Search PubMed⌕ Search

Biomedical subjects

M D Taylor

Publications and source records attributed to M D Taylor.

At least 91 records · Page 5Linked to original sources
PubMed1991

Structure-activity studies of the C-terminal region of the endothelins and the sarafotoxins.

Peptides corresponding to the C-terminal 16-21 hexapeptide of the endothelins (-His-Leu-Asp-Ile-Ile-Trp) and sarafotoxins (a-c) (-His-Gln-Asp-Val-Ile-Trp) were prepared to study the role of the individual amino acids in receptor recognition and activation. Receptor binding in rabbit aorta, rabbit pulmonary artery, and rat heart ventricle is reported for all analogues. In addition, selected C-terminal hexapeptides have been evaluated functionally in two tissues (rabbit pulmonary artery and rat left atria). The C-terminal carboxylate, indole nitrogen, and nature of the aromatic residue are all important for receptor binding, but N-terminal acetylation has no effect. L-Amino acids are required in positions 19 and 21, whereas D-amino acids are tolerated in 17 and 18. D-Amino acids in positions 16 and 20 enhance the binding affinity of the hexapeptide in all three tissues. The nature of the basic residue at position 16 is important. Glu and Asn are acceptable substitutions for Asp18, although Ala leads to a substantial loss in binding. The binding of the C-terminal hexapeptide of SRTX-a, -b, and -c is less than ET[16-21] and this appears to be primarily due to the substitution of Gln for Leu17. None of the 16-21 hexapeptides showed any functional activity in the tissues studied.

Amino Acid Sequence↗
PubMed1991

Lifestyle changes in mild asthma during intermittent symptom-related use of terbutaline inhaled via 'Turbohaler'.

Beta 2-agonist therapy effectively relieves asthmatic symptoms, but an improvement in patient lifestyle has not been demonstrated. This open study in which patients acted as their own controls, assessed the efficacy and acceptability of intermittent symptom-related use of terbutaline inhaled via 'Turbohaler', and its influence on the lifestyle of 1133 inhaler-naive, mild asthmatics treated in general practice. A 1-week run-in period was followed by 4-weeks' treatment with inhaled terbutaline (500 micrograms as required). Peak expiratory flow rate (PEFR) and 'Turbohaler' technique were assessed at clinic visits. Diary cards, completed daily, assessed: the number of terbutaline inhalations, the relief obtained after use, the severity of asthma symptoms (cough, morning wheeze, nocturnal wheeze and wheeze on activity), and lifestyle indices (sleep disturbance, work/school days lost, limitation of normal activity). After terbutaline treatment, PEFR increased by 54 +/- 2 l/min (p less than 0.001), the severity of asthma symptoms was almost halved (p less than 0.001), with over two-thirds (65% to 76%) of patients reporting improvements in each variable, and the adverse effect of asthma on lifestyle was at least halved (p less than 0.001). Improvements in lung function, asthma symptoms and lifestyle were comparable for all sub-groups: adults (greater than 16 years), school-age children (6 to 16 years) and preschool children (less than or equal to 5 years). This study not only confirmed the efficacy and acceptability of intermittent symptom-related use of terbutaline inhaled via 'Turbohaler', but also demonstrated that its use enhanced patients' lifestyles.

Activities of Daily Living↗
PubMed1991

Budesonide once-daily in seasonal allergic rhinitis.

A randomized, parallel group, double-blind multi-centre study was carried out in 342 patients with symptomatic seasonal allergic rhinitis to assess the efficacy and tolerability of intranasal budesonide administered either as a single morning dose of 400 micrograms or as a 200 micrograms twice-daily dose, morning and evening, for 4 weeks. Both treatments improved the symptoms of seasonal allergic rhinitis; specific nasal symptom scores recorded daily by the patient being reduced. The proportions of patients symptom free after 4-weeks' treatment were 46% in the 400 micrograms once-daily group and 54% in the 200 micrograms twice-daily group, with total daily symptom scores recorded by diary cards reduced by 79% and 80%, respectively. The differences between the groups were not statistically significant. Sub-group analysis of patients allergic to grass pollen (n = 166) showed similar total symptom scores at each level of grass pollen exposure (no significant difference between treatment groups). Patients assessed both treatments to be effective (no significant difference between groups), with 65% of patients questioned stating a preference for a once-daily treatment given equal symptom control. Both treatments were equally well tolerated and few side-effects were reported.

