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1.
Infect Dis Now ; 52(8S): S19-S20, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36108976

ABSTRACT

Reticence toward COVID-19 vaccination is more prevalent among women, people with low income, people who feel close to parties on the Far Right and Far Left and people who feel close to no party at all. It illustrates a mistrust of state institutions and policy-makers in general. The arguments in favor of Covid vaccine refusal are safety concern, and the contention that COVID is a mild disease. That said, vaccine hesitancy is vaccine-specific, with a major difference between Pfizer/Moderna and Oxford-AstraZeneca vaccines. Aside from vaccine hesitancy, vaccination intention rate has approached 80%.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Female , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination , Vaccination Refusal , Intention
2.
Infect Dis Now ; 51(5): 501-502, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34366088
3.
Public Health ; 194: 86-88, 2021 May.
Article in English | MEDLINE | ID: mdl-33866149

ABSTRACT

OBJECTIVES: Both the political appetite for a science-based coronavirus disease 2019 (COVID-19) policy and its acceptability to the public are little understood, at a time of sharp distrust not only of governments but also of scientists and their journals' review practices. We studied the case of France, where the independent Scientific Council on COVID-19 was appointed by President Macron on March 12, 2020. STUDY DESIGN: We conducted a survey on a representative sample of the French adult population. METHODS: Our data were collected by the French Institute of Public Opinion using a self-administered online questionnaire. This was completed by a sample of 1016 people stratified to match French official census statistics for gender, age, occupation, and so on. We conducted statistical analysis using Python (Pandas-SciPy-Statsmodels) with Chi-squared and Wilcoxon rank-sum tests to control for statistical significance. RESULTS: Intense media coverage has given the council a very high public profile, with three respondents out of four (73%) having heard about it. Perceptions are positive but complex. French citizens expect science to be important in political decision-making. Four of five (81.5%) want political decisions, in general, to be based on scientific knowledge. But one in two (55%) says that the government has not relied enough on science and only 36% are satisfied with the government's crisis management to date. Although most feel that the council has a legitimate advisory role even in situations of uncertainty (only 15% disagree), it is not perceived as fully independent. Only 44% think that it directly represents the scientific community, and only one of three people considers it completely independent from the government (39%) and the pharmaceutical industry (36%). CONCLUSIONS: Our study confirms that while the transparency of scientific advice is important, it alone cannot ensure public confidence in political decision-making. We suggest that efforts made today to instill a 'science-savvy' public culture-one that allows the complex articulation between scientific knowledge, uncertainty, and political decision-making to be understood and accounted for would greatly benefit evidence-based policy in future crises.


Subject(s)
COVID-19/prevention & control , Public Opinion , Public Policy , Science , Adult , COVID-19/epidemiology , Communications Media , Female , France/epidemiology , Government , Humans , Male , Surveys and Questionnaires
4.
Tree Physiol ; 22(5): 339-46, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11960758

ABSTRACT

Understanding the responses of riparian trees to water availability is critical for predicting the effects of changes in precipitation on riparian ecosystems. Dioecious Acer negundo L. (box elder) is a common riparian tree that is highly sensitive to water stress. Earlier studies indicated that the genders of A. negundo respond differently to water availability, with males being more conservative in their water use than females. To assess the potential effects of changes in precipitation on the sex ratio of riparian trees, we extended earlier studies of A. negundo by analyzing responses of male and female genotypes to interannual differences in water availability in a common garden. We measured growth of tree rings and used stable carbon isotope analysis of tree ring alpha-cellulose to integrate physiological responses to annual water treatments. During dry years, male and female trees exhibited similar growth and physiological responses. However, during wet years, females exhibited higher growth rates and lower carbon isotope ratios (indicating less conservative water use) than did males. Furthermore, we found that male trees exhibited similar stomatal behavior (inferred from integrated carbon isotope ratios) whether years were wet or dry, whereas females did not exhibit a consistent response to changes in water availability. We predict that with increasing precipitation and soil water availability, the representation of females will be favored because of shifts in the competitive interactions of the genders. Such changes may affect the reproductive output of these riparian trees and may influence overall water flux from riparian ecosystems. In addition, this study demonstrates the utility of carbon isotope analysis for assessing long-term responses of tree populations to shifts in water availability.


