Antioxidant Activity Derived from Marine Green-Lipped Mussel Perna canaliculus Extracts in Mice.

This study investigates the antioxidant activities of lipid, protein, and carbohydrate extracts from the marine mollusk Perna canaliculus. Lipids were extracted using acetone, which was followed by protein extraction using the broad-spectrum enzyme Alcalase and then carbohydrate extraction using cetylpyridinium chloride. Eighty white BALB/c mice were divided into eight groups according to the administered extracts. Groups 1 and 5 were the control and toxin control groups, respectively. Groups 2, 3, and 4 were administered lipid, protein, and carbohydrate extracts, respectively. The other groups were administered P. canaliculus extracts as well as gentamicin and acetaminophen, known as ethanolic extracts, derived from Nerium oleander to induce oxidation stress. All groups showed significant improvements in body weight (p < 0.05). The lipid extract group showed a significant decrease in low-density lipoprotein cholesterol (p < 0.05) and a significant increase in high-density lipoprotein cholesterol (p < 0.05). After the toxin injection, all groups treated with P. canaliculus extracts showed increased antioxidant effects on hepatocytes (p < 0.05). The lipid extracts induced antioxidant effects to protect the kidney by increasing lipid peroxidation (p < 0.05) and catalase activities (p < 0.05). Also, protein extracts showed antioxidant effects by increasing glutathione and catalase levels significantly (p < 0.005). In conclusion, P. canaliculus extracts, especially lipids and proteins, have potent antioxidant activities that protect vital organs from oxidation stress.

Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis.

The traditional treatment for phenylketonuria (PKU) is a phenylalanine (Phe)-restricted diet, supplemented with a Phe-free/low-Phe protein substitute. Pharmaceutical treatment with synthetic tetrahydrobiopterin (BH4), an enzyme cofactor, allows a patient subgroup to relax their diet. However, dietary protocols guiding the adjustments of protein equivalent intake from protein substitute with BH4 treatment are lacking. We systematically reviewed protein substitute usage with long-term BH4 therapy. Electronic databases were searched for articles published between January 2000 and March 2020. Eighteen studies (306 PKU patients) were eligible. Meta-analyses demonstrated a significant increase in Phe and natural protein intakes and a significant decrease in protein equivalent intake from protein substitute with cofactor therapy. Protein substitute could be discontinued in 51% of responsive patients, but was still required in 49%, despite improvement in Phe tolerance. Normal growth was maintained, but micronutrient deficiency was observed with BH4 treatment. A systematic protocol to increase natural protein intake while reducing protein substitute dose should be followed to ensure protein and micronutrient requirements are met and sustained. We propose recommendations to guide healthcare professionals when adjusting dietary prescriptions of PKU patients on BH4. Studies investigating new therapeutic options in PKU should systematically collect data on protein substitute and natural protein intakes, as well as other nutritional factors.

Powder suspensions in non-aqueous vehicles for delivery of therapeutic proteins.

Formulating biopharmaceuticals is a challenging task due to their complex and sensitive nature. Protein drugs are typically marketed either as an aqueous solution or as a lyophilizate. Usually aqueous solutions are preferred as neither drying nor reconstitution are required. But it may be unfeasible if the protein features low stability. An interesting alternative to avoid at least reconstitution are protein powder suspensions in non-aqueous vehicles. Such formulations combine the ready-to-use approach with the high protein stability in the solid state. Additionally, protein powder suspensions offer a potentially lower viscosity compared to aqueous solutions at high protein concentrations. Besides injection, other application routes might also benefit from the protein powder approach such as topical or inhalational delivery. Protein powders, which can be dispersed in the non-aqueous suspension vehicle, are usually prepared by spray-drying or freeze-drying with an additional milling step, but other techniques have also been described in literature. An ideal powder preparation technique results in minimum protein damage and yields particle sizes in the lower micrometre range and homogeneous particle size distribution enabling subcutaneous or intramuscular injection through hypodermic needles. As suspension vehicles traditional non-aqueous injectable liquids, such as plant oils, may be selected. But they show an inherent high viscosity, which can lead to unacceptable glide forces during injection. Furthermore, the vehicle should provide high product stability with respect to protein integrity and suspension resuspendability. This review will describe how proteins can be formulated as protein powder suspensions in non-aqueous vehicles for subcutaneous injection including potential vehicles, protein powder preparation techniques, protein and suspension physical stability, as well as the use in the field of high concentration protein formulations.

