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At least 685 records · Page 38Linked to original sources
PubMed1988

Quantitative selected ion monitoring processing system: software and hardware for the automated collection and analysis of selected ion monitoring data acquired for use in pharmacokinetic studies.

The Quantitative Selected Ion Monitoring Processing System (QSIMPS) is a collection of software and hardware which was designed with the capacity to analyze 30,600 samples per year in support of pharmacokinetic studies. On a per sample basis, QSIMPS was designed to inject a sample into the GC, control the GC divert valve, collect selected ion monitoring data, identify the peaks for the drug and one metabolite and each compound's reference standard, fit the peaks to a relevant chromatographic model, calculate chromatographic features of merit, calculate the peak heights and ratio of the drug and its reference standard and the metabolite and its reference standard, and, using calibration data, convert the ratio to an amount of drug. On a per tray (batch) basis, QSIMPS was designed to fit all the peak height ratios from the calibration standards to either a linear equation, or a generalized nonlinear isotope dilution equation, report a statistical analysis of the fit, and, using aliquot factors, convert the measured amount of drug into concentrations. On a per project basis, QSIMPS prints reports summarizing statistical data on the calibration standards and the quality assurance samples, and prints reports presenting the concentration data as a function of, for examples, subject, drug treatment, time postdose, etc., along with other ancillary data such as subject sex, weight, species, etc. In addition, QSIMPS can fit the concentration data to a number of common pharmacokinetic model-derived equations, and report the resulting pharmacokinetic parameters along with a statistical comparison of the parameters.

Chromatography, Gas↗
PubMed2006

Incorporation of selective population transfer and homo-spin decoupling into selective one-dimensional experiments.

The incorporation of selective population transfer (SPT) and homo-spin decoupling (HSD) into selective one-dimensional (1D) experiments has been shown to be very useful in obtaining information on the elucidation of the structure of organic compounds. To demonstrate this, the determination of the relative configuration of the sugar moiety of Mi-saponins has been presented.

Carbohydrate Sequence↗
PubMed2004

Selective aerobic oxidation of hydroxy compounds catalyzed by photoactivated ruthenium-salen complexes (selective catalytic aerobic oxidation).

Selective oxidation of alcohols to the corresponding carbonyl compounds is one of the most fundamental reactions in organic synthesis. Traditional methods for this transformation generally rely on stoichiometric amount of oxidants represented by Cr(VI) or DMSO reagents, though their synthetic utility is encumbered by unpleasant waste materials. From ecological and atom-economic viewpoints, catalytic aerobic oxidation is much more advantageous because molecular oxygen is ubiquitous and the byproduct is basically non-toxic water or hydrogen peroxide. On the other hand, phenol derivatives undergo oxidative coupling, forming C-C or C-O bond, through radical intermediates coupled with an electron-transfer process. Molecular oxygen is also well known to serve as electron acceptor in this reaction. Thus, a variety of transition metal complexes have so far been examined for aerobic oxidations of alcohols and phenols, and high catalytic activities have been achieved in some cases. However, stereo- and chemo-selective aerobic oxidations are still limited in number and are of current interest. Presented in this paper is our recent studies on catalytic aerobic oxidations with photoactivated nitrosyl ruthenium-salen complexes, including asymmetric oxidation of secondary alcohols to ketones (kinetic resolution), enantioselective oxidative coupling of 2-naphthols to binaphthols and oxygen-radical bicyclization of 2,2'-dihydroxystilbene, chemoselective oxidation of primary alcohols to aldehydes and diols to lactols, and asymmetric desymmetrization of meso-diols to lactols.

Journal Article↗
PubMed2000

Effect of quipazine, a selective 5-HT3 agonist, on dietary self-selection of different macronutrient diets in male and female rats.