Subject(s)
Acer/physiology , Cellulose/analysis , Trees/physiology , Acer/chemistry , Acer/growth & development , Dehydration , Ecosystem , Rain , Sex Factors , Trees/chemistry , Trees/growth & development , Utah , Wood
5.
Oecologia ; 123(3): 330-341, 2000 May.
Article in English | MEDLINE | ID: mdl-28308587

ABSTRACT

Atmospheric CO2 partial pressure (pCO2) was as low as 18 Pa during the Pleistocene and is projected to increase from 36 to 70 Pa CO2 before the end of the 21st century. High pCO2 often increases the growth and reproduction of C3 annuals, whereas low pCO2 decreases growth and may reduce or prevent reproduction. Previous predictions regarding the effects of high and low pCO2 on C3 plants have rarely considered the effects of evolution. Knowledge of the potential for evolution of C3 plants in response to CO2 is important for predicting the degree to which plants may sequester atmospheric CO2 in the future, and for understanding how plants may have functioned in response to low pCO2 during the Pleistocene. Therefore, three studies using Arabidopsis thaliana as a model system for C3 annuals were conducted: (1) a selection experiment to measure responses to selection for high seed number (a major component of fitness) at Pleistocene (20 Pa) and future (70 Pa) pCO2 and to determine changes in development rate and biomass production during selection, (2) a growth experiment to determine if the effects of selection on final biomass were evident prior to reproduction, and (3) a reciprocal transplant experiment to test if pCO2 was a selective agent on Arabidopsis. Arabidopsis showed significant positive responses to selection for high seed number at both 20 and 70 Pa CO2 during the selection process. Furthermore, plants selected at 20 Pa CO2 performed better than plants selected at 70 Pa CO2 under low CO2 conditions, indicating that low CO2 acted as a selective agent on these annuals. However, plants selected at 70 Pa CO2 did not have significantly higher seed production than plants selected at 20 Pa CO2 when grown at high pCO2. Nevertheless, there was some evidence that high CO2 may also be a selective agent because changes in development rate and biomass production during selection occurred in opposite directions at low and high pCO2. Plants selected at high pCO2 showed no change or reductions in biomass relative to control plants due to a decrease in the length of the life cycle, as indicated by earlier initiation of flowering and senescence. In contrast, selection at low CO2 resulted in an average 35% increase in biomass production, due to an increase in the length of the life cycle that resulted in a longer period for biomass accumulation before senescence. From the Arabidopsis model system we conclude that some C3 annuals may have produced greater biomass in response to low pCO2 during the Pleistocene relative to what has been predicted from studies exposing a single generation of C3 plants to low pCO2. Furthermore, C3 annuals may exhibit evolutionary responses to high pCO2 in the future that may result in developmental changes, but these are unlikely to increase biomass production. This series of studies shows that CO2 may potentially act as a selective agent on C3 annuals, producing changes in development rate and carbon accumulation that could not have been predicted from single-generation studies.

6.
Br J Clin Pharmacol ; 49(1): 15-22, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10606833

ABSTRACT

Aims To establish whether enantioselective metabolism of racemic (rac )-salbutamol occurs in the lungs by determining its enantiomeric disposition following inhalation, in the absence and presence of oral charcoal, compared with that following the oral and intravenous routes. Methods Fifteen healthy subjects (eight male) were randomized into an open design, crossover study. Plasma and urine salbutamol enantiomer concentrations were measured for 24 h following oral (2 mg) with or without oral charcoal (to block oral absorption), inhaled (MDI; 1200 microg) with or without oral charcoal and intravenous (500 microg) rac-salbutamol. Systemic exposure (plasma AUC(0,infinity) and urinary excretion (Au24h ) of both enantiomers were calculated, and relative exposure to (R)-salbutamol both in plasma (AUC(R)-/AUC(S)- ) and urine (Au(R)-/Au(S)- ) was derived for each route. Relative exposure after the inhaled with charcoal and oral routes were compared with the intravenous route. Results AUC(R)-/AUC(S)- [geometric mean (95% CI)] was similar following the intravenous [0.32 (0.28, 0.36)] and inhaled with charcoal rates [0.29 (0.24, 0.36); P=0.046], but was far lower following oral dosing [0.05 (0.03, 0.07); P<0.001]. Similar results were found when relative exposure was analysed using Au24h. Conclusions These results show no evidence of significant enantioselective presystemic metabolism in the lungs, whilst confirming it in the gut and systemic circulation, indicating that the (R)- and (S)-enantiomers are present in similar quantities in the airways following inhaled rac-salbutamol.


