An analysis of errors in estimation of the rate of protein synthesis by constant infusion of a labelled amino acid.
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ABSTRACT:
SUBMITTER: Garlick PJ
PROVIDER: S-EPMC1186247 | biostudies-other | 1978 Nov
REPOSITORIES: biostudies-other
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Project description:We developed a software for extraction of protein decay rate constants from heavy water labeling followed by LC-MS experiments. We illustrate the program on application to normal diet and western diet fed LDLR-/- mice. We demonstrate that proteins subunits of 40S ribosomal complex have reduced stability in western diet fet mice.
2019-04-10 | PXD009493 | Pride
Project description:BackgroundThe inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure.ResultsIn the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups.ConclusionsThe pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.
| S-EPMC10709979 | biostudies-literature
Project description:BackgroundConventional intravenous patient-controlled analgesia (PCA), which usually involves constant-rate background infusion plus demand dosing, may cause adverse effects or insufficient analgesia. When variable-rate feedback infusion plus demand dosing mode is used, the infusion rate can be changed according to the patient's needs.MethodsIn this prospective randomized double-blind study, 78 adults who were undergoing spinal fusion surgery were randomly allocated to either the constant-rate background infusion plus demand dosing group (group C) or the variable-rate feedback infusion plus demand dosing group (group V). The number of demands, volume delivered, numerical rating scale (NRS) score, adverse effects and the use of rescue analgesics were examined at 30 minutes after the operation in the post-anesthesia care unit, and at 6, 12, 24, and 48 hours.ResultsThe number of demands was significantly lower in group V than in group C at 12-24 hours (4.59 ± 4.31 vs 9.21 ± 6.79 times, P = .001) and over the total period. The volume delivered via PCA was significantly lower in group V than in group C at 12 to 24 hours (13.96 ± 13.45 vs 21.19 ± 8.66 mL, P = .006), 24 to 48 hours (13.39 ± 12.44 vs 33.6 ± 12.49 mL, P = .000), and over the total period. NRS scores, administration of rescue analgesics, and postoperative nausea and vomiting showed no between-group differences.ConclusionsVariable-rate feedback infusion plus the demand dosing mode can control postoperative pain more efficiently, with lower dosages of analgesics, than constant-rate background infusion plus demand dosing in patients who undergo spinal fusion surgery.
| S-EPMC6417619 | biostudies-literature
Project description:We present the Rate from Event Durations (RED) scheme, a new scheme that more efficiently calculates rate constants using the weighted ensemble path sampling strategy. This scheme enables rate-constant estimation from shorter trajectories by incorporating the probability distribution of event durations, or barrier-crossing times, from a simulation. We have applied the RED scheme to weighted ensemble simulations of a variety of rare-event processes that range in complexity: residue-level simulations of protein conformational switching, atomistic simulations of Na+/Cl- association in explicit solvent, and atomistic simulations of protein-protein association in explicit solvent. Rate constants were estimated with up to 50% greater efficiency than the original weighted ensemble scheme. Importantly, our scheme accounts for the systematic error that results from statistical bias toward the observation of events with short durations and reweights the event duration distribution accordingly. The RED scheme is relevant to any simulation strategy that involves unbiased trajectories of similar length to the most probable event duration, including weighted ensemble, milestoning, and standard simulations as well as the construction of Markov state models.
| S-EPMC7972523 | biostudies-literature
Project description:An equation was derived from which the turnover time of individual muscle proteins could be calculated from measurements made at a single time interval in individual animals after initiation of constant intravenous infusion of labelled amino acid. The calculation requires only the specific radioactivities of the amino acid in plasma, in the intracellular fluid and in the protein under study. Pool sizes were not required. When the equation was applied to adult guinea-pig cardiac myosin, the average turnover time was 16 +/- 1 days.
| S-EPMC1183879 | biostudies-other
Project description:ObjectivesThe purpose of this study was to determine whether or not fluorescence could be increased by administering indocyanine green at a constant rate, thus stabilizing its blood concentration.MethodsIn 20 consecutive patients undergoing segmentectomy, the dominant pulmonary arteries were ligated, blocking blood in the target segment. Fluorescence intensity was then observed using different indocyanine green administration methods under infrared thoracoscopy. Intravenous administration of indocyanine green, via a syringe pump at a rate of 12.5 mg/min, was defined as the constant rate group. The bolus group was defined by a 5-mg indocyanine green rapid intravenous injection. The fluorescence intensity was compared at the time of maximum fluorescence and 2 minutes after fluorescence initiation.ResultsAt maximum staining, the fluorescence intensity of the normal blood flow area was brighter in the constant rate group (median, 184.2; interquartile range, 170.2-200.1) compared with the bolus group (median, 122.3; interquartile range, 87.3-144.7; P = .0003). The fluorescence of the normal blood flow was retained even after 2 minutes. There was no difference in the fluorescence intensity of the ischemic segments.ConclusionsThe constant rate method showed brighter and better fluorescence than the bolus injection, without an increase in the dose. The contrast between adjacent segments was clear, facilitating the differentiation of the areas.