Therapeutic applications of transdermal microneedles.

Transdermal drug-delivery systems (TDDS) offer an attractive alternative to the oral route for delivery of biotherapeutics. Technological advancements in the past few decades have revolutionized the fabrication of micro-structured devices including creation of microneedles (MC). These devices are used for delivering peptides, macromolecules such as proteins and DNA, and other therapeutics through the skin. Here, we review the current use of MCs as a cost effective method for the self-administration of therapeutics. We will then review the current and common use of MCs as an effective treatment strategy for a broad range of diseases and their utility in the generation of effective vaccination delivery platforms. Finally, we will summarize the currently FDA approved MCs and their applications, along with the ongoing clinical trials that use such devices.

Pentadecapeptide BPC 157 counteracts L-NAME-induced catalepsy. BPC 157, L-NAME, L-arginine, NO-relation, in the suited rat acute and chronic models resembling 'positive-like' symptoms of schizophrenia.

In the suited rat-models, we focused on the stable pentadecapeptide BPC 157, L-NAME, NOS-inhibitor, and L-arginine, NOS-substrate, relation, the effect on schizophrenia-like symptoms. Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), BPC 157 (0.01), given alone and/or together, at 5 min before the challenge for the acutely disturbed motor activity (dopamine-indirect/direct agonists (amphetamine (3.0), apomorphine (2.5)), NMDA-receptor non-competitive antagonist (MK-801 (0.2)), or catalepsy, (dopamine-receptor antagonist haloperidol (2.0)). Alternatively, BPC 157 10 µg/kg was given immediately after L-NAME 40 mg/kg intraperitoneally. To induce or prevent sensitization, we used chronic methamphetamine administration, alternating 3 days during the first 3 weeks, and challenge after next 4 weeks, and described medication (L-NAME, L-arginine, BPC 157) at 5 min before the methamphetamine at the second and third week. Given alone, BPC 157 or L-arginine counteracted the amphetamine-, apomorphine-, and MK-801-induced effect, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization. L-NAME did not affect the apomorphine-, and MK-801-induced effects, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization, but counteracted the acute amphetamine-induced effect. In combinations (L-NAME + L-arginine), as NO-specific counteraction, L-NAME counteracts L-arginine-induced counteractions in the apomorphine-, MK-801-, haloperidol- and methamphetamine-rats, but not in amphetamine-rats. Unlike L-arginine, BPC 157 maintains its counteracting effect in the presence of the NOS-blockade (L-NAME + BPC 157) or NO-system-over-stimulation (L-arginine + BPC 157). Illustrating the BPC 157-L-arginine relationships, BPC 157 restored the antagonization (L-NAME + L-arginine + BPC 157) when it had been abolished by the co-administration of L-NAME with L-arginine (L-NAME + L-arginine). Finally, BPC 157 directly inhibits the L-NAME high dose-induced catalepsy. Further studies would determine precise BPC 157/dopamine/glutamate/NO-system relationships and clinical application.

How to Increase Muscle Mass in Critically Ill Patients: Lessons Learned from Athletes and Bodybuilders.

PURPOSE OF REVIEW: Decades of research on nutrition and exercise on athletes and bodybuilders has yielded various strategies to promote anabolism and improve muscle health and growth. We reviewed these interventions in the context of muscle loss in critically ill patients. RECENT FINDINGS: For critically ill patients, ensuring optimum protein intake is important, potentially using a whey-containing source and supplemented with vitamin D and leucine. Agents like hydroxyl ß-methylbutyrate and creatine can be used to promote muscle synthesis. Polyunsaturated fatty acids stimulate muscle production as well as have anti-inflammatory properties that may be useful in critical illness. Adjuncts like oxandralone promote anabolism. Resistance training has shown mixed results in the ICU setting but needs to be explored further with specific outcomes. Critically ill patients suffer from severe proteolysis during hospitalization as well as persistent inflammation, immunosuppression, and catabolism syndrome after discharge. High protein supplementation, ergogenic aids, anti-inflammatories, and anabolic adjuncts have shown potential in alleviating muscle loss and should be used in intensive care units to optimize patient recovery.