Macronutrient intakes, 2h and 12h, following administration of a selective 5-HT3 agonist, quipazine, N methyl, dimaleate (QUIPAZINE; 2.5, 5.0 and 7.5 mg/kg, i.p.) at dark onset were examined in three groups of adult male and female Wistar rats fed different sources of the three macronutrients: Group 1 (casein, corn starch, safflower oil), Group 2 (egg protein, corn starch/sucrose, lard) and Group S (casein hydrolysate, maltose dextrin, butter). QUIPAZINE decreased total food intake only in female rats from Group 1 (2 h) at a dose of 7.5 mg/kg and Group 2 (2h and 12h) with doses of 2.5 and 7.5 mg/kg. Intakes from corn starch and corn starch/sucrose diet (12h) were reduced in male and female rats, respectively, with doses of 2.5 and 7.5 mg/kg of QUIPAZINE. In conclusion, when provided with different sources of the three macronutrients, quipazine injection reduces specifically carbohydrate ingestion from corn starch-containing diets in male and female rats. Thus, the nature of the macronutrient source is of major importance to assess the effect of a drug on nutrient-specific selection.

Analysis of Variance↗
PubMed1994

Comparison of the effect of inhaled selective and non-selective adrenergic agonists on cardiorespiratory parameters in chronic stable asthma.

Increased hypoxia has been found after beta 2 adrenoceptor agonists (but not adrenaline) in asthmatics. Combined with hypokalaemia and sympathomimetic stimulation, this may predispose to cardiac arrhythmias. We have compared the effects of nebulized adrenaline and a selective beta 2 agonist (salbutamol) on the arterial oxygen saturation (SaO2), minute ventilation (VE), forced expiratory volume in 1 s (FEV1), plasma potassium and the electrocardiogram (ECG) in patients with chronic stable asthma. Six patients were studied according to a randomized, placebo-controlled, double-blind cross-over protocol. Adrenaline (5 mg), salbutamol (5 mg) and placebo were administered during 4 min tidal breathing using a nebulizer driven by air. There was a fall in SaO2 after both adrenaline (mean % fall (SEM) 3.3 (0.2)) and salbutamol (4.0 (0.7)) associated with an increase in FEV1, with no change in VE. Therefore, the fall in SaO2 must have been caused by increased ventilation-perfusion imbalance. There was an increased heart rate after both adrenaline and salbutamol and ventricular ectopic beats and a short run of parasystole were recorded on the ECG in one patient after adrenaline and in two patients after salbutamol. No change was found in plasma potassium levels. We conclude that both adrenaline and a selective beta 2 agonist salbutamol can cause a fall in SaO2 and ventricular ectopy in some asthmatic patients.

Administration, Inhalation↗
PubMed1994

In favor of the selective model of positive selection.

The mechanisms of thymocyte commitment towards the CD4+ and CD8+ lineage remain unresolved. Two models--one based on instruction, the other on selection--have previously been proposed. The instructional model has been popularly received based on results of earlier studies. However, our data from MHC class II, class I, and double-deficient mice suggest otherwise. There exists a significant population of CD4+ cells that is intermediate in maturity between CD4+ CD8+ and fully mature CD4+ CD8- thymocytes in class II-deficient animals; an analogous population of CD4-CD8+ cells exists in class I-negative mice. We suggest that a selective model in which two TCR-MHC molecule engagements are required: the first induces a random down-modulation of either CD4 or CD8 and some differentiation; the second, involving the participation of the appropriate coreceptor, permits end-stage differentiation.

Animals↗
PubMed2001

Synergistic teratogenic effects induced by retinoids in mice by coadministration of a RARalpha- or RARgamma-selective agonist with a RXR-selective agonist.

To study the interaction of retinoid-induced limb defects and cleft palate on day 11 of gestation, a RXR-selective agonist (AGN191701, an arylpropenyl-thiophene-carboxylic acid derivative, 20 mg/kg orally) was coadministered with a RARalpha-agonist (Am580, an arylcarboxamidobenzoic acid derivative, 5 mg/kg orally) to NMRI mice. AGN191701 was neither fetotoxic nor teratogenic at the dose used but potentiated Am580-induced limb defects and cleft palate and prevented Am580-induced fetal weight retardation. These results suggest that Am580-induced limb defects and probably cleft palate on day 11 of gestation may be mediated via RARalpha-RXR heterodimerization, particularly in the absence of toxicokinetic interactions. AGN191701 was also coadministered with a RARgamma-agonist (CD437, an adamantyl-hydroxyphenyl naphthoic acid derivative, 15 mg/kg orally) on days 8 and 11 of gestation to investigate which CD437-induced defects are mediated via RARgamma-RXR heterodimerization. On day 8 of gestation, AGN191701 potentiated CD437-induced embryolethality, exencephaly, spina bifida aperta, cleft palate, and tail defects, as well as visceral and skeletal defects, but not micrognathia. On day 11 of gestation, the incidence of CD437-induced cleft palate and limb defects was also potentiated when coadministered with the RXR agonist. These results suggest that synergistic teratogenic effects can be induced by coadministration of two receptor-selective retinoids, indicating the importance of RARalpha-RXR and RARgamma-RXR heterodimers in producing structural defects during organogenesis.

