Search PubMed⌕ Search

Biomedical subjects

A Neil

Publications and source records attributed to A Neil.

54 records · Page 3Linked to original sources
PubMed1985

Enzyme-linked immunosorbent assay of substance P and its metabolite SP 1-7. A comparison with RIA.

We have investigated enzyme-linked immunosorbent assay (ELISA) as a possible alternative to radioimmunoassay (RIA) for the detection and measurement of the neuropeptide substance P (SP) and its metabolite substance P1-7. The sensitivities were higher with ELISA than with RIA utilizing the same antisera. The intra-assay and inter-assay variation in ELISA was 1% and 13% respectively. The higher sensitivities are in part due to the standard curves having less steep slopes, and in part to lower IC50s in the ELISA. Since there was a good correlation between peptide levels in biological samples as determined by ELISA and RIA respectively, ELISA might be considered an attractive alternative to RIA.

Animals↗
PubMed1985

Detection and characterization of four binding sites for opioids in the mouse brain.

The binding sites labelled by 3H-dihydromorphine, 3H-ethylketocyclazocine and 3H-D-Ala2-L-Leu5-enkephalin in mouse brain membranes were characterized in cross-competition studies. The data was evaluated by simultaneous non-linear least-squares regression analysis with the "Ligand" program (Munson & Rodbard 1980), that had to be upgraded to handle more than three binding sites. By statistical analysis four different binding sites were identified. Three of the sites probably correspond to the pharmacologically well characterized mu, kappa and delta-opioid receptors, respectively, and their binding capacities relate as 1:1.5:2.5. Classification of the fourth site is more problematic. Using 3H-ethylketocyclazocine it had higher capacity than the others and bound ethylketocyclazocine with a relatively high affinity (Kd = 10 nM), dihydromorphine with a very low affinity (Kd greater than 10(-5)M) and showed no binding of D-Ala2-L-Leu5-enkephalin. In displacement studies, N-allylnorcyclazocine (SKF 10,047), though unselective, bound with highest affinity to the mu and the fourth site. Since naloxone did not bind to this fourth site, it can not be termed an opioid site in a strict sense, but it might have some relevance in view of non-naloxone-reversible effects reported for some opioids.

Animals↗
PubMed1984

Affinities of some common opioid analgesics towards four binding sites in mouse brain.

The selectivities of morphine, codeine, l-methadone and d-propoxyphene, towards the binding sites in mouse brain membranes labelled by 3H-dihydromorphine (DHM), 3H-ethylketocyclazocine (EKC) and 3H-D-Ala2-Leu5-enkephalin (DALE), were investigated. Of the four binding sites identified, three correspond to mu-, kappa- and delta-opioid binding sites or receptors, respectively. The fourth site has a high capacity and binds EKC with a high affinity, DHM with a very low affinity and does not bind DALE. In displacement studies, the relative affinities of morphine and methadone were quite similar towards the tree sites with highest affinity (mu much greater than kappa much greater than delta). Codeine and d-propoxyphene were mu-selective but did not differentiate between kappa- and delta-sites. At high concentrations I-methadone (Kd=6.7 microM), and d-propoxyphene (Kd=40 microM) bound to the fourth site, while morphine, codeine and naloxone were practically inactive. The binding selectivities of these drugs were quite different from those of metkephamid and U-50, 488 H, substances that are thought to exert their antinociceptive effects through delta- and kappa-receptors, respectively. It was concluded that while d-propoxyphene and codeine may partly act through other receptors than morphine, this is probably not the case for l-methadone.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1984

Studies on action mechanisms of morphine and 1-methadone in mice.

Chronically administered morphine and 1-methadone has previously been shown to yield different cross-tolerance patterns in mice. It was therefore tested if the two drugs differ in selectivities towards opioid binding sites in mouse brain membranes. Morphine and 1-methadone were found to show almost identical binding selectivities in vitro. It is suggested that the two drugs act by the same receptor(s), and that the observed asymmetry in cross-tolerance patterns could be due to differences in the receptor reserve for morphine- and 1-methadone-induced antinociception in mice.

Animals↗
PubMed1982

Morphine- and methadone-tolerant mice differ in cross-tolerance to other opiates. Heterogeneity in opioid mechanisms indicated.

Mice were rendered tolerant to morphine or 1-methadone by subcutaneous injections for 4 days. The antinociceptive activities of morphine, codeine, l-methadone and d-propoxyphene were determined in tolerant and control mice using the hot-plate test, and the respective ED50's were calculated by the up-and-down procedure of Dixon. An asymmetry in cross-tolerance patterns was found: While morphine-pretreated mice were tolerant to morphine only (with a dose-ratio tolerant: control of 5.2), methadone-pretreated mice were tolerant to all analgesics tested, and more so to morphine 5.2; l-methadone 3.0; codeine 2.7 and d-propoxyphene 1.9). The results are discussed in terms of heterogeneity in opioid receptor mechanisms.

Analgesia↗
PubMed1982

An improved foot-shock titration procedure in rats for centrally acting analgesics.