Subject(s)
Albuterol/pharmacokinetics , Bronchodilator Agents/pharmacokinetics , Lung/metabolism , Administration, Inhalation , Administration, Oral , Adult , Albuterol/administration & dosage , Albuterol/chemistry , Antidotes/pharmacology , Area Under Curve , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/chemistry , Charcoal/pharmacology , Cross-Over Studies , Female , Half-Life , Humans , Injections, Intravenous , Male , Stereoisomerism
7.
Am J Respir Cell Mol Biol ; 13(2): 175-84, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7542897

ABSTRACT

We compared inhibitory nonadrenergic noncholinergic (i-NANC) neural relaxations, evoked by electrical field stimulation (EFS), at three levels (main [MA], proximal [PA], and distal [DA] airways) of isolated human airways and correlated these with nitric oxide synthase-immunoreactive (NOS-IR) nerves, using antiserum raised to rat cerebellar NOS. Maximal relaxations to papaverine (100 microM) were reduced in PA and DA (MA: 1,712 +/- 219 mg, n = 12; DA: 862 +/- 69 mg, n = 5, P < 0.05 versus MA); hence, subsequent relaxations were expressed as a percentage of the papaverine maximum. EFS elicited frequency-dependent relaxations that were largest in MA and reduced in PA and DA, especially at high stimulation frequencies (10 Hz EFS: MA: 51.6 +/- 3.7%, n = 12; PA: 30.5 +/- 6.0%, n = 6, P < 0.01 versus MA; DA: 17.8 +/- 3.6%, n = 5, P < 0.001 versus MA). The NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME) (100 microM) and tetrodotoxin (3 microM) significantly inhibited i-NANC responses at all frequencies, leaving an L-NAME-resistant non-neural relaxation at frequencies > 5 Hz which was reduced in PA and DA. Cumulative concentration-response studies to sodium nitroprusside (1 nM to 0.1 mM) and the NO donor 3-morpholinosydnonimine (1 nM to 1 mM) were not significantly different in PA and DA, suggesting impaired relaxation is not caused by impaired guanylyl cyclase activity. Total nerve density, shown by protein gene product 9.5 staining, was not significantly different in PA and DA; however, NOS-IR nerve density was reduced in PA and DA (NOS-IR [intercepts/mm2]: MA: 705 +/- 98, n = 6; DA: 284 +/- 32, n = 6, P < 0.01 versus MA). These studies demonstrate that i NANC neural relaxations are reduced in DA, apparently due to a decrease in the density of nitrergic innervation.


Subject(s)
Bronchi/innervation , Bronchoconstriction/physiology , Nitric Oxide/immunology , Trachea/innervation , Adolescent , Adult , Amino Acid Oxidoreductases/antagonists & inhibitors , Arginine/analogs & derivatives , Arginine/pharmacology , Autonomic Nervous System/physiology , Bronchi/chemistry , Bronchi/physiology , Child , Electrophysiology , Female , Humans , Male , Middle Aged , Molsidomine/analogs & derivatives , Molsidomine/pharmacology , Muscle, Smooth/innervation , NG-Nitroarginine Methyl Ester , Neural Inhibition/physiology , Nitric Oxide/analysis , Nitric Oxide/biosynthesis , Nitric Oxide Synthase , Nitroprusside/pharmacology , Papaverine/pharmacology , Tetrodotoxin/pharmacology , Trachea/chemistry , Trachea/physiology , Vasodilator Agents/pharmacology
8.
Am J Respir Crit Care Med ; 152(1): 377-80, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7599849

ABSTRACT

5-hydroxytryptamine (5-HT) may not play a major role in controlling human airway smooth muscle tone, as it has little direct effect on airway caliber. However, its role as a neuromodulator has not been determined. We have identified a facilitatory effect of 5-HT on cholinergic neurotransmission and characterized the 5-HT receptors involved in human and guinea pig trachea. In guinea pig trachea, 5-HT facilitated electric field stimulation-induced cholinergic bronchoconstriction in a concentration-dependent manner (EC50 = 2.6 microM). The 5-HT3/4 and 5-HT3 antagonists, ICS 205-930 and ondansetron, inhibited the effect of 5-HT competitively (pA2 values of 7.3 and 7.1, respectively); methiothepin (5-HT1/2C antagonist), ketanserin (5-HT2A antagonist), and GR 113808A (5-HT4 antagonist) had no effect. The rank order of potency of 5-HT agonists was 5-HT > 2-methyl-5-HT (5-HT3 selective) > 5-methoxytryptamine (5-HT4 selective) > alpha-methyl-5-HT (5-HT2 selective). 5-carboxamidotryptamine (5-HT1A/B/D) and sumatriptan (5-HT1D selective) were essentially inactive. 5-Hydroxytryptamine had no effect on contractile responses to exogenous acetylcholine, suggesting that 5-HT facilitates cholinergic bronchoconstriction via prejunctional receptors. In human bronchi, 5-HT also facilitated cholinergic bronchoconstriction, which was inhibited by ICS 205-930. The effects of the 5-HT3 antagonists and selective agonists in human and guinea pig airways suggests that these facilitatory effects are mediated by 5-HT3 receptors.


