scholarly journals Dose‐dependent inactivation of airway tryptase with a novel dissociating anti‐tryptase antibody (MTPS9579A) in healthy participants: a randomized trial

2021 ◽  
Author(s):  
Sharon M. Rymut ◽  
Siddharth Sukumaran ◽  
Gizette Sperinde ◽  
Meire Bremer ◽  
Joshua Galanter ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Dependent Inactivation ◽  
Dose Dependent ◽  
Healthy Participants

A model of beta-adrenergic effects on calcium and potassium current in bullfrog atrial myocytes

1991 ◽  
Vol 261 (6) ◽  
pp. H1937-H1944
Author(s):  
J. M. Shumaker ◽  
J. W. Clark ◽  
W. R. Giles
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Beta Adrenergic ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Atrial Myocyte ◽  
Muscarinic Cholinergic ◽  
High Doses ◽  
Dose Dependent ◽  
Cholinergic Effects

A model of beta-adrenergic and muscarinic cholinergic effects on the bullfrog atrial myocyte has been developed to simulate the dose-dependent effects of isoprenaline (Iso) on the action potential duration (APD); i.e., low doses of Iso lengthen the APD, whereas high doses shorten the APD. In this model, the reduction in APD is the result of 1) calcium-dependent inactivation of calcium current (ICa) resulting from the enhancement of ICa by Iso and 2) an enhancement of potassium current (IK) due to both an Iso-induced increase in the rate of activation of IK and an increase in peak action potential height. The effect of acetylcholine (ACh) is simulated by a reduction in the Iso-induced increase in ICa and IK through a reduction in relative adenosine 3',5'-cyclic monophosphate concentration ([cAMP]), as well as activation of the ACh-sensitive potassium current. At low [Iso] levels in the presence of a high [ACh], the muscarinic cholinergic effects dominate the beta-adrenergic change. However, for a large [Iso] and a small [ACh], this pattern of changes in transmembrane currents is different; in this case the model predicts that ACh can actually increase APD.

scholarly journals The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial

2020 ◽  
Vol 9 (3) ◽  
pp. 375-385 ◽  
Author(s):  
Shaila Shabbir ◽  
Isabelle J. Pouliquen ◽  
Jane H. Bentley ◽  
Eric S. Bradford ◽  
Morrys C. Kaisermann ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Relative Bioavailability ◽  
Liquid Formulation ◽  
Healthy Participants

scholarly journals Oxytocin inactivates and phosphorylates rat hepatocyte glycogen synthase

1989 ◽  
Vol 261 (3) ◽  
pp. 827-830 ◽  
Author(s):  
J Ariño ◽  
F Bosch ◽  
A M Gómez-Foix ◽  
J J Guinovart
Keyword(s):  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Electrophoretic Analysis ◽  
Rat Hepatocyte ◽  
Isolated Rat Hepatocytes ◽  
Phosphorylation State ◽  
Dependent Inactivation ◽  
Cnbr Cleavage ◽  
Dose Dependent ◽  
Glycogen Synthase Activity

Incubation of isolated rat hepatocytes with oxytocin produces a time- and dose-dependent inactivation of glycogen synthase. Such inactivation is associated with an increase in the phosphorylation state of the 88 kDa subunit of the enzyme, as observed after electrophoretic analysis of the 32P-labelled enzyme isolated by immunoprecipitation from cells incubated with [32P]phosphate. CNBr cleavage of the immunoprecipitated glycogen synthase showed that multiple sites were phosphorylated after exposure of the cells to the hormone. The effect of oxytocin on hepatocyte glycogen synthase activity was not observed in the absence of extracellular Ca2+. Inactivation of glycogen synthase by oxytocin was partially abolished in the presence of insulin. These results indicate that the effects of oxytocin on glycogen synthase from rat hepatocytes are similar to those observed for other Ca2+-mediated glycogenolytic hormones, such as vasopressin.

scholarly journals Designing a Randomized Trial with an Age Simulation Suit—Representing People with Health Impairments

Healthcare ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 27
Author(s):  
Ingo J. Timm ◽  
Heike Spaderna ◽  
Stephanie C. Rodermund ◽  
Christian Lohr ◽  
Ricardo Buettner ◽  
...  
Keyword(s):  
Physical Activity ◽  
Randomized Trial ◽  
Care Services ◽  
The People ◽  
Adequate Care ◽  
Professional Care ◽  
Increasing Demand ◽  
Age Simulation ◽  
Health Impairments ◽  
Healthy Participants

Due to demographic change, there is an increasing demand for professional care services, whereby this demand cannot be met by available caregivers. To enable adequate care by relieving informal and formal care, the independence of people with chronic diseases has to be preserved for as long as possible. Assistance approaches can be used that support promoting physical activity, which is a main predictor of independence. One challenge is to design and test such approaches without affecting the people in focus. In this paper, we propose a design for a randomized trial to enable the use of an age simulation suit to generate reference data of people with health impairments with young and healthy participants. Therefore, we focus on situations of increased physical activity.

