Theophylline minimally alters contractile properties of canine diaphragm in vitro

1990 ◽  
Vol 69 (4) ◽  
pp. 1390-1396 ◽  
Author(s):  
E. Derom ◽  
S. Janssens ◽  
V. De Bock ◽  
M. Decramer
Keyword(s):  
High Frequency ◽  
Force Production ◽  
Contractile Properties ◽  
Diaphragm Muscle ◽  
Muscle Bundle ◽  
Time To Peak ◽  
Diaphragm In Vitro ◽  
Tetanic Tension

We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High-frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.

Adaptability of the hamster diaphragm to exercise and/or emphysema

1982 ◽  
Vol 53 (5) ◽  
pp. 1263-1272 ◽  
Author(s):  
G. A. Farkas ◽  
C. Roussos
Keyword(s):  
Contractile Properties ◽  
Force Frequency ◽  
Control Groups ◽  
Optimal Length ◽  
Time To Peak ◽  
Residual Capacity ◽  
Vitro Analysis ◽  
Tetanic Tension ◽  
In Vitro Analysis

In vitro contractile properties of the diaphragm were measured in four groups of inbred adult hamsters (greater than 40wk), randomly divided into sedentary control (SC), exercise control (EC), sedentary emphysematous (SE), and exercise emphysematous (EE) groups. Emphysema was induced by a single endotracheal instillation of elastase. Exercise consisted of running 1 h/day, 7 days/wk for 20 wk. Functional residual capacity (FRC), measured by means of a pressure box, was approximately 2.5 times greater in both emphysematous groups compared with control groups. Small diaphragmatic bundles were then isolated and subjected to in vitro analysis of isometric contractile properties. No differences were observed among the four groups in time to peak tension, half-relaxation time, and shape of the force-frequency curve. The diaphragmatic length-tension curve of emphysematous animals was displaced toward the left; maximal tetanic tension was similar in all groups, while optimal length (Lo), defined as the length at which maximal twitch tension occurred, was significantly shorter in both emphysematous groups. The Lo was negatively correlated with the FRC. Exercise tended to increase the in vitro endurance of the diaphragm bundles in control animals only. Diaphragms from both emphysematous groups, however, did show the greatest resistance to fatigue. It is concluded that 1) daily running for 1 h does not influence the diaphragmatic contractile properties in the hamster, but fatigue was reduced; 2) the load of chronic emphysema decreased the hamster's diaphragm fatiguability; and 3) the diaphragms of emphysematous hamsters chronically adapt by decreasing diaphragmatic length in proportion to the degree of hyperinflation and thus probably continue to operate at an Lo.

THE WATER AND ELECTROLYTE METABOLISM OF RAT DIAPHRAGM IN VITRO

1956 ◽  
Vol 34 (1) ◽  
pp. 1069-1083 ◽  
Author(s):  
R. H. Rixon ◽  
J. A. F. Stevenson
Keyword(s):  
Intracellular Water ◽  
Diaphragm Muscle ◽  
Optimal Conditions ◽  
Rat Diaphragm ◽  
Concentration Gradients ◽  
Hypoxic Conditions ◽  
Diaphragm In Vitro ◽  
Sodium And Potassium

The distribution of water and of sodium and potassium between the cell and synthetic environments has been studied in rat diaphragm muscle. It has been found that: (1) the amount of intracellular water is markedly increased at 0 °C. in oxygen and at 37 °C. in nitrogen compared to that of tissue at 37 °C. in oxygen, in media up to 0.75 osmolar; (2) optimal conditions of temperature and oxygen are necessary to prevent or reduce the uptake of water; (3) swelling at reduced temperatures and under hypoxic conditions is related to the oxygen uptake; (4) the loss of tissue solids during incubation does not have any significant effect on the calculation of the total tissue and intracellular water; (5) the concentration of total sodium and potassium in the tissue, in vivo and in vitro at optimal conditions is slightly in excess of that in the plasma water or incubating medium—this is believed not to represent an active hypertonicity; (6) concomitant with the uptake of water there are marked redistributions of sodium and potassium, the gain of sodium being greater than the loss of potassium. It is concluded that the swelling of tissue cells under conditions that inhibit oxidative metabolism is primarily due to the redistribution of electrolytes and that the natural distribution of water in muscle is determined by active maintenance of the concentration gradients of sodium and potassium across the cell membrane.