Subject(s)
Bronchoconstriction/physiology , Neurotransmitter Agents/physiology , Receptors, Serotonin/physiology , Serotonin/physiology , Adult , Animals , Bronchi/innervation , Electric Stimulation , Female , Guinea Pigs , Humans , Male , Receptors, Serotonin/classification , Receptors, Serotonin/drug effects , Serotonin/pharmacology , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Synaptic Transmission/physiology , Trachea/innervation
9.
J Physiol ; 483 ( Pt 2): 525-36, 1995 Mar 01.
Article in English | MEDLINE | ID: mdl-7650619

ABSTRACT

1. We have investigated the correlation between relaxation and changes in cyclic nucleotide content of human tracheal smooth muscle (HTSM) in vitro following inhibitory non-adrenergic non-cholinergic (i-NANC) neural bronchodilator responses evoked by electrical field stimulation (EFS), and compared these with changes seen with sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1) and vasoactive intestinal peptide (VIP). The effects of N omega-nitro-L-arginine methyl ester (L-NAME), Methylene Blue and alpha-chymotrypsin (alpha-CT) were studied. 2. EFS (10 Hz, 1 ms, 40 V for 30 s) evoked a time-dependent relaxation accompanied by a concurrent rise in cGMP, both of which were maximal at 30 s and unaffected by epithelium removal. Levels of cAMP were more variable than those of cGMP and were not significantly changed at any time point. 3. SIN-1 (1 mM) and SNP (100 microM) also produced time-dependent relaxations which were maximal between 2 and 8 min, accompanied by concomitant rises in cGMP; however, these changes were larger than those associated with i-NANC relaxations. cAMP levels were unchanged at all time points. 4. EFS-evoked i-NANC relaxations and cGMP increases (time, t = 30 s) were inhibited by L-NAME. The effects were partially reversed by L-arginine (1 mM), but not by D-arginine. D-NAME and alpha-CT (2 u ml-1) had no effect on either relaxation or cGMP accumulation. Tetrodotoxin (TTX, 3 microM) inhibited both relaxation and cGMP accumulation. 5. VIP (1 microM) also produced a time-dependent relaxation associated with a concurrent rise in cAMP levels with no change in cGMP levels. 6. Methylene Blue (10 microM) partially inhibited EFS (10 Hz)-evoked i-NANC relaxation and cGMP accumulation, and almost completely inhibited both relaxation and cGMP accumulation evoked by SIN-1 (1 mM). Methylene Blue had no significant effect on relaxation or cGMP accumulation evoked by SNP (100 microM). 7. Neural i-NANC relaxations in HTSM are associated with a concurrent selective accumulation of cGMP which is unaffected by epithelium removal. This is inhibited in a stereoselective manner by L-NAME and mimicked by SNP and SIN-1; however, cGMP accumulation was greatly increased with SNP and SIN-1 suggesting compartmentalized changes in cGMP content. VIP also caused relaxation associated with an increase of cAMP; however, no evidence was found for VIP being involved in i-NANC relaxation. Hence nitric oxide (NO), or a NO-containing complex, appears to mediate i-NANC responses in human trachea in vitro.


Subject(s)
Bronchoconstriction/physiology , Cyclic GMP/physiology , Trachea/innervation , Adenosine Monophosphate/metabolism , Adolescent , Adult , Arginine/analogs & derivatives , Arginine/pharmacology , Child , Chymotrypsin/pharmacology , Electric Conductivity , Epithelium/physiology , Female , Humans , Male , Methylene Blue/pharmacology , Middle Aged , Molsidomine/analogs & derivatives , Molsidomine/pharmacology , Muscle, Smooth/physiology , NG-Nitroarginine Methyl Ester , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Nitroprusside/pharmacology , Tetrodotoxin/pharmacology , Time Factors , Vasoactive Intestinal Peptide/pharmacology , Vasodilator Agents/pharmacology
10.
Arch Int Pharmacodyn Ther ; 329(1): 97-110, 1995.
Article in English | MEDLINE | ID: mdl-7639623

