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Cell Reports. Medicine Dec 2023The belief that the anabolic response to feeding during postexercise recovery is transient and has an upper limit and that excess amino acids are being oxidized lacks...
The belief that the anabolic response to feeding during postexercise recovery is transient and has an upper limit and that excess amino acids are being oxidized lacks scientific proof. Using a comprehensive quadruple isotope tracer feeding-infusion approach, we show that the ingestion of 100 g protein results in a greater and more prolonged (>12 h) anabolic response when compared to the ingestion of 25 g protein. We demonstrate a dose-response increase in dietary-protein-derived plasma amino acid availability and subsequent incorporation into muscle protein. Ingestion of a large bolus of protein further increases whole-body protein net balance, mixed-muscle, myofibrillar, muscle connective, and plasma protein synthesis rates. Protein ingestion has a negligible impact on whole-body protein breakdown rates or amino acid oxidation rates. These findings demonstrate that the magnitude and duration of the anabolic response to protein ingestion is not restricted and has previously been underestimated in vivo in humans.
Topics: Humans; Post-Exercise Recovery; Amino Acids; Muscle, Skeletal; Eating; GTP-Binding Proteins
PubMed: 38118410
DOI: 10.1016/j.xcrm.2023.101324 -
Nature Reviews. Endocrinology Aug 2023Tremendous progress has been made towards achieving tight glycaemic control in individuals with diabetes mellitus through the use of frequent or continuous glucose... (Review)
Review
Tremendous progress has been made towards achieving tight glycaemic control in individuals with diabetes mellitus through the use of frequent or continuous glucose measurements. However, in patients who require insulin, accurate dosing must consider multiple factors that affect insulin sensitivity and modulate insulin bolus needs. Accordingly, an urgent need exists for frequent and real-time insulin measurements to closely track the dynamic blood concentration of insulin during insulin therapy and guide optimal insulin dosing. Nevertheless, traditional centralized insulin testing cannot offer timely measurements, which are essential to achieving this goal. This Perspective discusses the advances and challenges in moving insulin assays from traditional laboratory-based assays to frequent and continuous measurements in decentralized (point-of-care and home) settings. Technologies that hold promise for insulin testing using disposable test strips, mobile systems and wearable real-time insulin-sensing devices are discussed. We also consider future prospects for continuous insulin monitoring and for fully integrated multisensor-guided closed-loop artificial pancreas systems.
Topics: Humans; Insulin; Diabetes Mellitus, Type 1; Blood Glucose; Insulin Infusion Systems; Insulin Resistance; Pancreas, Artificial; Blood Glucose Self-Monitoring; Hypoglycemic Agents
PubMed: 37217746
DOI: 10.1038/s41574-023-00842-3 -
Journal of Aerosol Medicine and... Aug 2023In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as...
In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as bronchodilators or antibiotics are needed, vasodilator therapy may be interrupted. This study assesses aerosol systems designed for simultaneous delivery of two aerosols using continuous nebulization and bolus injection without interruption or circuit disconnection. One i dual-port breath-enhanced jet nebulizer (BEJN) or two Aerogen Solo vibrating mesh nebulizers (VMNs) were installed on the dry side of the humidifier. VMN were stacked; one for infusion and the second for bolus drug delivery. The BEJN was powered by air at 3.5 L/min, 50 psig. Radiolabeled saline was infused at 5 and 10 mL/h with radiolabeled 3 and 6 mL bolus injections at 30 and 120 minutes, respectively. Two adult breathing patterns (duty cycle 0.13 and 0.34) were tested with an infusion time of 4 hours. Inhaled mass (IM) expressed as % of initial syringe activity (IM%/min) was monitored in real time with a ratemeter. All delivered radioaerosol was collected on a filter at the airway opening. Transients in aerosol delivery were measured by calibrated ratemeter. IM%/h during continuous infusion was linear and predictable, mean ± standard deviation (SD): 2.12 ± 1.45%/h, 2.47 ± 0.863%/h for BEJN and VMN, respectively. BEJN functioned without incident. VMN continuous aerosol delivery stopped spontaneously in 3 of 8 runs (38%); bolus delivery stopped spontaneously in 3 of 16 runs (19%). Tapping restarted VMN function during continuous and bolus delivery runs. Bolus delivery IM% (mean ± SD): 20.90% ± 7.01%, 30.40% ± 11.10% for BEJN and VMN, respectively. Simultaneous continuous and bolus nebulization without circuit disconnection is possible for both jet and mesh technology. Monitoring of VMN devices may be necessary in case of spontaneous interruption of nebulization.
Topics: Adult; Humans; Respiration, Artificial; Administration, Inhalation; Albuterol; Aerosols; Nebulizers and Vaporizers; Bronchodilator Agents; Drug Delivery Systems; Equipment Design
PubMed: 37256713
DOI: 10.1089/jamp.2022.0057 -
Translational Psychiatry May 2023N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing... (Randomized Controlled Trial)
Randomized Controlled Trial
N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use of intravenous DMT, data are lacking on its clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial in 27 healthy participants to test different intravenous DMT administration regimens: placebo, low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus + low infusion (15 mg + 0.6 mg/min), and high bolus + high infusion (25 mg + 1 mg/min). Study sessions lasted for 5 h and were separated by at least 1 week. Participant's lifetime use of psychedelics was ≤20 times. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics of DMT, and plasma levels of brain-derived neurotropic factor (BDNF) and oxytocin. Low (15 mg) and high (25 mg) DMT bolus doses rapidly induced very intense psychedelic effects that peaked within 2 min. DMT infusions (0.6 or 1 mg/min) without a bolus induced slowly increasing and dose-dependent psychedelic effects that reached plateaus after 30 min. Both bolus doses produced more negative subjective effects and anxiety than infusions. After stopping the infusion, all drug effects rapidly decreased and completely subsided within 15 min, consistent with a short early plasma elimination half-life (t) of 5.0-5.8 min, followed by longer late elimination (t = 14-16 min) after 15-20 min. Subjective effects of DMT were stable from 30 to 90 min, despite further increasing plasma concentrations, thus indicating acute tolerance to continuous DMT administration. Intravenous DMT, particularly when administered as an infusion, is a promising tool for the controlled induction of a psychedelic state that can be tailored to the specific needs of patients and therapeutic sessions.Trial registration: ClinicalTrials.gov identifier: NCT04353024.
Topics: Humans; N,N-Dimethyltryptamine; Hallucinogens; Healthy Volunteers; Administration, Intravenous; Anxiety
PubMed: 37221177
DOI: 10.1038/s41398-023-02477-4