Search PubMed⌕ Search

Biomedical subjects

N Moore

Publications and source records attributed to N Moore.

At least 55 records · Page 3Linked to original sources
PubMed1994

Estrogen-progesterone and 8-OH-DPAT attenuate the lordosis-inhibiting effects of the 5-HT1A agonist in the VMN.

Ovariectomized rats were treated for 2 consecutive weeks with 25 micrograms estradiol benzoate followed 48 h later with 500 micrograms progesterone. Bilateral infusions of 200 ng 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the ventromedial nucleus of the hypothalamus (VMN) inhibited female sexual behavior on the first but not the second week of hormone priming. Such attenuation on the second week of priming did not appear to result from an enhanced receptivity of the female rats since there were no differences in the L/M ratios prior to drug infusion; nor was the attenuation a consequence of infusion-induced VMN damage since neither saline nor 8-OH-DPAT preinfusions prevented the later inhibitory effects of 8-OH-DPAT on lordosis behavior. However, preinfusion with 8-OH-DPAT may have reduced the duration of the inhibition. Hormone priming (without any VMN infusion) also partially attenuated the effect of 8-OH-DPAT. Both hormone priming and treatment with 8-OH-DPAT were required to eliminate the effects of the second 8-OH-DPAT treatment. Thus, the present results suggest that gonadal hormones, alone, slightly attenuate the effects of agonist activation of 5-HT1A receptors involved in the inhibition of lordosis behavior; that agonist activation of 5-HT1A receptors also produces a slight attenuation; but that both treatments together have a robust protective action against the inhibitory effect of a 5-HT1A agonist on female lordosis behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Plasma 5-fluorouracil and alpha-fluoro-beta-alanin accumulation in lung cancer patients treated with continuous infusion of cisplatin and 5-fluorouracil.

This study was undertaken to investigate the day-to-day pharmacokinetic variability of 5-fluorouracil (5FU) given as a continuous i.v. infusion concomitantly with cisplatin. Ten lung cancer patients were investigated during the first course of chemotherapy. All patients had advanced, previously untreated, inoperable non-small-cell lung cancer. They received continuous infusions of cisplatin given at 100 mg/m2 over 5 days and of 5FU given at 1 g/m2 daily from day 2 to day 5. Both drugs were infused i.v. for 24 h/day at a constant rate with a volumetric pump. Blood samples were drawn from day 2 to day 5, every 4 h from 8 a.m. to 8 p.m. and every 2 h during the night (8 p.m. to 8 a.m.). Plasma 5FU and FBAL concentrations were determined simultaneously by gas chromatography-mass spectrometry. Plasma 5FU concentrations varied widely over the 4-day treatment course for each patient. Despite continuous constant-rate 5FU administration, plasma 5FU concentrations were significantly lower between 8 a.m. and 8 p.m. than during the night. Mean plasma concentrations of 5FU and FBAL increased significantly from the 1st day (0.42 and 1.19 micrograms/ml for 5FU and FBAL, respectively) to the 4th day of 5FU infusion (0.67 and 1.78 micrograms/ml for 5FU and FBAL, respectively). Further study is warranted to elucidate the mechanisms of the observed increase in plasma 5FU concentrations as well as its relationship with cisplatin coadministration and to assess the clinical relevance of this plasma 5FU accumulation.

Aged↗
PubMed1994

Endothelins. A potential target for pharmacological intervention in diseases of the elderly.