Administration, Intranasal↗
PubMed1991

Intranasal budesonide once daily in seasonal allergic rhinitis.

A double-blind, parallel-group, multi-centre study was carried out in 248 patients with symptomatic seasonal allergic rhinitis to assess the effectiveness and tolerability of intranasal aqueous budesonide given as a single daily dose each morning of 400 micrograms compared with the conventional dosage regimen of 200 micrograms twice daily. After a 1-week run-in period during which only oral terfenadine was allowed for intolerable symptom relief, symptomatic patients were allocated at random to receive budesonide in one or other dosage regimen for 3 weeks. The results of assessments made by the physician at clinic visits and by patients recording daily data on diary record cards showed that specific nasal symptom incidence and severity were significantly (p less than 0.001) reduced in both treatment groups. The proportions of patients symptom-free at 3 weeks were 40% in the 400 micrograms once daily and 45% in the 200 micrograms twice daily group; in addition, mean nasal symptom scores from the daily diary cards were significantly (p less than 0.001) reduced in both groups, with a reduction in total symptom scores of 53% and 60%, respectively. The differences between the groups were not statistically significant. Total symptom scores were significantly (p less than 0.01) reduced in both dosage groups at all levels of pollen exposure. Patients rated treatment overall as being highly effective, mean scores being very similar in both groups, and tolerability was similar and good whether budesonide was given as a 400 micrograms once daily dose or as 200 micrograms twice daily. Assuming equal symptom control, 74% of patients stated they would prefer once daily to twice daily treatment.

Administration, Intranasal↗
PubMed1989

Pulmonary capillary pressures during hypoxia and hypoxemia: experimental and clinical studies.

Unlike the systemic circulation, the pulmonary vasculature constricts in response to hypoxia to divert blood flow to better-ventilated segments. The site of this response, the hypoxic pulmonary vasoconstriction, has been reported as precapillary in numerous experimental models of isolated animal lungs. In the present study, the response of intact chest dog and human lungs to hypoxia and hypoxemia, respectively, was also precapillary vasoconstriction. In dogs, hypoxia in the ipsilateral lung attenuated the normal vertical blood flow gradient. Contralateral hypoxia did not alter pulmonary regional blood flow, precapillary (Ra), postcapillary, or total pulmonary vascular resistance. In patients, an elevated alveolar-arterial oxygen pressure gradient of 50 to 150 torr resulted in significantly increased Ra. Further hypoxemia did not increase this response. In addition, the effective pulmonary capillary pressure did not bear a constant relationship to the pulmonary artery occlusion or wedge pressure (WP). Therefore, in patients in respiratory failure, WP does not reliably estimate hydrostatic pressure at the pulmonary capillaries.

Animals↗
PubMed1989

PD 122860: a novel dihydropyridine with sodium channel stimulating and calcium channel blocking properties.

The cardiac and vascular activities of ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4-pyridinyl-sulfonyl)methyl]-4-[2- (trifluoromethyl)phenyl]-3-pyridine carboxylase (PD 122860), a novel dihydropyridine, were investigated in vitro using rat heart and rabbit aorta, and compared with reference inotropic and vasodilator agents. In the rat heart, PD 122860 increased left ventricular contractility, decreased coronary resistance and altered the shape of the electrocardiogram T-wave. All three effects were observed at comparable concentrations of PD 122860. The inotropic response to PD 122860 was reversed by the Na+ channel blocker tetrodotoxin and blunted by the Na+-Ca++ exchange inhibitor dichlorobenzamil. The effects of tetrodotoxin and dichlorobenzamil on the inotropic response to the reference Na+ channel stimulant veratridine were comparable to PD 122860, whereas tetrodotoxin and dichlorobenzamil had no inhibitory effect on the inotropic responses to the adenylate cyclase stimulator forskolin or the Ca++ channel stimulant BAY K 8644. PD 122860 selectively relaxed potassium-contracted aortic rings and inhibited [3H]nitrendipine binding to rat brain membranes, suggesting that the vasodilator activity of PD 122860 is due to Ca++ channel blockade. In contrast to BAY K 8644, PD 122860 did not contract partially depolarized aortic rings, suggesting an absence of Ca++ channel stimulant activity. PD 122860 is a racemic mixture and both the vasorelaxant and [3H]nitrendipine binding inhibitory activities selectively reside in the (+)-enantiomer [(+)-PD 122860]. In contrast, the inotropic response resides with both enantiomers of PD 122860. It is therefore concluded that PD 122860 represents a unique dihydropyridine derivative which possesses both Na+ channel stimulating and Ca++ channel blocking activities.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers.

