a common nomenclature should be decided upon. The expression of RFR should be replaced by renal functional response. Second, a simple protocol must be developed and propagated. Third, we suggest designing prospective studies linking a defective stimulatory response to emergence of renal injury biomarkers, to histological or morphological renal abnormalities and to adverse renal outcomes in different renal syndromes.

Symposium review: Amino acid uptake by the mammary glands: Where does the control lie?

Milk protein yield responses to changes in the profile of essential amino acids absorbed by the gastrointestinal tract or circulating in blood plasma do not follow the classic limiting amino acid response, in part because of an ability of the mammary glands to modify their blood flow rate and net clearance of amino acids out of plasma. The hypothesis that mammary blood flow is locally regulated to maintain ATP balance accounts for observed changes in flow due to postruminal glucose, insulin, and essential amino acid (EAA) infusions. An additional hypothesis that net mammary uptakes of metabolites from blood are affected by perturbations in their respective arterial concentrations and the rate of mammary blood flow also appears to hold for the energy metabolites glucose, acetate, β-hydroxybutyrate, and fatty acids. However, net EAA uptakes by the mammary glands are poorly predicted by models considering arterial concentrations and blood flow rates only. Evidence points to intramammary protein synthesis and secretion as the determinant of net EAA uptake. The intracellular signaling network anchored by the mechanistic target of rapamycin complex 1 stands as an excellent candidate to explain nutritional effects on milk protein synthesis because it integrates information on physiological and nutritional state to affect protein synthesis and cell metabolism, growth, proliferation, and differentiation in many cell types. In mammary cells in vitro and in vivo, the mechanistic target of rapamycin complex 1, integrated stress response, and glycogen synthase kinase-3 networks that contribute to regulation of initiation of mRNA translation are responsive to acute changes in nutrient supply and EAA profile. However, after several days of postruminal infusion of balanced and imbalanced EAA profiles, these signaling networks do not appear to continue to account for changes in milk protein yields. Gene expression evidence suggests that regulation of components of the unfolded protein response that control biogenesis of the endoplasmic reticulum and differentiation of a secretory phenotype may contribute to effects of nutrition on milk protein yield. Connections between early signaling events and their long-term consequences should be sought.

Hyperkalemia in patients treated with endoradiotherapy combined with amino acid infusion is associated with severe metabolic acidosis

BackgroundAmino acid co-infusion for renal protection in endoradiotherapy (ERT) applied as prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) or peptide receptor radionuclide therapy (PRRT) has been shown to cause severe hyperkalemia. The pathophysiology behind the rapid development of hyperkalemia is not well understood. We hypothesized that the hyperkalemia should be associated with metabolic acidosis.ResultsTwenty-two patients underwent ERT. Prior to the first cycle, excretory kidney function was assessed by mercapto-acetyltriglycine (MAG-3) renal scintigraphy, serum biochemistry, and calculated glomerular filtration rate (eGFR). All patients received co-infusion of the cationic amino acids L-arginine and L-lysine for nephroprotection. Clinical symptoms, electrolytes, and acid-base status were evaluated at baseline and after 4 h.No patient developed any clinically relevant side effects. At baseline, acid base status and electrolytes were normal in all patients. Excretory kidney function was normal or only mildly impaired in all except two patients with stage 3 renal insufficiency. All patients developed hyperkalemia. Base excess and HCO3− were significantly lower after 4 h. In parallel, mean pH dropped from 7.36 to 7.29. There was a weak association between calculated (r = − 0.21) as well as MAG-3-derived GFR (r = − 0.32) and the rise in potassium after 4 h.ConclusionAmino acid co-infusion during ERT leads to severe metabolic acidosis which induces hyperkalemia by potassium hydrogen exchange. This novel finding implies that commercially available bicarbonate solutions might be an easy therapeutic option to correct metabolic acidosis rapidly.

The role of renal response to amino acid infusion and oral protein load in normal kidneys and kidney with acute and chronic disease.

High protein intake and hyperfiltration have been a focus of major interest as potential mechanism(s) of progression of renal disease. This review will examine: the renal response to a protein meal or amino acid infusion and its use to test the renal functional reserve (RFR); new methods to evaluate RFR; the use of RFR in various pathophysiologic conditions. The renal response to protein/amino acid infusion involves several mechanisms, including nitric oxide, insulin, glucagon, arginine vasopressin, urea, the renal N-Methyl-D-Aspartate Glutamate receptor and modulation of the activity of the tubuloglomerular feedback system. Dose-response studies to evaluate RFR suggest the presence of a potential ceiling. The utilization of a noninvasive technique such as Doppler ultrasonography is trying to simplify the measurement of RFR and to bring this test into different clinical settings. There is increased interest in the presence or absence of RFR in patients with acute kidney injury, hypertension, chronic kidney disease, and its potential long-term implication regarding renal function. The renal response to protein may help us understand the relationship between hyperfiltration, progression of renal disease, and other conditions (overall mortality, cardiovascular complications, and so on) currently being explored.