Abnormalities, Drug-Induced↗
PubMed2006

Positive selective brain cooling method: a novel, simple, and selective nasopharyngeal brain cooling method.

Brain damage is worsened by hyperthermia and prevented by hypothermia. Conventional hypothermia is a non-selective brain cooling method that employs cooling blankets to achieve surface cooling. This complicated method sometimes induces unfavorable systemic complications. We have developed a positive selective brain cooling (PSBC) method to control brain temperature quickly and safely following brain injury. Brain temperature was measured in patients with a ventriculostomy CAMINO catheter. A Foley balloon catheter was inserted to direct chilled air (8 to 12 L/min) into each side of the nasal cavity. The chilled air was exhaled through the oral cavity. In most patients, PSBC maintained normal brain temperature. This new technique provides quick induction of brain temperature control and does not require special facilities.

Adult↗
PubMed1988

Loss of selectivity of so-called selective alpha 1-adrenoceptor agonists after phenoxybenzamine.

This study examined the nature of alpha-adrenoceptor subtype involved in pressor responses to so-called selective alpha 1-adrenoceptor agonists after treatment with phenoxybenzamine in vivo. The influence of prazosin (0.1 mg/kg) and of yohimbine (1 mg/kg) on the dose-response curves for cirazoline in the pithed rat, and for phenylephrine in the anaesthetized dog were compared, after various doses of phenoxybenzamine. In the pithed rat, after 0.05 mg/kg phenoxybenzamine, prazosin caused a displacement of the dose-response curve of cirazoline to the right which was much larger than that caused by yohimbine; after 0.3 mg/kg phenoxybenzamine, prazosin and yohimbine caused about equal displacements; after 1 mg/kg phenoxybenzamine, yohimbine caused a marked displacement, while prazosin was without effect. In the anaesthetized dog, after 1 mg/kg phenoxybenzamine, prazosin and yohimbine produced about equal rightward shifts of the dose-response curve for phenylephrine. However, after 3 mg/kg phenoxybenzamine the rightward shift of the dose-response curve for phenylephrine was much larger after yohimbine than after prazosin. In the anaesthetized dog, verapamil (1 mg/kg) caused a small and parallel rightward shift of the dose-response curve for phenylephrine before phenoxybenzmine and a large and nonparallel one after phenoxybenzamine (3 mg/kg); the effect of verapamil on responses to the selective alpha 2-adrenoceptor agonist UK-14,304 (before and after phenoxybenzamine) were similar to those on responses to phenylephrine after phenoxybenzamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1978

Properties of length-selective and non-length-selective adaptation mechanisms in human vision.

The contrast threshold elevation effect has been measured for one dimensional (grating) and for two dimensional (spot) stimulus patterns. It has been shown previously (Burton and Ruddock, 1978) that such stimuli elicit, respectively, non-length-selective and length-selective adaptation effects. It is established that, unlike the frequency shift effect, the contrast threshold elevation effect is sensitive to the width of the light but not to that of the dark elements of the stimulus patterns. Adaptation to spot patterns elicits a significant threshold elevation for detection of both spot and grating test stimuli, but only under monoptic viewing conditions. The experimental findings are summarized in a block-diagram and it is shown that adaptation to grating patterns is successfully described by the spatial frequency response data given by Maudarbocus and Ruddock (1973).