ABSTRACT

Human airway smooth muscle possesses a prominent nonadrenergic noncholinergic (i-NANC) bronchodilator response. Nitric oxide (NO) appears to account for all the i-NANC response in human central and peripheral airways in vitro. Furthermore, it appears that i-NANC relaxations in human trachea are associated with a concomitant selective elevation of cGMP, but not cAMP levels, which are inhibited by an NO synthase (NOS) inhibitor. This confirms the hypothesis that the L-arginine/NO/cGMP pathway is responsible for mediating the i-NANC response in this tissue. It is not certain from where the NO is formed or the location of the NOS enzyme. However, in human trachea, NOS immunoreactivity (NOS-IR) has been described in nerve fibres originating from intrinsic neurons. In addition, the density of NOS-IR is reduced from proximal to distal airways and this correlates with functional data describing a reduced i-NANC relaxation response from central to peripheral airways. The i-NANC bronchodilator nerves are the only neural relaxant pathway in human airways and, therefore, it is important to determine whether there is any defect in the ability of these nerves to function in diseased airways. In fact, functional and immunohistochemical data suggest that there may be a deficiency in NOS-IR nerves leading to a decreased i-NANC response in tissue from patients with cystic fibrosis. NOS inhibitors appear to enhance the cholinergic bronchoconstriction in human airways in vitro. Therefore, if the nitrergic innervation is dysfunctional in inflammatory conditions, its absence may lead to exaggerated bronchoconstriction.


Subject(s)
Neurotransmitter Agents/physiology , Nitric Oxide/physiology , Respiratory Physiological Phenomena , Arginine/analogs & derivatives , Arginine/pharmacology , Bronchoconstriction/physiology , Bronchodilator Agents/pharmacology , Humans , Muscle, Smooth/physiology , NG-Nitroarginine Methyl Ester , Nitric Oxide/antagonists & inhibitors , Respiration/drug effects , Respiration/physiology , Respiratory System/drug effects
11.
Am J Respir Crit Care Med ; 150(6 Pt 1): 1640-5, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7952627

ABSTRACT

We investigated the effect of Ba 679 BR, a novel long-acting antimuscarinic agent, on cholinergic neural responses in guinea pig and human airways. Ba 679 BR, atropine, and ipratropium bromide inhibited electrical field stimulation (EFS)-induced contraction with IC50 values of 0.17, 0.74, and 0.58 nM, respectively, in guinea pig trachea. Ba 679 BR had a slower onset and longer duration of action than atropine or ipratropium bromide (the times required to attain 50% of the maximum response were 34.8, 3.8, and 7.6 min, respectively, and the times required for 50% recovery of the response were 540, 31.6, and 81.2 min, respectively). Ba 679 BR, as well as atropine and ipratropium bromide, facilitated evoked [3H]acetylcholine release (an inhibitory effect on prejunctional muscarinic M2 receptors). The facilitation of acetylcholine release by Ba 679 BR was lost 2 h after washout, however, when there was still complete blockade of cholinergic contractile responses evoked by EFS (an effect on airway smooth muscle M3 receptors), confirming binding studies that suggest that Ba 679 BR shows "kinetic receptor subtype selectivity" for M3 over M2 receptors. The high potency, slow onset, and long duration of action of Ba 679 BR were also observed in human bronchi, suggesting that Ba 679 BR may be a useful drug to provide convenient therapy for patients with obstructive airway disease.


Subject(s)
Bronchodilator Agents/pharmacology , Cholinergic Antagonists/pharmacology , Cholinergic Fibers/drug effects , Scopolamine Derivatives/pharmacology , Synaptic Transmission/drug effects , Trachea/drug effects , Acetylcholine/metabolism , Animals , Bronchi/drug effects , Bronchi/innervation , Cholinergic Fibers/physiology , Guinea Pigs , Humans , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/innervation , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/physiology , Time Factors , Tiotropium Bromide , Trachea/innervation
12.
Br J Pharmacol ; 111(4): 1095-102, 1994 Apr.
Article in English | MEDLINE | ID: mdl-7518294