THE WATER AND ELECTROLYTE METABOLISM OF RAT DIAPHRAGM IN VITRO

1956 ◽  
Vol 34 (5) ◽  
pp. 1069-1083 ◽  
Author(s):  
R. H. Rixon ◽  
J. A. F. Stevenson
Keyword(s):  
Intracellular Water ◽  
Diaphragm Muscle ◽  
Optimal Conditions ◽  
Rat Diaphragm ◽  
Concentration Gradients ◽  
Hypoxic Conditions ◽  
Diaphragm In Vitro ◽  
Sodium And Potassium

The distribution of water and of sodium and potassium between the cell and synthetic environments has been studied in rat diaphragm muscle. It has been found that: (1) the amount of intracellular water is markedly increased at 0 °C. in oxygen and at 37 °C. in nitrogen compared to that of tissue at 37 °C. in oxygen, in media up to 0.75 osmolar; (2) optimal conditions of temperature and oxygen are necessary to prevent or reduce the uptake of water; (3) swelling at reduced temperatures and under hypoxic conditions is related to the oxygen uptake; (4) the loss of tissue solids during incubation does not have any significant effect on the calculation of the total tissue and intracellular water; (5) the concentration of total sodium and potassium in the tissue, in vivo and in vitro at optimal conditions is slightly in excess of that in the plasma water or incubating medium—this is believed not to represent an active hypertonicity; (6) concomitant with the uptake of water there are marked redistributions of sodium and potassium, the gain of sodium being greater than the loss of potassium. It is concluded that the swelling of tissue cells under conditions that inhibit oxidative metabolism is primarily due to the redistribution of electrolytes and that the natural distribution of water in muscle is determined by active maintenance of the concentration gradients of sodium and potassium across the cell membrane.

Effects of fatigue on the length-tetanic force relationship of the rat diaphragm

1993 ◽  
Vol 74 (1) ◽  
pp. 326-332 ◽  
Author(s):  
A. P. Gauthier ◽  
R. E. Faltus ◽  
P. T. Macklem ◽  
F. Bellemare
Keyword(s):  
High Frequency ◽  
Force Production ◽  
High Frequency Stimulation ◽  
Control Force ◽  
Optimal Length ◽  
Tetanic Force ◽  
Wide Range ◽  
Force Relationship

It has been established that the in vivo operating length of the diaphragm corresponds to a wide range of the ascending limb of its length-tetanic force relationship. To investigate the length-dependent effects of fatigue on maximum force production, we constructed length-tetanic force relationships of rat costal diaphragm strips in vitro before and after fatigue induced by repetitive supramaximal electrical field stimulations at optimal length. Two levels of fatigue were studied (i.e., force reductions of 40 and 65% at optimal length). Results indicate that fatigue, when evaluated with high-frequency stimulations, causes a proportionately larger decrease in tetanic force at short muscle lengths as seen by a smaller control force-to-fatigue force ratio and an apparent shift in the length at which active force is zero. A possible explanation for the results obtained is failure of propagation of membrane depolarization into the t-tubule system at short muscle lengths, which is aggravated by fatigue evaluated by high-frequency stimulation.

scholarly journals Selective elimination of immunosuppressive T cells in patients with multiple myeloma

Leukemia ◽  
2021 ◽  
Author(s):  
Mohamed H. S. Awwad ◽  
Abdelrahman Mahmoud ◽  
Heiko Bruns ◽  
Hakim Echchannaoui ◽  
Katharina Kriegsmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Immune Responses ◽  
High Frequency ◽  
Surface Markers ◽  
Selective Elimination ◽  
Related Transcription Factor ◽  
Cell Membrane Protein

AbstractElimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8+CD28-CD57+ Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26–35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7+CD8+ T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8+ Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

scholarly journals High Frequency Plant Regeneration of Musa paradisiaca cv. Karibale Monthan

2015 ◽  
Vol 3 (2) ◽  
pp. 202-209 ◽  
Author(s):  
R. Shashi Kumar ◽  
V. Krishna ◽  
. Venkatesh
Keyword(s):  
Plant Regeneration ◽  
High Frequency ◽  
Synergetic Effect ◽  
Multiple Shoot ◽  
Coconut Water ◽  
Morphological Variations ◽  
Musa Paradisiaca ◽  
Shoot Initiation

High frequency plant regeneration protocol has been standardized from banana cultivar Musa paradisiaca cv. Karibale Monthan, an endemic cultivar of Malnad region of Karnataka. The fruits are used as glomerular protective to solve kidney problems. To minimize the microbial contamination and to promote healthy growth, explants were treated with 70 % absolute alcohol for 6 min, 0.1 % Mercuric chloride for 10 min and 0.2 % for 10 min, 1 % Sodium hypochlorite for 15 min, 0.1 % Cefotaxime for 5 min and 0.05 % Gentamicin for 5 min. The high frequency shoot initiation (93.33 %) was recorded at 5 mg/l BAP. The synergetic effect of BAP (4 to 6 mg/l), TDZ (0.1 to 1.2 mg/l) and coconut water (0.1 to 0.9 ml/l) induced multiple shoot buds and it was optimized at the concentration of 5 mg/l BAP, 0.5 mg/l TDZ and 0.5 ml/l coconut water with 15.90 ± 1.66 frequency of shoots per propagule. Supplementation of 1.0 mg/l IBA induced 5.33 ± 1.21 numbers of roots with a mean root length of 7.50 ± 1.87 roots. The 99% of plantlets with distinct roots and shoots were successfully acclimatized in the green house and transferred to the field to evaluate the agro-morphological variations. The weight of the bunch (kg), number of hands in a bunch, number of fingers in a hand, length of the finger (cm), girth of the finger (cm) and girth of the pseudostem (cm) exhibited by in vitro plants were higher than the in vivo plants.Int J Appl Sci Biotechnol, Vol 3(2): 202-209 DOI: http://dx.doi.org/10.3126/ijasbt.v3i2.12536 

scholarly journals Single- and Multiple-Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of the Polymyxin Derivative, SPR206

2021 ◽  
Author(s):  
Jon Bruss ◽  
Troy Lister ◽  
Vipul K. Gupta ◽  
Emily Stone ◽  
Lisa Morelli ◽  
...  
Keyword(s):  
Systemic Exposure ◽  
Multidrug Resistant ◽  
Double Blind ◽  
Important Species ◽  
Time To Peak ◽  
Extended Spectrum Beta Lactamases ◽  
Dose Study ◽  
Control And Prevention

Carbapenem-resistant Acinetobacter baumannii and Enterobacterales are identified as urgent threats, and multidrug-resistant (MDR) Pseudomonas aeruginosa and extended-spectrum beta-lactamases (ESBL)-producing pathogens are identified as a serious threat by the Centers for Disease Control and Prevention (CDC). SPR206 is a novel polymyxin derivative with potent in vitro and in vivo activity against A. baumannii , P. aeruginosa , and multiple clinically important species of Enterobacterales, including multidrug- and extensively drug-resistant strains. This was a first-in-human (FIH) double-blind, placebo-controlled, single- and multiple ascending dose study of the safety, tolerability, and pharmacokinetics (PK) of SPR206 in 94 healthy subjects. Following IV administration (1 h infusion) at single doses of 10 mg to 400 mg and multiple doses of 25 mg to 150 mg q8h for 7 days and 100 mg q8h for 14 days, SPR206 was generally safe and generally well tolerated. While the incidence of adverse events increased with dose, most were of mild severity. Systemic exposure (C max and AUC) to SPR206 was approximately dose proportional, time to peak concentrations ranged from 1.1 to 1.3 hours, and half-life ranged from 2.4 to 4.1 hours. No appreciable accumulation occurred with repeated dosing of SPR206 and trough concentrations suggest that steady state was achieved by Day 2. Urinary excretion of unchanged SPR206 was dose dependent across single- (SAD) and multiple ascending dose (MAD) cohorts, and the percentage of dose excreted as SPR206 was up to >50%. Importantly, no evidence of nephrotoxicity was observed over 14 days of 100 mg q8h dosing of SPR206; a dosing regimen anticipated to exceed requirements for clinical efficacy.

