Methacholine dose-response curves in normal and asthmatic man: Effect of starting conductance and pharmacological antagonism

1984 ◽  
Vol 66 (6) ◽  
pp. 665-673 ◽  
Author(s):  
K. F. Chung ◽  
P. D. Snashall
Keyword(s):  
Dose Response ◽  
Normal Subjects ◽  
Small Degree ◽  
Response Curves ◽  
Significant Difference ◽  
Positive Linear Correlation ◽  
Dose Response Curves ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Different Doses

1. The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (scaw) in a body plethysmograph. 2. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sCaw (pD35) and the steepest slope of the response were measured from each curve. 3. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other. 4. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects. 5. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD3s after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges. 6. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD3s and in mean steepest slope in both normal and asthmatic groups. 7. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when

The guinea pig tracheobronchial spiral strip: responses to selected agonists

1978 ◽  
Vol 56 (5) ◽  
pp. 823-827 ◽  
Author(s):  
C. J. Hanna ◽  
S. H. Roth
Keyword(s):  
Regression Analysis ◽  
Guinea Pig ◽  
Dose Response ◽  
Effective Concentration ◽  
Relative Order ◽  
Response Curves ◽  
Response Data ◽  
Significant Difference ◽  
Dose Dependent

The guinea pig tracheal spiral strip is a useful preparation for studying bronchoconstrictor and bronchodilator compounds. Employing a simple and rapid modification of this technique, experiments were performed in vitro to quantitate the effects of selected bronchospastic agents on guinea pig tracheobronchial smooth muscle. Three sections of the main airways were prepared from each animal: an upper tracheal, a lower tracheal, and a bronchial segment. The dose-dependent contractile responses of the three tissue segments were determined for carbachol, acetylcholine, histamine, 5-hydroxytryptamine, and bradykinin, Differences were observed amongst the agonists in magnitudes of contraction, effective concentration ranges, and slopes of dose–response curves. ED25, ED50, and ED75, values were calculated from regression analysis of dose–response data. The relative order for these agents to produce maximum contractions was found to be carbachol [Formula: see text] acetylcholine > histamine > 5-hydroxytryptamine > bradykinin. Furthermore, it was found that there was no significant difference between the three tissue segments in their responses to the various agonists.

Pentobarbital and contraction of vascular smooth muscle

1975 ◽  
Vol 229 (6) ◽  
pp. 1635-1640 ◽  
Author(s):  
BT Altura ◽  
BM Altura
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dose Response ◽  
Mechanical Activity ◽  
Response Curves ◽  
Aortic Smooth Muscle ◽  
Dose Response Curves ◽  
Portal Veins ◽  
The Right ◽  
Dose Dependent

This study, with isolated rat aortic strips and portal veins, was undertaken to : 1) study the effects, if any, of pentobarbital Na (PTB) (5 x 10(-5) to 2 X 10(-3) M) on reactivity to epinephrine, serotonin, and KCl; 2) determine whether certain concentrations of PTB induce direct actions on aortic strips and portal veins; and 3) gain some insight into how these effects are brought about. The results indicate that PTB can: a) inhibit development of spontaneous mechanical activity in these vessels in anesthetic concentrations; b) dose-dependently attenuate contractions induced by epinephrine, serotonin, and KC1; c) cause a noncompetitive type displacement of the dose response curves of these vasoactive agents; d) attenuate Ca2+- induced contractions of potassium-depolarized aortic strips and portal veins concomitant with a dose-dependent displacement of these dose-response curves to the right; and e) rapidly relax drug as well as Ca2+ -induced contractions of aortas and portal veins. In addition, the data indicate that rat portal venous smooth muscle is more sensitive to the inhibitory actions of PTB than rat aortic smooth muscle. Overall, these data suggest that concentrations of PTB used to induce surgical anesthesia can exert profound depressant effects on at least two different types of vascular smooth muscle that may be related to actions on movement and/or translocation of Ca2+.

Prostaglandin fevers in rats: regulated change in body temperature or change in regulated body temperature?

1989 ◽  
Vol 257 (4) ◽  
pp. R695-R699 ◽  
Author(s):  
J. D. Feng ◽  
M. Price ◽  
J. Cohen ◽  
E. Satinoff
Keyword(s):  
Body Temperature ◽  
Dose Response ◽  
Dark Cycle ◽  
Response Curves ◽  
Vehicle Injection ◽  
Dose Dependent Fashion ◽  
Dose Response Curves ◽  
Dose Dependent ◽  
Light Part