Holistic Extractables and Leachables Program: Evaluations of Prefilled Syringe Systems for Biotechnology Products.

Prefilled syringes (PFS) are a container and delivery device of choice for storing and administering therapeutic protein products to patients. Addressing concerns and regulatory expectations related to the risk to biologic drug product quality and patient safety from PFS requires implementation of an extractable and leachable program based on understanding of materials, risk assessment, review of existing literature, and testing supported by a sound scientific foundation. Extractables and leachables data generated as part of a thorough and holistic program are presented for five PFS systems, including glass and plastic syringes filled with 12 biologic drug products encompassing the implementation of traditional and single-use biotechnology manufacturing processes. The comprehensive extractables and leachables data presented demonstrate and substantiate a holistic extractable and leachable program designed to ensure product quality and patient safety.

Strength training and protein supplementation improve muscle mass, strength, and function in mobility-limited older adults: a randomized controlled trial.

BACKGROUND: Adaptation to strength training in very old mobility-limited individuals is not fully characterized. Therefore, the aim of this study was to perform a thorough investigation of the adaptation to a lower body strength training regime in this population, with particular emphasis on the relationship between changes in selected variables. METHODS: Twenty-two mobility-limited older men and women (85 ± 6 years) were randomized to either a group performing 30 min of heavy-load strength training three times a week, with daily protein supplementation, for 10 weeks (ST), or a control group. End points were leg lean mass assessed by DXA, muscle thickness assessed by ultrasound, isometric and dynamic strength, rate of torque development, and functional capacity. RESULTS: Leg lean mass increased from baseline in ST (0.7 ± 0.3 kg), along with increased thickness of vastus lateralis (4.4 ± 3.2%), rectus femoris (6.7 ± 5.1%), and vastus intermedius (5.8 ± 5.9%). The hypertrophy was accompanied by improved knee extensor strength (20-23%) and functional performance (7-11%). In ST, neither the change in leg lean mass nor muscle thickness correlated with changes in muscle strength. However, a strong correlation was observed between the change in isometric strength and gait velocity (r = 0.70). CONCLUSIONS: The mismatch between gains in muscle size and strength suggests that muscle quality-related adaptations contributed to the increases in strength. The correlations observed between improvements in strength and function suggests that interventions eliciting large improvements in strength may also be superior in terms of functional gains in this population.

Diet composition has a differential effect on immune tolerance in insect larvae exposed to Mesorhabditis belari, Enterobacter hormaechei and its metabolites.

In insects, diet plays an important role in growth and development. Insects can vary their diet composition based on their physiological needs. In this study we tested the influence of diet composition involving varying concentrations of macronutrients and zinc on the immune-tolerance following parasite and pathogen exposure in Spodoptera litura larvae. We also tested the insecticidal potential of Mesorhabditis belari, Enterobacter hormaechei and its secondary metabolites on Spodoptera litura larvae. The results shows macronutrient composition does not directly affect the larval tolerance to nematode infection. However, Zinc supplemented diet improved the immune tolerance. While larvae exposed to bacterial infection performed better on carbohydrate rich diet. Secondary metabolites from bacteria produced an immune response in dose dependent mortality. The study shows that the larvae maintained on different diet composition show varied immune tolerance which is based on the type of infection.

Cysteine/cystine-rich undenatured whey protein supplement in patients' pressure ulcers outcomes: an open label study.