ABSTRACT

1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM) produced a concentration-dependent inhibition of the excitatory NANC response with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM) when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by unpaired t tests; however, this concentration appeared to produce a leftward shift (approximately 10 fold) of the 5-HT concentration-inhibition curve. Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by activation of 5-HT2A receptors on airway smooth muscle. In the presence of ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100 microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1 microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5-HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205-930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5-HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM. 5. Selective 5-HT receptor agonists were also tested on excitatory NANC responses. 5-Carboxamidotryptamine (5-CT, 0.1-100 MicroM) was the most potent, producing a concentration-dependent inhibition with an EC50 of 0.13 MicroM. Calculation of approximate IC25 values (concentration of the agonist required to give a 25% inhibition of the excitatory NANC response) gave a rank order of potency 5-CT > 5-HT> > 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) >alpha-methyl-5-hydroxytryptamine (alpha-Me-5HT). Sumatriptan, 5-methoxytryptamine (5-MeOT) and 2-methyl-5-hydroxytryptamine (2-Me-5HT) were essentially inactive with IC25> 100 MicroM.6. 5-HT (10 microM) did not significantly affect contractile responses to exogenously applied substance P(1 nM-10 Microm).7. The effect of 5-HT was unchanged after incubation with the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 100 Microm). However, pretreatment with charybdotoxin (ChTX,0.1-30 nM), a blocker of the large conductance Ca2+-activated K+channel (K+ca), produced a concentration-dependent inhibition of the effect of 5-HT (10 MicroM).8. 5-HT evokes a concentration-dependent inhibition of e-NANC bronchoconstriction in guinea-pig isolated bronchi but does not affect cumulative concentration-dependent contractile responses to substance P, suggesting that inhibition is via a prejunctional receptor. Effects of selective antagonists and agonists suggest that an atypical 5-HT receptor mediates this inhibition. The inhibitory effect of 5-HT does not involve the production of NO, but may involve the opening a ChTX-sensitive K+ca channel.These data suggest that an atypical 5-HT receptor inhibits the release of neuropeptides from sensory C fibres and may act as other inhibitory neuromodulators via the opening of a common K'channel.


Subject(s)
Bronchi/innervation , Bronchoconstriction , Receptors, Serotonin/physiology , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Bronchoconstriction/drug effects , Charybdotoxin , Dose-Response Relationship, Drug , Guinea Pigs , In Vitro Techniques , Male , Methiothepin/pharmacology , NG-Nitroarginine Methyl Ester , Phentolamine/pharmacology , Scorpion Venoms/pharmacology , Substance P/pharmacology
13.
J Clin Invest ; 92(2): 736-42, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8349813

ABSTRACT

Human airway smooth muscle possesses an inhibitory nonadrenergic noncholinergic neural bronchodilator response mediated by nitric oxide (NO). In guinea pig trachea both endogenous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase alpha-chymotrypsin on contractile responses evoked by electrical field stimulation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in trachea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism of this modulation we then studied the effects of endogenous NO on acetylcholine (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism of ACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways.


Subject(s)
Acetylcholine/metabolism , Arginine/analogs & derivatives , Atropine/pharmacology , Bronchi/physiology , Muscle Contraction/drug effects , Muscle, Smooth/physiology , Nitric Oxide/metabolism , Trachea/physiology , Vasoactive Intestinal Peptide/pharmacology , Adolescent , Adult , Arginine/pharmacology , Bronchi/drug effects , Child , Child, Preschool , Choline/metabolism , Electric Stimulation , Female , Humans , In Vitro Techniques , Isomerism , Lung/innervation , Male , Middle Aged , Muscle, Smooth/drug effects , NG-Nitroarginine Methyl Ester , Tetrodotoxin/pharmacology , Trachea/drug effects , omega-N-Methylarginine
14.
Br J Clin Pharmacol ; 35(3): 318-20, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8471412

ABSTRACT

Bronchodilating effects of the novel potassium channel opener HOE 234 were examined in human bronchi in vitro and compared with those of BRL 38227. HOE 234 produced concentration-dependent relaxations of spontaneous tone and of tone increased by methacholine (10(-6) M), with mean EC50 values of 11 nM and 47 nM, respectively (n = 5). The relaxation produced by HOE 234 was 7 and 3.5 fold more potent than that by BRL 38227 on spontaneous and induced tone, respectively, and was inhibited by glibenclamide (10(-5) M). These results suggest that HOE 234 is a potent bronchodilator which activates ATP-sensitive potassium channels in human airways.


Subject(s)
Bronchi/drug effects , Bronchodilator Agents/pharmacology , Chromans/pharmacology , Muscle Relaxants, Central/pharmacology , Potassium Channels/drug effects , Pyrrolidines/pharmacology , Adenosine Triphosphate/metabolism , Adult , Benzopyrans/pharmacology , Bronchi/physiology , Cromakalim , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , Male , Middle Aged , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Pyrroles/pharmacology
15.
J Anim Sci ; 69(6): 2282-8, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1885348