A foot-shock titration method for the measurement of antinociceptive activity in the rat has been developed. A new grid design is described which makes the use of scrambled shocks unnecessary. Thresholds for responses elicited at different levels of integration within the central nervous system are measured: Detection threshold, flexor reflex, coordinated jumping and vocalization. These thresholds were found to be stable over time in saline-treated rats. The two opioid analgesics morphine and d-propoxyphene increased these thresholds, each in a characteristic way. Morphine was more selective in its action and significantly more effective in increasing the vocalization threshold than the threshold for jumping, whereas d-propoxyphene increased both these thresholds to the same extent. Neither drug affected the detection threshold in low to moderate doses. The difference in pharmacodynamic profile is discussed in terms of heterogeneity of opioid receptor-effector mechanisms at different levels of the neuroaxis.

Analgesics↗
PubMed1981

Des-tyrosine1-gamma-endorphin increases the antinociceptive efficacy of morphine in the rat.

Repeated injections of des-tyrosine1-gamma-endorphin (DT gamma E) to rats subjectively increased sensitivity to handling. After 8 days of treatment, the animals were supersensitive to a low dose of morphine in the foot-shock test. Acute treatment with DT gamma E gave no significant increase in morphine sensitivity. The results indicate that DTgammaE given chronically interacts with opioid receptor-effector mechanisms.

Analgesia↗
PubMed1981

d-Propoxyphene acts differently from morphine on opioid receptor-effector mechanisms.

The actions of d-propoxyphene and morphine on opioid receptor mechanisms were compared. In assay measuring receptor binding selectivity in vitro, with dihydromorphine, naloxone and an enkephalin analogue as radioactive ligands, d-propoxyphene differed from morphine in having a higher relative affinity for sites occupied by the peptide. Naloxone was more potent in antagonizing morphine- than d-propoxyphene-induced antinociception in the mouse hot-plate test. In morphine-tolerant mice showing three-fold lower morphine sensitivity the antinociceptive efficacy of d-propoxyphene was unchanged. The results indicate differences in receptor-effector mechanisms between d-propoxyphene and morphine.

Animals↗
PubMedDate not supplied

Depression and anxiety as predictors of outcome after myocardial infarction.

OBJECTIVE: The objective of this study was to investigate the significance of emotional distress immediately after a myocardial infarction as a predictor of physical, psychological, and social outcomes and resource use. METHODS: In an epidemiological survey, demographic and cardiological data were obtained for all patients from a defined geographical area who had had a myocardial infarction (according to diagnostic criteria of the Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] trial). Hospital survivors were interviewed and were asked to complete self-report assessments on mental state and quality of life. Full replies were available at baseline for 347 subjects. Self-report follow-up questionnaire information was collected 3 months and 1 year later. RESULTS: Fifteen percent of patients scored as probable cases of anxiety or depression. They were more likely than noncases to report preinfarct distress and poor adjustment (as indicated on the 36-item Medical Outcome Study short form). There was an improvement at 3 months, but there was little overall or individual change after that time. Anxiety and depression did not predict subsequent mortality but did significantly predict poor outcome at 1 year on all dimensions of the 36-item short form quality-of-life measure and on specific measures of everyday activity and reports of chest pain, use of primary care resources, and secondary prevention lifestyle changes. CONCLUSIONS: Subjects who are distressed in the hospital are at high risk of adverse psychological and quality-of-life outcomes during the ensuing year. Our findings strengthen the argument for in-hospital identification and treatment of patients with depression and anxiety after myocardial infarction.

Adult↗
PubMedDate not supplied

The views of elderly patients and their relatives on cardiopulmonary resuscitation.

Little was previously known of the factors that may influence patients and relatives when asked to make decisions on cardiopulmonary resuscitation. Attitudes towards resuscitation in general appear to influence the wishes of elderly patients and their relatives for cardiopulmonary resuscitation. Knowledge of the procedure involved in cardiopulmonary resuscitation and its success rate and the patients' sex and health status do not influence their wishes.

Aged↗
PubMedDate not supplied

Garlic as a lipid lowering agent--a meta-analysis.

Garlic supplements may have an important role to play in the treatment of hypercholesterolaemia. To determine the effect of garlic on serum lipids and lipoproteins relative to placebo and other lipid lowering agents, a systematic review, including meta-analysis, was undertaken of published and unpublished randomised controlled trials of garlic preparations of at least four weeks' duration. Studies were identified by a search of MEDLINE and the ALTERNATIVE MEDICINE electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. Sixteen trials, with data from 952 subjects, were included in the analyses. Many of the trials had methodological shortcomings. The pooled mean difference in the absolute change (from baseline to final measurement in mmol/l) of total serum cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol was compared between subjects treated with garlic therapy against those treated with placebo or other agents. The mean difference in reduction of total cholesterol between garlic-treated subjects and those receiving placebo (or avoiding garlic in their diet) was -0.77 mmol/l (95% CI: -0.65, -0.89 mmol/l). These changes represent a 12% reduction with garlic therapy beyond the final levels achieved with placebo alone. The reduction was evident after one month of therapy and persisted for at least six months. In the dried garlic powders, in which the allicin content is standardised, there was no significant difference in the size of the reduction across the dose range of 600-900 mg daily. Dried garlic powder preparations also significantly lowered serum triglyceride by 0.31 mmol/l compared to placebo (95% CI: -0.14, -0.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