OBJECTIVE: The prevalence and costs associated with treating pressure ulcers (PU) are at high levels. Frequently, PUs heal slowly or not at all, which may be due to the patient's catabolic state which may include protein energy malnutrition. The objective of this open label clinical trial was to improve healing rates by providing patients with a patented, high-quality protein containing all essential amino acids to ensure positive nitrogen balance. An additional benefit of this protein is the delivery of bioavailable cysteine (cystine) to promote glutathione (GSH) synthesis which supports immune function and heightens antioxidant defences. METHODS: Patients with category II, III and IV PUs were fed 20g BID whey protein dietary supplement for 16-120 days, without change in ongoing 'best practice' PU management and their progress recorded. RESULTS: A total of 10 patients were recruited, with an average age of 77 years. Most had shown no improvement in healing for ≥2 months before treatment and usually had other complications including chronic obstructive pulmonary disease (COPD), diabetes and various cardiovascular diseases. There were a total of 23 PUs, with some patients having more than one. Of these, 44% (n=10) showed complete resolution 83% (n=19) had better than 75% resolution over the observation period. Healing rates ranged from 16.9-0.2cm2/month (healed PUs) and 60.0-1.6cm2/month for resolving PUs. CONCLUSION: By providing the necessary amino acids to rebuild tissues and bioactive cysteine (cystine) to promote synthesis of intracellular GSH and positive nitrogen balance, improvement in PUs healing was achieved.

Premeal Consumption of a Protein-Enriched, Dietary Fiber-Fortified Bar Decreases Total Energy Intake in Healthy Individuals.

BACKGROUND: A premeal load of protein can increase satiety and reduce energy intake. Dietary fiber also conveys metabolic benefits by modulating energy intake. We made a protein-enriched, dietary fiber-fortified bar (PFB) and aimed to investigate its effects on food intake and gut hormone secretion in healthy individuals. METHODS: Twenty subjects with normal glucose tolerance were enrolled. On three separate visits, the subjects received, in a randomized order, one of the following: a PFB containing 73 kcal with 10.7 g of protein and 12.7 g of dietary fiber; a usual bar (UB) containing the same calories as the PFB but only 0.9 g of protein and no dietary fiber; or water (control). After 15 minutes, the subjects had ad libitum intake of a test meal. Food consumption, appetite, and plasma gut hormone levels were measured. RESULTS: Total energy intake, including the bar and the test meal, was significantly reduced with the PFB preload compared to the water (904.4±534.9 kcal vs. 1,075.0±508.0 kcal, P=0.016). With the UB preload, only the intake of the test meal was reduced (P=0.044) but not the total energy intake (P=0.471) than the water. Fullness was also significantly increased after the PFB. In addition, postprandial glucose levels decreased and glucagon-like peptide-1 levels increased with the PFB compared with both the UB and water. CONCLUSION: In healthy individuals, a premeal supplementation of PFB reduced total energy intake and decreased postprandial glucose excursion. This finding necessitates long-term studies regarding clinical use in obesity.

Comparative ultrasound study of gastric emptying between an isotonic solution and a nutritional supplement / Estudo comparativo do esvaziamento gástrico entre uma solução isotônica e um suplemento nutricional por meio da ultrassonografia

Abstract Background and objectives: Preoperative fasting may lead to undesirable effects in the surgical patient in whom there is a stimulus to ingesting clear liquids until 2 hours before anesthesia. The aim of this study was to evaluate the gastric emptying of two different solutions using ultrasound. Methods: In a prospective, randomized, blind study, 34 healthy volunteers ingested 200 mL of two solutions without residues in two steps: an isotonic solution with carbohydrates, electrolytes, osmolarity of 292 mOsm.L-1, and 36 kcal; and other nutritional supplementation with carbohydrates, proteins, electrolytes, osmolarity of 680 mO.L-1, and 300 kcal. After 2 hours, a gastric ultrasound was performed to assess the antrum area and gastric volume, and the relation of gastric volume to weight (vol.w-1), whose value above 1.5 mL.kg-1 was considered a risk for bronchoaspiration. A p-value <0.05 was considered statistically significant. Results: There was a significant difference between all parameters evaluated 2 hours after the ingestion of nutritional supplementation compared to fasting. The same occurred when the parameters between isotonic solution and nutritional supplementation were compared 2 hours after ingestion. Only one patient had vol.w-1 <1.5 mL.kg-1 2 hours after ingestion of nutritional supplementation; and only one had vol.w-1 >1.5 mL.kg-1 after ingestion of isotonic solution. Conclusion: This study demonstrated that gastric emptying of equal volumes of different solutions depends on their constitution. Those with high caloric and high osmolarity, and with proteins present, 2 hours after ingestion, increased the gastric volumes, which is compatible with the risk of gastric aspiration.