The existence of vasoconstrictive factors originating from the endothelium was confirmed by the description of endothelin, a 21-amino-acid peptide derived from a series of precursors, preproendothelin and a 38-amino-acid big endothelin. Three isoforms of endothelin, endothelin-1, -2 and -3, and 3 receptors (ETA, ETB and ETC) have been described and cloned. The cellular mode of action of endothelin seems to involve the modulation of intracellular calcium (through inositol trisphosphate, diacylglycerol and phospholipase C) and activation of calcium channels. The effects of endothelin are predominantly on the cardiovascular system. Its major effect is vasoconstriction, both systemic and pulmonary, with additional positive chronotropic and inotropic effects on the heart. It has also been implicated in homeostatic regulation of kidney microcirculation, and has powerful mitogenic effects on fibroblasts and smooth muscle cells. Many additional effects have been described on the endocrine system and on other systems. However, the clinical relevance of such effects is uncertain. Increased plasma endothelin levels have been reported in many diseases, but as yet it is not certain whether they are a cause or a consequence of the pathology. Pathologies most probably related to endothelin dysfunction are the vasospastic diseases, especially vasospasm after subarachnoid haemorrhage. Endothelin could be implicated to a lesser measure in diseases typical of the elderly population, such as hypertension or atherosclerosis. Drugs are being developed which act on endothelin metabolism, the most promising of which appear to be the inhibitors of endothelin converting enzyme and endothelin receptor antagonists. Some already existing drugs, such as calcium channel blockers or angiotensin converting enzyme inhibitors, probably act at least in part by interfering with endothelin metabolism or effects.

Aged↗
PubMed1994

A comparison of the hemodynamic effects of urapidil, prazosin, and clonidine in healthy volunteers.

Urapidil is an antihypertensive agent known to have central 5HT1A agonistic properties in addition to alpha-1 blocking effects. To assess the importance of these effects, we compared the hemodynamic effects of a single oral dose of urapidil (U, 60 mg) with those of prazosin (Pr, 2 mg), clonidine (Cl, 0.15 mg), and placebo (Pl), at rest, during orthostatic tilt, and during submaximal graded bicycle exercise tests, in a double-blind randomised crossover study in 24 healthy male volunteers. The variables studied were heart rate, mean blood pressure, cardiac index by bioimpedance, systemic vascular resistance index (SVRI), and plasma norepinephrine. Baseline values before drug administration were identical. At rest, during tilt, and during identical exercise, compared to placebo, urapidil and prazosin caused similar decreases in SVRI, with a smaller increase in HR after urapidil than after prazosin (p < 0.01), and without any difference in BP. Both drugs increased norepinephrine in a similar manner. In contrast, clonidine decreased blood pressure (p < 0.01) and norepinephrine (p < 0.01) with no difference in heart rate or SVRI. In conclusion, at rest, during tilt and during exercise, urapidil and prazosin have similar vasodilating effects, but the sympathetic stimulation is less and the parasympathetic stimulation greater after urapidil than after prazosin, probably indicating a centrally acting effect of urapidil. However, the sympathoinhibitory effect of urapidil is less marked than that of clonidine.

Adult↗
PubMed1993

Use of an enzyme-linked immunosorbent assay (ELISA) to measure the expression of the K88 fimbrial antigen by enterotoxigenic Escherichia coli (ETEC).

A solid-phase enzyme-linked immunosorbent assay (ELISA) has been developed to detect and quantify the K88 fimbrial adhesin antigen. The assay was used to detect cell-bound antigen present in bacterial suspensions and cell-free K88 antigen present in extracts. Comparable amounts of K88 antigen were detected with whole bacteria and in the equivalent extracts. The assay was used to compare the expression of the K88 antigen by one laboratory strain (K12:K88ab) and three wild-type strains (O8:K87:K88ab:H19, O8:K87:K88ac:H19 and K88ad) of enterotoxigenic Escherichia coli (ETEC) during cultivation with eight medium types and two medium forms. Determination of the expression of K88 during unshaken batch culture revealed a correlation between growth phase and expression, with maximal concentrations being detected during late log to early stationary phase. Colony blotting experiments demonstrated that expression of the K88 antigen was under quantitative and not qualitative control.

Antigens, Bacterial↗
PubMed1993

Cough and ACE inhibitors.

Explore the source record for details and available documents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Lack of effect of magnesium-aluminium hydroxide on the absorption of theophylline given as a pH-dependent sustained release preparation.