Adaptation, Physiological↗
PubMed1987

Exercise capacity, energy metabolism, and beta-adrenoceptor blockade. Comparison between a beta 1-selective and a non-selective beta blocker.

The effects of beta 1 and beta 1/2 blockade on exercise capacity were studied in 9 healthy normotensive subjects. Progressive maximal bicycle ergometer tests, followed by an endurance test at 80% of maximal work load, were performed during randomized, double-blind 3 day treatment periods with placebo, atenolol (beta 1) and oxprenolol (beta 1/2). The reduction of maximal work capacity (ca. 10%) was similar with atenolol and oxprenolol, despite a more pronounced maximal heart rate reduction with atenolol (from 175 +/- 2 to 132 +/- 3 beats.min-1) than with oxprenolol (to 138 +/- 2 beats.min-1). Exercise time during the endurance test was reduced from 36 +/- 4 min with placebo to 27 +/- 3 min with atenolol (p less than 0.05) and 24 +/- 3 min with oxprenolol (p less than 0.01) (atenolol vs. oxprenolol: p less than 0.05). During the endurance test, plasma glycerol and non-esterified fatty acid concentrations were reduced with both atenolol and oxprenolol. The glycerol reduction was more pronounced with oxprenolol than with atenolol, plasma NEFA concentrations being similar. Plasma glucose and lactate concentrations were reduced by oxprenolol but not with atenolol. These data show that submaximal exercise capacity at work loads representing similar relative exercise intensities is reduced during non-selective and beta 1-selective beta blockade. This reduction may be related to the effects of beta 1 blockade on energy metabolism, with possibly an additional effect of beta 2 blockade.

Adrenergic beta-Antagonists↗
PubMed1996

Cooperative selection of movements: the optimal selection model.

How one selects a movement when faced with alternative ways of doing a task is a central problem in human motor control. Moving the fingertip a short distance can be achieved with any of an infinite number of combinations of knuckle, wrist, elbow, shoulder, and hip movements. The question therefore arises: how is a unique combination chosen? In our model, choice is achieved by consideration of the similarity between the task requirements and the optimal biomechanical performance of each limb segment. Two variants of the model account for the movements that are selected when subjects freely oscillate the fingertip and when they tap against an obstacle. An important feature of both is that the impulse of collision with an obstacle (as in drumming with the hand or tapping with the finger) is assumed to be controlled in part by aiming for a point beyond the surface being struck. Thus, a force-related control variable may be represented and controlled spatially.

Arm↗
PubMed1988

Bias current modifies the selectivity of liquid membrane ion-selective microelectrodes.

A negative bias potential of up to -80 mV applied to the back of a liquid membrane ion-selective microelectrode containing classical "K+" ion-exchanger was found to make it more selective for millimolar concentrations of K+ over micromolar concentrations of choline, tetramethylammonium, tetraethylammonium and 5-hydroxytryptamine. Conversely, positive bias potential increased severalfold the sensitivity to micromolar concentrations of these ions while decreasing the sensitivity to K+. An increase in response amplitude for millimolar changes of ion concentration was also observed in neutral carrier electrodes for Na+, K+ and Ca2+ with negative bias potential. The various ions caused the resistances of the electrodes to change; these resistance changes contributed to the changes in response amplitude, but there were additional, unexplained, factors. The phenomenon was used to test if the signal from a K+ ion-exchanger microelectrode in extracellular space in bee retina was contaminated by substances other than K+.

Animals↗
PubMed1987

The effect of selective and non-selective cholinergic blockade on bombesin- and peptone-stimulated gastrin release.

We have studied the effects of the selective muscarinic M1-receptor antagonist pirenzepine and the non-selective muscarinic antagonist atropine on bombesin- and peptone-stimulated gastrin release in healthy subjects. Pirenzepine (i. v. bolus 0.6 mg/kg) and atropine (i. v. bolus 15 micrograms/kg, followed by an infusion of 5 micrograms.kg-1.h-1) were given in doses equipotent in terms of reduction of gastric acid secretion. Neither affected bombesin- or peptone-stimulated gastrin release. These findings do not support the involvement of M1-receptors in the cholinergic regulation of gastrin release and suggest that the reduction in acid secretion caused by pirenzepine is not mediated by inhibition of gastrin release.