Hydrogen Evolution Catalyzed by Hydrogenase in Cultures of Cyanobacteria

1981 ◽  
Vol 36 (1-2) ◽  
pp. 87-92 ◽  
Author(s):  
Patrick C. Hallenbeck ◽  
Leon V. Kochian ◽  
John R. Benemann
Keyword(s):  
Hydrogen Production ◽  
Hydrogen Evolution ◽  
High Frequency ◽  
Nitrogenase Activity ◽  
Inhibitory Effect ◽  
Hydrogenase Activity ◽  
Oxygen Inhibition ◽  
Oxygen Sensitive

Abstract Cultures of Anabaena cylindrica, grown on media containing 5 mᴍ NH4Cl (which represses heterocyst formation), evolved hydrogen after a period of dark incubation under an argon atmosphere. This hydrogen production was not due to nitrogenase activity, which was nearly undetectable, but was due to a hydrogenase. Cultures grown on media with tungsten substituted for molybdenum had a high frequency of heterocysts (15%) and inactive nitrogenase after nitrogen starvation. The hydrogenase activity of these cultures was three-fold greater than the activity of non-heterocystous cultures. The effects of oxygen inhibition on hydrogen evolution by hetero-cystous cultures suggest that two pools of hydrogenase activity exist - an oxygen sensitive hydrogen evolution in vegetative cells and a relatively oxygen-resistent hydrogen evolution in heterocysts. In either case, inhibition by oxygen was reversible. Light had an inhibitory effect on net hydrogen evolution. Hydrogen production in vitro was much higher than in vivo, indicating that in vivo hydrogenase activity is limited by endogenous reductant supply.

Effect of dichloroacetate on mechanical performance and metabolism of compromised diaphragm muscle

1992 ◽  
Vol 72 (3) ◽  
pp. 1149-1155 ◽  
Author(s):  
B. P. deBoisblanc ◽  
K. Meszaros ◽  
A. Burns ◽  
G. J. Bagby ◽  
S. Nelson ◽  
...  
Keyword(s):  
Glucose Oxidation ◽  
Mechanical Performance ◽  
Lactate Production ◽  
Diaphragm Muscle ◽  
Tetanic Stimulation ◽  
Lactate Oxidation ◽  
Diaphragmatic Fatigue ◽  
Tension Generation

We investigated the effect of dichloroacetate (DCA) on tension generation and carbohydrate metabolism of the rat diaphragm in vitro. Isolated diaphragms were placed in individual organ chambers and were hooked to force-displacement transducers. Net lactate production and glucose and lactate oxidation were measured in vitro. Diaphragmatic fatigue was precipitated by in vivo endotoxemic shock, by in vitro hypoxia, or by in vitro repetitive tetanic stimulation. In diaphragms isolated from endotoxemic rats, DCA increased tension generation by 30 and 20% at stimulation frequencies of 20 and 100 Hz, respectively. Associated with changes in mechanical performance, DCA reduced net lactate production by 53% after 60 min of incubation and increased glucose oxidation 54% but had no effect on lactate oxidation. During in vitro hypoxia, DCA reduced net diaphragmatic lactate production by 30% and increased glucose oxidation by 45% but did not attenuate hypoxic fatigue. DCA had no effect on tension generation during repetitive tetanic stimulation. We conclude that DCA improves in vitro diaphragmatic fatigue due to endotoxicosis but not due to hypoxia or repetitive stimulation.

Sign in / Sign up

Export Citation Format

Share Document