Antacids can modify the pharmacokinetic parameters of sustained-release preparations of theophylline by changing the gastric pH. Though this has been studied with various theophylline/antacid combinations, the specific preparations investigated here have not previously been tested. The objective of the study was to assess any change in the availability of theophylline from a sustained-release preparation (SR), induced by the coadministration with an antacid. The study was designed as a double-blind randomized crossover trial in the Pneumology Departments of three general hospitals. Fifteen patients were studied. They all had stable asthma treated with theophylline and no major organ failure or gastro-intestinal lesions requiring the use of antacids. The antacid (aluminium hydroxide 800 mg and magnesium hydroxide 800 mg), or placebo, tid, was added to a stable regimen of theophylline SR bid, for 4 days, in crossover fashion. Plasma theophylline concentrations were measured before and 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h after the morning dose of Armophylline on the fourth day of each treatment period; the maximum plasma concentration (Cmax), and time to Cmax (tmax) were noted, and the area under the 24-h time-concentration curve (AUC0-24) and mean plasma concentration (Cmean) were computed. Peak expiratory flows on the same day, before and 3, 6 and 12 h after the morning dose of Armophylline were also measured. There was no change in any of the parameters studied. The addition of the antacid to theophylline, each given according to standard clinical practice, did not modify the pharmacokinetics of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Protein binding of digitoxin, valproate and phenytoin in sera from diabetics.

Chronic hyperglycaemia results in glycation of serum albumin and might affect the binding of drugs. The aim of the present study was to compare, using an equilibrium dialysis method, the protein binding of therapeutic concentrations digitoxin, valproate and phenytoin in sera from 70 insulin-dependent diabetics and 25 controls. Drug concentrations were measured by fluorescence immunopolarisation. Glycated albumin was measured by laser nephelometry after affinity chromatography. In sera from diabetics, protein binding of digitoxin (88.8 versus 89.9%) was unchanged; the protein binding of valproate (75.2 versus 80.7%) and phenytoin (67.9 versus 75.3%) was significantly decreased, but with no correlation with the concentration of glycated albumin. We conclude that the difference in protein binding between diabetic and control sera is due to glucose-independent modification of albumin in diabetics.

Adult↗
PubMed1993

Inhibitory effects of the 5-HT1A agonists, 5-hydroxy- and 5-methoxy-(3-di-n-propylamino)chroman, on female lordosis behavior.

Sexually receptive, intact, proestrous rats were infused bilaterally into the ventromedial nucleus of the hypothalamus with one of several serotonin (5-HT) agonists and with the endogenous ligand, 5-HT. Serotonin (2000 ng) and the 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT (200 ng)], 5-methoxy-3-(di-n-propylamino)chroman [5-MEO-DPAC (200-2000 ng)] and 5-hydroxy-3-(N-di-n-propylamino)chroman [5-OH-DPAC (200-2000 ng)] inhibited female lordosis behavior within 10 min of the infusion. The rank order of the effectiveness of these compounds was 8-OH-DPAT > 5-OH-DPAC > or = 5-MEO-DPAC > 5-HT. The nonselective 5-HT agonist, 1-(m-trifluoromethyl) piperazine [TFMPP (2000 ng)], did not reduce lordosis behavior. In addition to their reduction of lordosis behavior, the 5-HT1A agonists elicited resistive behavior toward the male's attempts to mount. There were minimal effects of the 5-HT1A agonists on either quality of the lordosis reflex or on proceptivity. However, rats pretreated with TFMPP and infused with 8-OH-DPAT 1 hr later, did show a transient suppression of lordosis quality. These results provide further evidence that the ventromedial nucleus of the hypothalamus contains 5-HT1A sites, the activation of which reduces lordosis behavior in regularly cycling, proestrous rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Metabolic effects of propofol and flunitrazepam given for sedation after aortic surgery.

Sixteen patients who had undergone abdominal aortic surgery were allocated randomly to receive either propofol (total dose 3.2 (SEM 0.3) mg kg-1 h-1) or flunitrazepam (total dose 15 (2) micrograms kg-1 h-1) for 16 h after operation. Metabolic effects of sedation were assessed using a Deltatrac metabolic monitor. Initiation of sedation induced a 25% decrease in VO2 in both groups. The decrease was about 40% at 16 h. VO2 increased within 30 min after discontinuation of propofol and stabilized at values considerably less than the immediate postoperative value. A similar but slower increase was noted with flunitrazepam. While the propofol loading dose reduced the Buffington index and should therefore be avoided, no cardiovascular side effects were noted with the maintenance infusion. Weaning from ventilatory support was achieved within 15 (2) min and 264 (108) min after discontinuation of propofol and flunitrazepam, respectively.

Aortic Aneurysm, Abdominal↗