Adult↗
PubMed1998

Asymmetric imine-ene reactions: diastereofacial selective reactions with chiral glyoxylate-derived alpha-imino esters and asymmetric catalysis of enantiofacial selective reactions with prochiral alpha-imino esters.

The diastereofacial selective "imine-ene" reactions with alpha-imino esters, prepared from (-)-8-phenylmenthyl glyoxylate, are shown to provide an efficient entry to the asymmetric synthesis of alpha-amino acids. The feasibility study of the asymmetric catalysis is also reported on the enantiofacial selective ene reactions with prochiral alpha-imino esters.

Amino Acids↗
PubMed1992

A comparison of the effects of the selective peripheral alpha 1-blocker terazosin with the selective beta 1-blocker atenolol on blood pressure, exercise performance and the lipid profile in mild-to-moderate essential hypertension.

The effects of six weeks of treatment with the selective peripheral alpha 1-adrenoceptor blocker terazosin, or the selective beta 1-adrenoceptor blocker atenolol on blood pressure, exercise performance and blood lipid profile were compared in a single-blind, randomized, crossover study of 17 patients with mild-to-moderate essential hypertension. Although both drugs significantly reduced blood pressure at rest, atenolol caused a larger fall in supine blood pressure (11/11 and 7.5/7.0 mmHg, atenolol and terazosin, respectively; p < 0.001). Both treatments controlled the pressor response to exercise, although a greater reduction in diastolic blood pressure was observed at the end of exercise on terazosin (74.0 +/- 5.7 and 91.6 +/- 4.0 mmHg, terazosin and atenolol, respectively; p < 0.01). Alpha 1-blocker therapy was not associated with any measurable improvement or deterioration in cardiopulmonary performance and exercise duration. Unlike atenolol, terazosin therapy had the potentially beneficial effect of reducing serum total cholesterol levels and increasing the high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol ratio.

Adult↗
PubMed1991

Response to selection for ethanol-induced locomotor activation: genetic analyses and selection response characterization.

Selectively bred FAST mice are highly susceptible, while SLOW mice are less susceptible, to the locomotor stimulant effects of ethanol. Heritability estimates indicate that approximately 15% of the variance in the FAST lines is of additive genetic origin, while low susceptibility is ostensibly nonheritable. Inbreeding has increased at the rate of 2% per generation, but fertility has been unaffected. Measurement reliability for sensitivity to this ethanol effect was high when measured in both circular (r = 0.6) and square (r = 0.7) open-fields. In addition, our results indicate that we have selected for differences in sensitivity to ethanol rather than for differences in habituation to the test environment. The difference in response to ethanol between FAST and SLOW mice extended to tests varying in duration, and to a range of ethanol doses. We conclude that the divergence between FAST and SLOW mice generalizes to related test parameters, and speculate that the genetic architecture underlying the locomotor stimulant response may be simpler than previously proposed.

Animals↗
PubMed1986

Effects of beta non-selective and beta 1 selective adrenergic blocking agents on glucagon secretion from isolated perfused rat pancreas.

To characterize beta-receptors which affect pancreatic A-cell activity, the effects of propranolol (beta non-selective blockade) and metoprolol (beta 1 selective blockade) were evaluated on epinephrine modulated insulin (IRI) and glucagon (IRG) release both in basal state and during metabolic stimulus (arginine 20 mM). The isolated perfused rat pancreas model with the exclusion of stomach and duodenum was used. Epinephrine infusion (at 10(-7) M) caused a prompt and sustained increase in basal IRG secretion and significantly potentiated glucagon release in response to metabolic stimulus. Insulin secretion was markedly suppressed by epinephrine both in basal conditions and during metabolic stimulus. Propranolol (at 10(-7) M) and metoprolol (at 10(-7) M) infusion clearly and similarly counteracted epinephrine stimulatory effects on IRG secretion but failed to elicit any significant effect on the epinephrine inhibited IRI release either in basal state or during the metabolic stimulus. These results suggest that, at least in the rat, the adrenergic stimulation of IRG release is mediated through a beta 1 receptor.

Animals↗