Resumo Justificativa e objetivos: O jejum pré-operatório pode levar a efeitos indesejáveis no paciente cirúrgico, em que há um estimulo à ingestão de líquidos sem resíduos até 2 horas antes da anestesia. O objetivo deste estudo foi avaliar o esvaziamento gástrico de duas soluções diferentes por meio da ultrassonografia. Métodos: Em um estudo prospectivo, randomizado, cego, 34 voluntários saudáveis ingeriram 200 mL de duas soluções sem resíduos, em duas etapas: uma solução isotônica com carboidratos, eletrólitos, osmolaridade de 292 mOsm.L-1 e 36 kcal; e outra suplementação nutricional, com carboidratos, proteínas, eletrólitos, osmolaridade de 680 mOs.L-1 e 300 kcal. Após 2 horas, fez-se ultrassonografia gástrica com avaliação da área do antro e volume gástrico e relação do volume gástrico sobre o peso (vol.p-1), cujo valor acima de 1,5 mL.kg-1 foi considerado risco para broncoaspiração. Considerou-se p< 0,05 como estatisticamente significativo. Resultados: Houve diferença significativa entre todos os parâmetros avaliados 2 horas após a ingestão de suplementação nutricional em relação ao jejum. O mesmo ocorreu quando foram comparados os parâmetros entre solução isotônica e suplementação nutricional 2 horas após a ingestão. Apenas um paciente apresentou vol.p-1< 1,5 mL.kg-1 2 horas após a ingestão de suplementação nutricional; e apenas um apresentou vol.p-1 > 1,5 mL.kg-1, após a ingestão de solução isotônica. Conclusão: Este estudo demonstrou que o esvaziamento gástrico de volumes iguais de diferentes soluções depende de sua constituição. Aqueles com alto valor calórico e alta osmolaridade, e com proteínas presentes, 2 horas após a ingestão, aumentaram os volumes gástricos, compatíveis com o risco de aspiração gástrica.

Liposome-encapsulated fish oil protein-tagged gold nanoparticles for intra-articular therapy in osteoarthritis.

AIM: To provide multilayered combination therapies encompassing nanoparticles and organic peptides and to assess their efficacy in the treatment of arthritis. MATERIALS & METHODS: Fish oil protein (FP) was isolated from fish oil glands and tagged with spherical gold nanoparticles (GNPs). Tagged GNPs were encapsulated in DPPC liposomes (FP-GNP-DPPC) and characterized. RESULTS & CONCLUSION: FP increased the hydrophilicity of GNP, while encapsulation of FP-GNP within liposomes increased the hydrophobicity. In vitro release studies of FP-GNP-DPPC exhibited sustained release of FP in simulated synovial fluid. FP-GNP-DPPC injected into intra-articular joints of rats displayed anti-osteoarthritic effects in osteoarthritic rat model. This is the first study to report the anti-osteoarthritic activity of FP and DPPC encapsulated FP-GNP liposomes.

[Comparative ultrasound study of gastric emptying between an isotonic solution and a nutritional supplement]. / Estudo comparativo do esvaziamento gástrico entre uma solução isotônica e um suplemento nutricional por meio da ultrassonografia.