ABSTRACT

Two gestating cow winter grazing trials and two lactating cow drylot trials were conducted to evaluate the use of a slowly degraded protein source in corn plant diets for mature beef cows. Gestating beef cows grazing cornstalks were supplemented with .86 kg/(cow.d) of a 20% crude protein equivalent (CPE) pellet (DM basis). In Trial 1 cows fed diets containing 80% dehydrated alfalfa meal (high DEHY) gained more weight (P less than .05) than those fed diets containing 40% dehydrated alfalfa meal (low DEHY) or urea but not more than the cows fed soybean meal (SBM); however, no differences among treatments were observed in Trial 2. Four lactation diets composed of ground corncobs and corn silage were supplemented with either urea, SBM, or two levels of dehydrated alfalfa meal (DEHY) as N sources. The same amount of supplemental N was fed in both trials, consisting of .31 kg of natural protein for the SBM and low DEHY treatments or .42 kg for high DEHY. Ammoniated corncobs replaced 35% of the ground corncobs in Trial 4. Diets were calculated to contain (DM basis) 55% TDN and 9% CPE in Trial 3 and 11% CPE in Trial 4. In Trial 3, lactating cows supplemented with DEHY gained more weight (P less than .10) than those fed the urea supplement but not more than those fed SBM. Gains by cows fed the urea- and SBM-supplemented diets were not different (P greater than .10). Cow weight gains in Trial 4 were not affected by type of protein supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Animal Feed , Cattle/growth & development , Dietary Proteins/metabolism , Lactation/physiology , Pregnancy, Animal/metabolism , Animals , Cattle/physiology , Female , Medicago sativa , Milk/chemistry , Milk/metabolism , Pregnancy , Urea/administration & dosage , Weight Gain , Zea mays
16.
J Anim Sci ; 69(6): 2289-93, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1885349

ABSTRACT

Two experiments, using Angus x Hereford spring-calving beef cows in mid- or late lactation nursing Simmental-sired calves, were conducted to evaluate the relative value of a corn gluten meal-blood meal mixture (CGM-BM; 50% of supplemental protein from each source). In Exp. 1 (78 d), cows in late lactation were assigned to one of three treatments: control at 8.2% CP (C), soybean meal at 10.4% CP (SBM), or CGM-BM at 10.3% CP. Diets were calculated to be isocaloric at 55% TDN. In Exp. 2 (65 d), cows in mid-lactation were assigned to four treatments: urea, SBM, low CGM-BM (LM), and high CGM-BM (HM). Diets in Exp. 2 were isonitrogenous (9.5% CP) and isocaloric (55% TDN). Diets in both experiments were based on ammoniated wheat straw and corn silage. Weight gains of cows and cow-calf pairs were greater (P less than .06) when protein was supplemented in Exp. 1. Gains were lower for cows fed urea (P less than .03) in Exp. 2 but were similar when cows were supplemented with SBM vs either the low or the high level of CGM-BM. Performance of calves did not differ among dietary treatments.


Subject(s)
Animal Feed , Cattle/growth & development , Dietary Proteins/metabolism , Lactation/physiology , Pregnancy, Animal/metabolism , Animals , Cattle/physiology , Dietary Proteins/administration & dosage , Female , Pregnancy , Silage , Glycine max , Triticum , Urea/administration & dosage , Weight Gain , Zea mays
17.
J Anim Sci ; 69(6): 2294-302, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1653191

ABSTRACT

Grazing trials were conducted utilizing individually supplemented lactating beef cows in a 2-yr study to determine the effect of supplemental escape protein (EP) on cow/calf performance during the active growth periods of smooth brome and big bluestem. Graded levels (0, .11, .23, and .34 kg of EP/animal from an equal-protein-basis mixture of blood meal and corn gluten meal were offered daily, replacing corn starch and molasses, which was used as the energy control. All cows received 582 g of supplemental DM/d. Analyses for the smooth brome study indicated a cubic response (P less than .05) to milk production and calf daily gain. No response to EP supplementation (P greater than .10) was observed for the big bluestem study. Analysis of esophageal extrusa samples collected throughout the grazing seasons for both years demonstrated that quality of forage selected by the animal decreased as the trial progressed. Using a 16-h modified dacron bag technique that did not adjust for microbial attachment, protein escaping degradation for smooth brome and big bluestem was estimated to range from 7.0 to 14.5% and 22.2 to 30.3%, respectively. There was limited response to a moderate level of EP supplementation of lactating cows grazing smooth brome, but calf gains were depressed by both the low and the high levels of EP. Lactating cows grazing big bluestem did not respond to EP supplementation, but added energy supplement depressed calf gains.