Experiments examining the effects of central injections of E-series prostaglandins (PGE) on body temperature have only been done in the light part of a light-dark cycle. The present experiments examined the characteristics of fevers in rats after intraventricular PGE2 injections in both light and dark in a 12:12 h photoperiod. In the light, the change in body temperature (Tb) after 0.5 microgram was not significantly different from the change after vehicle injection. After injection of PGE2 (1, 2, 4, and 8 micrograms), Tb rose in a dose-dependent fashion. Mean initial Tb in the light was 36.4-36.6 degrees C. Tb rose a mean of 1.5 degrees C after 1 microgram, 1.9 degrees C after 2 micrograms, 2.7 degrees C after 4 micrograms, and 3.5 degrees C after 8 micrograms PGE2. A dose of 16 micrograms gave almost identical results as 8 micrograms. In the dark, mean initial Tb was 37.4-37.7 degrees C. Tb rose less than 0.8, 1.1, 1.4, and 2.3 degrees C after 1-8 micrograms PGE2, respectively. Thus there were two distinct dose-response curves for day and night. Nevertheless, peak Tb values attained in the two conditions were not significantly different from each other at any given dose. These results show that a particular dose of PGE2 raises Tb to a particular level, largely independent of either the Tb at the time of the injection or the phase of the light-dark cycle. However, the change in Tb at any dose depends strongly on initial Tb. Therefore, we urge researchers in the pharmacology of thermoregulation to report initial and final Tb values as well as changes in Tb.

scholarly journals Myorelaxant Effect of Essential Oil of Rhizome of Alpinia calcarata Rosc. on Rat Duodenal Smooth Muscle

2007 ◽  
Vol 2 (7) ◽  
pp. 1934578X0700200 ◽  
Author(s):  
Siddharth Pandey ◽  
Om Prakash ◽  
Anjum Zafar ◽  
Subrata K. Hore ◽  
Anil K. Pant ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Essential Oil ◽  
Dose Response ◽  
Response Curves ◽  
Competitive Antagonist ◽  
Rat Duodenum ◽  
Dose Response Curves ◽  
The Right ◽  
Dose Dependent

Analysis of the essential oil from the rhizome of Alpinia calcarata Rosc. (ACREO) by a combination of GC and GC-MS revealed the presence of 1,8-cineole (42.2%), endo-fenchyl acetate (14.7%), camphene (7.6%), β-pinene (6.9%), α-terpineol (5.3%) and camphor (5.0%). Twenty-three compounds were identified in the oil. ACREO showed dose dependent myorelaxant activity in rat duodenum. The dose response curves of acetylcholine (ACh) and CaCl2 were shifted by ACREO to the right with increases in EC50 values and decreases in Vmax. These findings suggest that ACREO is a non-competitive antagonist of ACh and calcium.

Topiramate Inhibits Trigeminovascular Neurons in the Cat

Cephalalgia ◽  
2004 ◽  
Vol 24 (12) ◽  
pp. 1049-1056 ◽  
Author(s):  
RJ Storer ◽  
PJ Goadsby
Keyword(s):  
Cumulative Dose ◽  
Dose Response ◽  
Sensory Input ◽  
Superior Sagittal Sinus ◽  
Maximum Effect ◽  
Response Curves ◽  
Sagittal Sinus ◽  
Dose Dependent Fashion ◽  
Dose Response Curves ◽  
Dose Dependent

To facilitate understanding the action of antimigraine preventives the effect of topiramate on trigeminocervical activation in the cat was examined. Animals ( n = 7) were anaesthetized and physiologically monitored. The superior sagittal sinus (SSS) was stimulated to produce a model of trigeminovascular nociceptive activation. Cumulative dose-response curves were constructed for the effect of topiramate at doses of 3, 5, 10, 30 and 50 mg/kg on SSS-evoked firing of trigeminocervical neurons. Topiramate reduced SSS evoked firing in a dose-dependent fashion. The maximum effect was seen over 30 min for the cohort taken together. At 3 mg/kg firing was reduced by 36 ± 13% (mean ± SEM) after 15 min. At 5 and 50 mg/kg firing was reduced by 59 ± 6% and 65 ± 14%, respectively, after 30 min. Inhibition of the trigeminocervical complex directly, or neurons that modulate sensory input, are plausible mechanisms for the action of preventives in migraine.

Variability of airway responses to inhaled histamine in normal subjects

1979 ◽  
Vol 47 (1) ◽  
pp. 51-58 ◽  
Author(s):  
M. P. Habib ◽  
P. D. Pare ◽  
L. A. Engel
Keyword(s):  
Dose Response ◽  
Lung Volume ◽  
Normal Population ◽  
Normal Subjects ◽  
Beta Blockade ◽  
Forced Expiration ◽  
Response Curves ◽  
Double Blind ◽  
Dose Response Curves ◽  
Airway Responses

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.

scholarly journals Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After in vitro Irradiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Mamadou Soumboundou ◽  
Julien Dossou ◽  
Yossef Kalaga ◽  
Innocent Nkengurutse ◽  
Ibrahima Faye ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Dose Response ◽  
Genotoxic Stress ◽  
European Ancestry ◽  
Response Curves ◽  
Blood Samples ◽  
Dicentric Chromosomes ◽  
Significant Difference ◽  
Dose Response Curves

Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry.Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0–4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations.Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10–17), centric rings (p = 4.0310–14), and resulting double-strand-breaks (DSB) (p = 1.32 10–18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa.Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.

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