BACKGROUND AND OBJECTIVES: Preoperative fasting may lead to undesirable effects in the surgical patient in whom there is a stimulus to ingesting clear liquids until 2hours before anesthesia. The aim of this study was to evaluate the gastric emptying of two different solutions using ultrasound. METHODS: In a prospective, randomized, blind study, 34 healthy volunteers ingested 200mL of two solutions without residues in two steps: an isotonic solution with carbohydrates, electrolytes, osmolarity of 292 mOsm.L-1, and 36 kcal; and other nutritional supplementation with carbohydrates, proteins, electrolytes, osmolarity of 680 mO.L-1, and 300 kcal. After 2hours, a gastric ultrasound was performed to assess the antrum area and gastric volume, and the relation of gastric volume to weight (vol.w-1), whose value above 1.5mL.kg-1 was considered a risk for bronchoaspiration. A p-value <0.05 was considered statistically significant. RESULTS: There was a significant difference between all parameters evaluated 2hours after the ingestion of nutritional supplementation compared to fasting. The same occurred when the parameters between isotonic solution and nutritional supplementation were compared 2hours after ingestion. Only one patient had vol.w-1 <1.5mL.kg-1 2hours after ingestion of nutritional supplementation; and only one had vol.w-1> 1.5mL.kg-1 after ingestion of isotonic solution. CONCLUSION: This study demonstrated that gastric emptying of equal volumes of different solutions depends on their constitution. Those with high caloric and high osmolarity, and with proteins present, 2hours after ingestion, increased the gastric volumes, which is compatible with the risk of gastric aspiration.

Protein-Polymer Delivery: Chemistry from the Cold Chain to the Clinic.

Drug delivery is commonly thought of as the performance of a drug in vivo. Rather, the process of drug delivery can comprise of the journey of the drug from manufacturer to clinic, clinic to patient, and patient to disease. Each step of the journey includes hurdles that must be overcome for the therapeutic to be successful. Recent developments in proteinaceous therapeutics have made the successful completion of this journey even more important because of the relatively fragile nature of proteins in a drug delivery context. Polymers have been demonstrated to be an effective complement to proteinaceous therapeutics throughout this journey owing to their flexibility in design and function. During transit from manufacturer to clinic, the proteinaceous drug is threatened by denaturation at elevated temperatures. Polymers can help improve the thermal stability of the drug at ambient shipping conditions, thereby reducing the need for an expensive cold chain to preserve its bioactivity. Upon arrival at the clinic, the drug must be reconstituted into a suitable formulation that can be introduced into the patient. Unfortunately, traditional drug formulations relying on oral administration are generally not suitable for proteinaceous drugs owing to the hostile environment of the stomach. Other traditional methods of drug administration-like hypodermic injections-frequently suffer from low patient compliance. Polymers have been explored to design drug formulations suitable for alternative methods of administration. Upon entry into the body, proteinaceous drugs are at risk for identification, destruction, and excretion by the immune system. Polymers can help drugs reprogram immune system response and, in some cases, elicit a synergistic immune response. The next phase of research on protein-polymer-based therapeutics encourages a holistic effort to design systems that can survive each stage of the drug delivery journey.

Daily Intake of Protein from Cod Residual Material Lowers Serum Concentrations of Nonesterified Fatty Acids in Overweight Healthy Adults: A Randomized Double-Blind Pilot Study.

Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized to three experimental groups consuming tablets corresponding to 6 g/day of proteins from cod residuals as presscake meal (Cod-PC), presscake and stickwater meal (Cod-PCW), or placebo tablets (control) for eight weeks. The primary outcome of this study was changes in metabolites related to glucose regulation in overweight or obese healthy adults after intake of proteins from cod residuals. Cod-PC supplementation decreased postprandial serum nonesterified fatty acids (NEFA) concentration and increased gene expressions of diglyceride acyltransferase 1 and 2 in subcutaneous adipose tissue compared with controls. Fasting insulin increased while fasting NEFA and 120-min postprandial glucose decreased within the Cod-PC group, but these changes did not differ from the other groups. In conclusion, supplementation with Cod-PC beneficially affected postprandial serum NEFA concentration compared with the other groups in overweight or obese adults. Supplementation with Cod-PCW, which contains a higher fraction of water-soluble protein compared to Cod-PC, did not affect serum markers of glucose regulation.