Nisin Treatment To Enhance the Efficacy of Gamma Radiation against Listeria monocytogenes on Meat

2011 ◽  
Vol 74 (2) ◽  
pp. 193-199 ◽  
Author(s):  
HUSSEIN M. H. MOHAMED ◽  
FATHI A. ELNAWAWI ◽  
AHMED E. YOUSEF
Keyword(s):  
Listeria Monocytogenes ◽  
Gamma Radiation ◽  
Foodborne Pathogens ◽  
Antimicrobial Effect ◽  
Most Probable Number ◽  
Probable Number ◽  
Raw Meat ◽  
Dependent Inactivation ◽  
Low Levels ◽  
Dose Dependent

Treatment of meat with gamma radiation for inactivation of foodborne pathogens might cause undesirable quality changes in the product. The objective of the present study was to use nisin for enhancing the lethality of gamma radiation against Listeria monocytogenes, so that moderate doses of radiation can effectively eliminate the pathogen on meat. Cubes of raw meat (10 g each) were inoculated with L. monocytogenes (107CFU/g) and treated with nisin (103 IU/g), gamma radiation (0.25 to 1.5 kGy), or combinations of these treatments. Meat was analyzed for L. monocytogenes survivors immediately after treatment and during storage at 4°C for up to 72 h. Nisin treatment alone inactivated L. monocytogenes by 1.2 log CFU/g. Gamma radiation caused dose-dependent inactivation of the pathogen. Treatment with combinations of nisin and gamma radiation resulted in an additive antimicrobial effect when inoculated meat was tested during the first 24 h and in a synergistic effect when tested after 72 h of storage at 4°C. When L. monocytogenes was inoculated onto meat at low levels (4 × 103CFU/g), treated with nisin (103 IU/g), and then irradiated (1.5 kGy) and stored at 4°C for 72 h, the pathogen's most probable number was <0.03/g, indicating that such a combination is potentially effective in eliminating L. monocytogenes in meat.

Intensity-dependent effect of pulsed and continuous therapeutic ultrasound on endothelial function: a randomised crossover clinical trial

2019 ◽  
Vol 26 (12) ◽  
pp. 1-12
Author(s):  
Melina Hauck ◽  
Felipe da Silva Paulitsch ◽  
Jeferson Mendez Cruz ◽  
Cassio Noronha Martins ◽  
Murilo Rezende Oliveira ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Therapeutic Ultrasound ◽  
Flow Mediated Dilation ◽  
Pulsed Ultrasound ◽  
Additional Increase ◽  
Dependent Effect ◽  
Baseline Values ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Healthy Participants

Background/Aims The aim of this study was to evaluate the effects of different intensities and waveforms of therapeutic ultrasound on endothelial function in typically healthy participants. Methods A total of 15 participants were evaluated over 2 consecutive days. Different intensities of continuous and pulsed (20% duty cycle) 1-MHz ultrasound were applied to the brachial artery for 5 minutes each. Endothelial function was measured using flow-mediated dilation technique before and immediately after ultrasound was applied. Results Compared to baseline values, endothelium-dependent vasodilation increased with both continuous (2.8%) and pulsed (1.6%) ultrasound at an intensity of 0.4 W/cm2SPTA. At 1.2 W/cm2SPTA, endothelium-dependent vasodilation was 4.1% above baseline for pulsed and 5.3% above baseline for continuous waveforms. There was no additional increase in vasodilation at intensities above 1.2 W/cm2SPTA. The percentage of endothelium-dependent vasodilation was similar for the all of the different waveforms studied. Conclusions Both continuous and pulsed ultrasound waveforms promote endothelium-dependent vasodilation. There was a dose-dependent increase in vasodilation at intensities from 0.4 W/cm2SPTA to 1.2 W/cm2SPTA. Pulsed is more efficient than continuous ultrasound because it produces the same effect on endothelium-dependent vasodilation while employing 20% of the energy applied with continuous ultrasound.

scholarly journals Photodynamic inactivation of prions by disulfonated hydroxyaluminium phthalocyanine

2012 ◽  
Vol 93 (11) ◽  
pp. 2512-2517 ◽  
Author(s):  
Olga Janouskova ◽  
Jan Rakusan ◽  
Marie Karaskova ◽  
Karel Holada
Keyword(s):  
Fungal Infections ◽  
Brain Homogenate ◽  
Normal Pressure ◽  
Disodium Salt ◽  
Photodynamic Inactivation ◽  
Dependent Inactivation ◽  
Photodynamic Activity ◽  
Sulfonated Phthalocyanines ◽  
Dose Dependent

Sulfonated phthalocyanines (Pcs) are cyclic tetrapyrroles that constitute a group of photosensitizers. In the presence of visible light and diatomic oxygen, Pcs produce singlet oxygen and other reactive oxygen species that have known degradation effects on lipids, proteins and/or nucleic acids. Pcs have been used successfully in the treatment of bacterial, yeast and fungal infections, but their use in the photodynamic inactivation of prions has never been reported. Here, we evaluated the photodynamic activity of the disodium salt of disulfonated hydroxyaluminium phthalocyanine (PcDS) against mouse-adapted scrapie RML prions in vitro. PcDS treatment of RML brain homogenate resulted in a time- and dose-dependent inactivation of prions. The photodynamic potential of Pcs offers a new way to inactivate prions using biodegradable compounds at room temperature and normal pressure, which could be useful for treating thermolabile materials and liquids.

scholarly journals Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans

2015 ◽  
Vol 115 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Marina Coletta ◽  
Fred K. Gates ◽  
Luca Marciani ◽  
Henna Shiwani ◽  
Giles Major ◽  
...  
Keyword(s):  
Gas Content ◽  
Gluten Free ◽  
Open Label ◽  
Healthy Humans ◽  
Gluten Content ◽  
Gi Symptoms ◽  
Mri Scans ◽  
Mri Study ◽  
Dose Dependent ◽  
Healthy Participants

AbstractGluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (sem96)v. 212 (sem74)v. 179 (sem87) ml, respectively;P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5);P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

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