| S-EPMC8302929 | biostudies-literature
Project description:Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or both, in standing horses. A prospective, blind, randomized crossover, experimental design with six healthy adult horses was performed, in which four treatments were administered to all horses with at least two weeks of washout period: medetomidine (M); medetomidine and ketamine (MK); medetomidine and morphine (MMo); and medetomidine, morphine and ketamine (MMoK). Dosages were the same in all treatment groups: medetomidine at 5 µg/kg bwt followed by 5 µg/kg bwt/h, ketamine at 0.4 mg/kg/h and morphine at 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h. Drug infusions were maintained for 120 min. Cardiorespiratory variables, sedation degree and antinociceptive effects were evaluated during the procedure. All combinations produced similar sedation and antinociceptive effects and no clinically relevant alterations in cardiorespiratory variables occurred. Medetomidine CRI combined with morphine, ketamine or both are suitable and safe protocols for standing sedation in horses and the addition of morphine and/or ketamine did not cause any negative effect but no improving effect on sedation and antinociception was detected.
| S-EPMC8300393 | biostudies-literature
Project description:IntroductionConstant rate infusion (CRI) of benzodiazepines or propofol (PPF) is a therapeutic option for cluster seizures (CS) and status epilepticus (SE) in canine patients non-responding to first-line benzodiazepines or non-anesthetics. However, specific indications for optimal duration of CRI are lacking. The aim of this study was to determine the effect of duration of anesthetic CRI on outcome and length of hospital stay in dogs with refractory seizure activity of different etiology.Study designOpen-label non-randomized clinical trial.Materials and methodsSeventy-three client-owned dogs were enrolled. Two groups [experimental (EXP) vs. control (CTRL)] were compared. The EXP group received diazepam (DZP) or PPF CRI for 12 h (±1 h) and the CTRL group received DZP or PPF CRI for 24 h (±1 h) in addition to a standardized emergency treatment protocol identical for both study groups. The historical control group was made up of a population of dogs already reported in a previously published paper by the same authors. Favorable outcome was defined as seizure cessation after CRI, no seizure recurrence, and clinical recovery. Poor outcome was defined as seizure recurrence, death in hospital or no return to acceptable clinical baseline. Univariate statistical analysis was performed.ResultsThe study sample was 73 dogs: 45 (62%) received DZP CRI and 28 (38%) received PPF CRI. The EXP group was 39 dogs (25 DZP CRI and 14 PPF CRI) and the CTRL group 34 dogs (20 DZP CRI and 14 PPF CRI). We found no statistically significant difference in outcomes between the groups. The median length of stay was 56 h (IQR, 40-78) for the ALL EXP group and 58.5 h (IQR, 48-74.5) for the ALL CTRL group (p = 0.8).ConclusionEven though a shorter DZP or PPF CRI duration was not associated with a worse outcome, the study failed to identify a clear superiority of shorter CRI duration on outcome or length of hospital stay in dogs with refractory seizure activity of different etiology.
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Project description:In unicellular organisms, growth rate is the major phenotype that is being selected through evolution. In order to grow efficiently, living cells should synchronize the quantity of their ribosome and RNA polymerase levels according to the respective rates by which amino acids and nucleotides pool are replenished. Gene expression patterns and their relationship with growth rate have been widely investigated in various conditions, and a large set of transcripts which included genes associated with ribosome biogenesis (Ribi) and with the stress response, was shown to be expressed in coordination with cell growth rate. Interestingly, decoupling of this correlation was found for certain mutants and conditions, including in my lab when mutant growth rate was examined and when yeast were grown on xylulose, a carbon source not available in the wild. Under those conditions, amino-acid biosynthesis genes regulated by the GCN4 transcription factor were found to have a strong inverse correlation with growth rate, while Ribi and stress genes showed no such correlation. I hypothesized that this decoupling of the general coupling between growth rate and gene expression is a result of a lack of evolutionary optimization to this carbon source or to genetic mutations. The goal of my study was to examine this hypothesis at a greater depth. To this end, I defined the growth rate and genome-wide expression profile of 328 strains deleted of individual genes that show different levels of growth defect. As predicted, growth rate of those strains was correlated with the expression level of GCN4-dependent genes, but not with the Ribi or stress genes, similar to the correlation observed in our xylulose experiment. 328 S. Cerevisiae deletion strains relatively to the wild type strain
2014-02-07 | E-GEOD-54748 | biostudies-arrayexpress
Project description:Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005), and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16 vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29 micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C), release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(-1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x min(-1) x kg(-1)) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.
| S-EPMC2739698 | biostudies-literature