The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.

Animals↗
PubMed1987

Correlation of adenosine receptor affinities and cardiovascular activity.

Binding affinities of 28 adenosine analogs at A1 adenosine receptors (rat whole brain membranes, [3H]N6-cyclohexyladenosine, CHA), and at A2 adenosine receptors (rat striatal membranes, [3H]NECA) were compared to their EC25 values for decreasing heart rate and increasing coronary flow in the isolated rat heart. Heart rate (an A1 response) correlated with A1 binding affinity (r2 = 0.71, p less than 0.0001) but not with A2 binding affinity (r2 = 0.007, n.s.); conversely, coronary flow (an A2 response) correlated with A2 binding affinity (r2 = 0.83, p less than 0.0001) but not with A1 binding affinity (r2 = 0.05, n.s.). These results confirm that the brain A1 and A2 receptors, studied by binding methods, bear close similarities to their respective counterparts in the heart, studied by means of functional responses.

Adenosine↗
PubMed1986

Ribose-modified adenosine analogues as adenosine receptor agonists.

Analogues of the potent adenosine receptor agonist (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA), modified at N9, were prepared and evaluated for adenosine A1 and A2 receptor binding and in vivo central nervous system and cardiovascular effects. The modifications at N9 include deoxy sugars, 5'-substituted-5'-deoxyriboses, non-ribose sugars, sugar ring homologues, and acyclic sugar analogues. Most of the derivatives have poor affinity for adenosine receptors. Only minor modifications at C5' and C3' maintain potent binding. In general, those derivatives exhibiting in vivo behavioral or cardiovascular effects also have the highest affinity for adenosine receptors.

Adenosine↗
PubMed1985

Rapid analysis of bovine milk proteins by fast protein liquid chromatography.

The separation of bovine milk proteins by fast protein liquid chromatography has been investigated by ion-exchange chromatography on Mono Q and Mono S columns and by gel filtration on a column of Superose 12. The four major casein components (alpha s1, alpha s2, beta and kappa) as well as the minor gamma-caseins were generally well separated on the Mono S column with urea-containing buffers at pH 3.8 in as short a time as 7 min, although there was considerable overlap between alpha s1- and alpha s2-casein peaks. Peak area measurements indicated that the four caseins alpha s1, alpha s2, beta and kappa were present in total casein in the approximate proportions of 3.0:0.5:3.4:0.9, in good agreement with other literature values. Whey proteins were not separated on the Mono S column, but were all well resolved by rapid analysis on the Mono Q column at pH values between 6 and 8 in buffers free of urea or 2-mercaptoethanol. Both urea and 2-mercaptoethanol were required for casein analyses on the Mono Q column, but all the casein components were then separable over a broad pH range (5.0-11.0). While urea levels of 4.5-8.0 M and pH values of 7.0 to 8.0 were most generally useful, the resolution of some components was affected by urea concentration or pH, so conditions may have to be modified for specific analysis problems. The caseins were too similar in size to be separated on the Superose 12 column but high-speed gel filtration in as little as 15 min separated all the whey proteins well, molecular weight values obtained being in good agreement with literature values.

Animals↗
PubMed1985

Pharmacological protection of reoxygenation damage to in vitro brain slice tissue.

Pharmacological protection of central neural function against damage by hypoxia and reoxygenation was studied electrophysiologically and biochemically in hippocampal brain slices. Hypoxia causes a loss of both orthodromically and antidromically evoked potentials in CA1 pyramidal cell neurons. Damage due to hypoxia lasting more than 10 min cannot be restored by reoxygenation. Following pretreatment with methylprednisolone (10(-5) M), indomethacin (10(-5) M) or allopurinol (10(-5) M), reoxygenation after 10 min of hypoxia resulted in complete recovery of the evoked activity. Na+,K+-ATPase activity was not reduced by 10 min of hypoxia, but was reduced by 50% during the first 10 min of subsequent reoxygenation. Allopurinol (10(-5) M) protected against loss of this enzyme activity. The protective action by these drugs of both electrophysiological and biochemical aspects of neural function is consistent with the hypothesis that secondary ischemic damage is caused by the formation of oxygen-derived free radicals during reperfusion.