Subject(s)
Animal Feed , Animals, Suckling/growth & development , Cattle/physiology , Dietary Proteins/administration & dosage , Lactation/physiology , Animals , Cattle/growth & development , Dietary Fiber/metabolism , Energy Intake , Female , Molasses , Poaceae , Starch/administration & dosage , Weight Gain
18.
J Anim Sci ; 69(3): 917-22, 1991 Mar.
Article in English | MEDLINE | ID: mdl-2061261

ABSTRACT

Albendazole (methyl 5-propylthio-1 H-benzimidazol-2-yl carbamate) was used as an anthelmintic in a 3-yr study involving 578 beef cows and 438 nursing calves. Infection levels for nematodes, coccidia, and tapeworm were relatively low throughout the 3-yr period. Eggs per gram of feces in cows and calves were lower (P less than .01) 2 wk posttreatment but were not different 5 mo later, when calves were weaned. Cow weight gain, rate and time of conception, and adjusted calf weaning weights were not affected significantly by deworming of either cows or calves. Level of nematode infection measured as eggs per gram of feces was higher (P less than .01) in younger cows than in mature cows. Although deworming with Albendazole lowered (P less than .01) nematode infection levels, no responses were observed in cow or calf performance.


Subject(s)
Albendazole/therapeutic use , Cattle Diseases/drug therapy , Intestinal Diseases, Parasitic/veterinary , Age Factors , Animals , Cattle , Cattle Diseases/parasitology , Cestode Infections/drug therapy , Cestode Infections/parasitology , Cestode Infections/veterinary , Coccidiosis/drug therapy , Coccidiosis/parasitology , Coccidiosis/veterinary , Feces/parasitology , Female , Intestinal Diseases, Parasitic/drug therapy , Intestinal Diseases, Parasitic/parasitology , Nematode Infections/drug therapy , Nematode Infections/parasitology , Nematode Infections/veterinary , Parasite Egg Count/veterinary , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/parasitology , Pregnancy Complications, Infectious/veterinary , Seasons , Weight Gain
19.
J Anim Sci ; 67(6): 1418-24, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2768099

ABSTRACT

Animal selectivity and digestibility differences among switchgrass strains selected for different in vitro dry matter digestibilities (IVDMD) were measured in a grazing trial with esophageally fistulated steers and a sheep digestion trial. Extrusa selected by esophageally fistulated steers grazing high-IVDMD (Trailblazer), Pathfinder and low-IVDMD strains of switchgrass were compared, as were top and whole plant hand-clipped samples from each strain. Trailblazer extrusa had higher (P less than .1) in vitro organic matter disappearance (IVOMD) and lower (P less than .1) NDF and ADF than Pathfinder extrusa. Extrusa from all three strains appeared to be of higher quality than top or whole plant hand-clipped samples. In vitro organic matter disappearance tended to be highest for Trailblazer top hand-clipped samples. Composition of hand-clipped samples among strains was not significantly different. Mature crossbred wethers were used to compare Trailblazer and Pathfinder switchgrass hay in a digestion trial. No differences (P greater than .1) were detected between strains for DMI or apparent digestibility of DM, NDF, ADF and CP. Extrusa from Trailblazer switchgrass that had been selected for whole plant IVDMD had higher IVOMD; however, there was no indication that steers selected a differentially higher IVOMD for one strain than another.


Subject(s)
Animal Feed , Cattle/physiology , Digestion , Poaceae , Sheep/physiology , Animals , Feces/analysis , Food Preferences , Humans , Species Specificity
20.
J Anim Sci ; 63(4): 1054-62, 1986 Oct.
Article in English | MEDLINE | ID: mdl-3021702

ABSTRACT

Mefluidide, a plant growth regulator, was evaluated in two cow-calf grazing trials and one herbage trial on smooth brome (Bromus inermis) pastures stocked at recommended densities in eastern Nebraska. Mefluidide-treated pasture increased cow and calf production during August of 1982 (P = .03) and calf production was greater during July of 1983 (P = .09). Mefluidide-treated smooth brome pastures increased calf production over the 1982 grazing season (P = .11) and cow gain over the 1982 (P = .12) and 1983 grazing seasons (P = .13). Mefluidide decreased neutral detergent fiber (NDF) content and increased crude protein content of smooth brome during both years (P less than .05), and increased in vitro dry matter disappearance (IVDMD) in 1982 (P less than .05). In ungrazed smooth brome, mefluidide treatment appeared to shift dry matter production to green leaves from green stem and brown leaf and stem fractions. Cell wall components [NDF, acid detergent fiber (ADF) and lignin] of green leaves were not affected significantly by mefluidide treatment, although green stems treated with mefluidide were lower in ADF and lignin (P less than .05).


Subject(s)
Acetamides/pharmacology , Animal Feed , Cattle/physiology , Animals , Body Weight , Cattle/growth & development , Dietary Fiber , Poaceae , Seasons
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