Nutrition Delivery During Pediatric Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND: Macronutrient delivery during pediatric ECMO therapy can be challenging. We examined predictors of nutrient delivery in the first 2 weeks of extracorporeal membrane oxygenation (ECMO) therapy in the pediatric intensive care unit (ICU). METHODS: Details of macronutrient delivery were recorded in children (newborn-18 years of age) who survived 24 hours after cannulation to ECMO over a 3-year period (2012-2015). RESULTS: We analyzed data from 54 consecutive eligible patients, 43% female, with median (interquartile range) ECMO duration of 8.5 (6-24) days, age 0.1 (0, 16) months, ICU length of stay 32 (21, 60) days, and 28-day mortality 13%. Median weight for age z score declined from -0.1 at admission to -1.2 at 30 days (P = 0.013). At least 80% goal energy and protein was delivered in 35 (65%) and 33 (61%) patients, respectively, by day 7; 10% of energy and 11% protein goal was delivered enterally. Parenteral nutrition (PN) was utilized in 47 (87%) patients, initiated by day 1 (1, 3). Enteral nutrition (EN) was successfully delivered in 49 (94%) patients (35% postpyloric), initiated by day 6 (2, 16). Younger age (P = 0.01) and venoarterial mode of ECMO (P = 0.0014) were associated with lower EN delivery. Use of umbilical artery catheters or vasoactive infusions did not impede EN delivery. Late PN delivery was associated with cumulative protein deficits (P = 0.019) and failure to achieve nutrient delivery goals by day 7. CONCLUSIONS: Optimal nutrient delivery was achieved in most patients by day 7, predominantly via PN. Early EN is feasible in low volumes, but PN may be essential to prevent cumulative energy and protein deficits during the first week of ECMO.

Association of Energy and Protein Delivery on Skeletal Muscle Mass Changes in Critically Ill Adults: A Systematic Review.

Critically ill patients experience significant and rapid loss of skeletal muscle mass, which has been associated with negative clinical outcomes. The aetiology of muscle wasting is multifactorial and nutrition delivery may play a role. A systematic literature review was conducted to examine the association of energy and/or protein provision on changes in skeletal muscle mass in critically ill patients. Key databases were searched up until March 2016 to identify studies that measured skeletal muscle mass and/or total body protein (TBP) at 2 or more time points during acute critical illness (up to 2 weeks after an intensive care unit [ICU] stay). Studies were included if there was documentation of participant energy balance or mean energy delivered to participants during the time period between body composition measurements. Six studies met inclusion criteria. A variety of methods were used to assess skeletal muscle mass or TBP. Participants in included studies experienced differing levels of muscle loss (0%-22.5%) during the first 2 weeks of ICU admission. No association between energy and protein delivery and changes in skeletal muscle mass were observed. This review highlights that there is currently limited high-quality evidence to clearly define the association between energy and/or protein delivery and skeletal muscle mass changes in acute critical illness. Future studies in this area should be adequately powered, account for all potential confounding factors to changes in skeletal muscle mass, and detail all sources and quantities of energy and protein delivered to participants.

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Protein Supplementation to Augment the Effects of High Intensity Resistance Training in Untrained Middle-Aged Males: The Randomized Controlled PUSH Trial.

High intensity (resistance exercise) training (HIT) defined as a "single set resistance exercise to muscular failure" is an efficient exercise method that allows people with low time budgets to realize an adequate training stimulus. Although there is an ongoing discussion, recent meta-analysis suggests the significant superiority of multiple set (MST) methods for body composition and strength parameters. The aim of this study is to determine whether additional protein supplementation may increase the effect of a HIT-protocol on body composition and strength to an equal MST-level. One hundred and twenty untrained males 30-50 years old were randomly allocated to three groups: (a) HIT, (b) HIT and protein supplementation (HIT&P), and (c) waiting-control (CG) and (after cross-over) high volume/high-intensity-training (HVHIT). HIT was defined as "single set to failure protocol" while HVHIT consistently applied two equal sets. Protein supplementation provided an overall intake of 1.5-1.7 g/kg/d/body mass. Primary study endpoint was lean body mass (LBM). LBM significantly improved in all exercise groups (p ≤ 0.043); however only HIT&P and HVHIT differ significantly from control (p ≤ 0.002). HIT diverges significantly from HIT&P (p = 0.017) and nonsignificantly from HVHIT (p = 0.059), while no differences were observed for HIT&P versus HVHIT (p = 0.691). In conclusion, moderate to high protein supplementation significantly increases the effects of a HIT-protocol on LBM in middle-aged untrained males.