Allopurinol↗
PubMed1985

Classification of ischemic-induced damage to Na+, K+-ATPase in gerbil forebrain. Modification by therapeutic agents.

The activity of three forms of ATPase were examined in fractions of the brain of the gerbil treated with ethylene glycol-N-N-tetra-acetic acid (EGTA) under a variety of conditions of primary and secondary (reflow) ischemia. In animals which were unilateral ischemic (ligation of the right common carotid), damage to Na+, K+-ATPase alone was observed only after at least 6 hr of ischemia had elapsed. The phenomenon occurred in only symptomatic gerbils and was absent in animals which were either asymptomatic or only displayed partial neurological symptoms. Under conditions of bilateral cerebral ischemia, in which both carotid arteries were clamped, only irreversible ischemia (60 min) followed by reflow, was associated with highly significant damage to cerebral Na+, K+-ATPase. In regional studies of the forebrain involving ischemia for 60 min plus 30 min reflow, damage to Na+, K+-ATPase was evident in the cerebrum, hippocampus, striatum and thalamus, while the hypothalamus and olfactory bulb were spared. Pretreatment of gerbils with allopurinol, clonazepam or combinations of thiopental plus either indomethacin or methylprednisolone offered protection to cerebral Na+, K+-ATPase subsequent to secondary ischemia. With only minor exceptions (striatum) neither Ca2+, Mg2+- nor Mn2+-ATPase were altered by stroke or treatment with drugs.

Adenosine Triphosphatases↗
PubMed1984

Kinetics of GTP-modulation of adenylate cyclase in gerbil cerebral cortex after bilateral ischemia.

Changes in the sensitivity of adenylate cyclase and steady-state levels of cyclic AMP (adenosine 3',5'-monophosphate) occur in mammalian brain during ischemic episodes. In our previous investigation with the gerbil model of bilateral ischemia there was an indication that ischemic conditions produced an enhancement of GTP sensitivity of adenylate cyclase within the cerebral cortex. The present study employed a kinetic analysis to evaluate further the role of this GTP modulation of adenylate cyclase in the gerbil frontal cortex during periods of bilateral ischemia and recirculation. In general, after either 15-min (with or without 15-min reflow) or 60-min ischemia the Vmax to GTP (alone or with dopamine and norepinephrine) was increased. Under these conditions the ED50 for half-maximal enzyme activation was decreased, indicating a greater affinity of the transducer site for GTP during ischemia. However, if irreversible 60-min ischemia was followed by 15-min reflow the enzyme responses to GTP were now absent. An unexpected observation showed that the ED50 for GTP activation of cortical adenylate cyclase was likewise attenuated when sham-operated animals were compared to normal gerbils.

Adenylyl Cyclases↗
PubMed1984

Self-medication on a rehabilitation unit.

A self-medication program (SMP) has been designed and implemented as part of a multidisciplinary approach to rehabilitation. The four stages of the program, coordinated by a pharmacist, are: (1) patient assessment and introduction, (2) self-medication (SM) at the bedside, (3) SM at the nursing station, and (4) discharge assessment. Twenty-four patients, representing 52% of the patients introduced into the program, have successfully completed all stages. Severe physical impairment was not usually a deterrent to the completion of the program. All patients benefitted from the program by acquiring some skills in SM and by receiving additional motivation for improvement. The rehabilitation team received assurance that some patients could comply with their medication regimen after discharge.

Activities of Daily Living↗
PubMed1981

Preliminary evaluation of mesoionic 6-substituted 1-methylimidazo[2,1-b][1,3]thiazine-5,7-diones as potential novel prodrugs of methimazole.

A series of five 6-alkyl- and 6-aryl-mesoionic 1-methylimidazo[2,1-b][1,3]thiazine-5,7-diones was synthesized and found to produce 1-methyl-3H-imidazole-2-thione (methimazole) upon alkaline hydrolysis or treatment with amine or thiol reagents. The alkaline hydrolysis followed a second-order rate expression, being dependent on both substrate and hydroxide-ion concentrations. The rate constants for the five derivatives fell within 6-15 x 10(-2) liter/mole min at 40 degrees. These compounds were stable in aqueous acidic solutions and in human serum or rat liver homogenate under conditions producing rapid hydrolysis of the methimazole prodrug 1-carbethoxy-2-methylimidazole-2-thione (carbimazole).

Animals↗