Disuse skeletal muscle atrophy in humans. Proteomic and molecular adaptations

Disuse skeletal muscle atrophy in humans. Proteomic and molecular adaptations

Coupling Microchip Electrospray Ionization Devices with High Pressure Mass Spectrometry.

A microchip electrospray ionization source was coupled with high pressure mass spectrometry (HPMS). A continuous atmospheric inlet consisting of a stainless steel capillary and DC ion optics was designed to conduct ions into the mass spectrometer. Infusions of amino acids and peptides were performed and detected with a miniature cylindrical ion trap (mini-CIT)-based mass spectrometer operated at ≥1 Torr with air as the buffer gas. Detection of glycine and thymopentin (separately) demonstrated the mass range of the mini-CIT detector could span from m/z 75 to 681. A microchip capillary electrophoresis (CE) separation with mini-CIT detection was performed, and the results were compared with detection using a commercial instrument (Waters Synapt G2). Comparable separation efficiencies were observed with both mass spectrometers as detectors, with about 6 times better signal-to-noise observed on the Synapt G2. Comparison of mass spectra in the two systems reveals similar features observed, but with wider peak widths in the mini-CIT than on the Synapt G2 as expected due to high-pressure operation.

A supplemental intravenous amino acid infusion sustains a positive protein balance for 24\xa0hours in critically ill patients

BackgroundProviding supplemental amino acids to ICU patients during a 3-h period results in improved whole-body net protein balance, without an increase in amino acid oxidation. The primary objective was to investigate if a 24-h intravenous amino acid infusion in critically ill patients has a sustained effect on whole-body protein balance as was seen after 3 h. Secondary objectives were monitoring of amino acid oxidation rate, urea and free amino acid plasma concentrations.MethodsAn infusion of [1-13C]-phenylalanine was added to ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed intravenous infusions of [ring-2H5]-phenylalanine and [3,3-2H2]-tyrosine were used to assess whole-body protein synthesis and breakdown, to calculate net protein balance and to assess amino acid oxidation at baseline and at 3 and 24 hours. An intravenous amino acid infusion was added to nutrition at a rate of 1 g/kg/day and continued for 24 h.ResultsEight patients were studied. The amino acid infusion resulted in improved net protein balance over time, from -1.6 ± 7.9 μmol phe/kg/h at 0 h to 6.0 ± 8.8 at 3 h and 7.5 ± 5.1 at 24 h (p = 0.0016). The sum of free amino acids in plasma increased from 3.1 ± 0.6 mmol/L at 0 h to 3.2 ± 0.3 at 3 h and 3.6 ± 0.5 at 24 h (p = 0.038). Amino acid oxidation and plasma urea were not altered significantly.ConclusionWe demonstrated that the improvement in whole-body net protein balance from a supplemental intravenous amino acid infusion seen after 3 h was sustained after 24 h in critically ill patients.Trial registrationThis trial was prospectively registered at Australian New Zealand Clinical Trials Registry. ACTRN, 12615001314516. Registered on 1 December 2015.

Role of Glucagon in Catabolism and Muscle Wasting of Critical Illness and Modulation by Nutrition.

Critical illness is hallmarked by muscle wasting and disturbances in glucose, lipid, and amino acid homeostasis. Circulating concentrations of glucagon, a catabolic hormone that affects these metabolic pathways, are elevated during critical illness. Insight in the nutritional regulation of glucagon and its metabolic role during critical illness is lacking. To evaluate whether macronutrient infusion can suppress plasma glucagon during critical illness and study the role of illness-induced glucagon abundance in the disturbed glucose, lipid, and amino acid homeostasis and in muscle wasting during critical illness. In human and mouse studies, we infused macronutrients and manipulated glucagon availability up and down to investigate its acute and chronic metabolic role during critical illness. In critically ill patients, infusing glucose with insulin did not lower glucagon, whereas parenteral nutrition containing amino acids increased glucagon. In critically ill mice, infusion of amino acids increased glucagon and up-regulated markers of hepatic amino acid catabolism without affecting muscle wasting. Immunoneutralizing glucagon in critically ill mice only transiently affected glucose and lipid metabolism, did not affect muscle wasting, but drastically suppressed markers of hepatic amino acid catabolism and reversed the illness-induced hypoaminoacidemia. These data suggest that elevated glucagon availability during critical illness increases hepatic amino acid catabolism, explaining the illness-induced hypoaminoacidemia, without affecting muscle wasting and without a sustained impact on blood glucose. Furthermore, amino acid infusion likely results in a further breakdown of amino acids in the liver, mediated by increased glucagon, without preventing muscle wasting. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals. To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults. Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions. Eligible participants were healthy lean (body mass index, <25 kg/m2; age, 37 ± 3 years; n = 10) and obese (body mass index >30 kg/m2; age 35 ± 3 years; n = 11) subjects. Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions. Mitochondrial respiration and ATP production. AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P < 0.05), but not obese, subjects. Furthermore, AA infusion increased the uncoupled (i.e., non-ADP-stimulated) respiration of SS mitochondria in the lean subjects only (P < 0.05). AA infusion had no effect on any of these parameters in IMF mitochondria in either lean or obese subjects (P > 0.05). Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals.

Two mutations in the HR2 region of Newcastle disease virus fusion protein with a cleavage motif \u201cRRQRRL\u201d are critical for fusogenic activity

BackgroundNewcastle disease virus (NDV) causes severe diseases in avian species. Its fusion protein cleavage site (Fcs) is a major contributor to virulence and membrane fusion. Previous studies showed that a change from phenylalanine (F) to lysine (L) at position 117 of the virulent strain fusion protein, which has the polybasic amino acid Fcs motif “112RRQKR↓F117”, blocked syncytium formation. However, we observed that F proteins of the virulent strain F48E9 and avirulent strain LaSota substituted with an identical cleavage motif, “112RRQRR↓L117”, induced extensive and slight syncytium formation, respectively. Accordingly, we hypothesized that the difference in syncytium formation is caused by other regions of the fusion protein.ResultsThe exchanged regions between the fusion proteins of two strains, F48E9 and LaSota, showed that the region from amino acid 118–499 plays an important role in modulation of fusogenic activity in transfected cells. Further dissection of this region indicated that replacement of two amino acids (N479D, R486S) in heptad repeat 2 (HR2) of the avirulent fusion protein by the virulent counterpart resulted in fusion promotion. Moreover, the role of these two amino acids in fusion is dependent on the unique Fcs sequence “RRQRR↓L”.ConclusionsOur results demonstrated that two amino acids (D479, S486) of the virulent strain F protein with this unique Fcs were critical for promoting fusogenic activity, and residue F or L at position 117 did not affect syncytium formation. These findings provide novel insights into fusogenic triggering by the fusion protein and may be useful for designing antiviral peptides.

Short communication: Short-term intravenous amino acid infusions as a method to detect limiting amino acids in dairy cattle diets

We hypothesized that the addition of limiting AA increases dry matter intake (DMI) by reducing anaplerosis and hepatic oxidation. Accordingly, the objective of this work was to examine the effects of short-term intravenous infusions of Met, Lys, and His (which are considered the most limiting AA) on DMI as a method to detect whether specific AA are limiting in dairy cow diets. We conducted 4 experiments using Holstein cows in the immediate postpartum period to address this objective. The first experiment used 4 cows 6 to 10 d postpartum (PP) in a 4 × 4 Latin square design with 1-d periods including 12 h for infusions and 12 h for recovery. Treatments were continuous infusions of 5 (low), 10 (medium), or 15% (high) of the calculated requirement of metabolizable Met, Lys, and His or 0.9% saline (control, CONT). In the second and third experiments, 8 cows (4-12 d PP) were divided into 2 groups of 4 cows, and each group received a different diet formulated to either be low in Lys (experiment 2) or Met (experiment 3). Each experiment was a crossover design with two 1-d periods with 12-h infusions (continuous) and 12 h for recovery. Treatments were 15% of the calculated requirement of metabolizable Met, Lys, and His (high), or 0.9% saline (CONT). In the fourth experiment, 5 cows (4-14 d PP) were used in a 5 × 5 Latin square design. Periods were 2 d in which treatments were continuously infused for the first 46 h. Treatments were 0.9% saline (CONT), all (Lys, Met, and His), LM (Lys and Met), LH (Lys and His), and MH (Met and His); dosages were equal to the estimated shortage in each specific AA. In each experiment, feed intake was recorded by a computerized data acquisition system, milk yield was recorded, and milk composition was analyzed for fat, protein, lactose, and milk urea nitrogen (MUN) concentrations. Treatments did not affect DMI or yield of milk or milk components in the first experiment. In the second experiment, AA treatment increased protein percentage and reduced lactose percentage but had no effect on protein and lactose yields or DMI. In the third experiment, the AA treatment tended to increase yields of milk, lactose, and protein as well as MUN concentration but did not affect DMI. In the fourth experiment, no effects were detected for DMI and milk yield, whereas the all, LH, and LM treatments reduced milk lactose concentration compared with CONT, and MH increased MUN concentration compared with CONT and other treatments. These results failed to provide support for our hypothesis that short-term addition of these potentially limiting AA will increase DMI. This may be due to our hypothesis being inaccurate or to other factors; other limiting AA could have prevented the effects of Lys, Met, and His infusions or the infusion periods could have been too short to induce a response in DMI. Accordingly, short-term infusion of AA is probably not a sensitive method to detect limiting AA in dairy cow diets.