Search PubMed⌕ Search

Biomedical subjects

D W Oliver

Publications and source records attributed to D W Oliver.

48 records · Page 3Linked to original sources
PubMed1994

Effect of sumatriptan on cerebral blood flow in the baboon model.

Changes in cerebral blood flow are implicated to be important in the pathophysiology of migraine. Furthermore, serotonin (5-HT) is known to be the most important substance in the etiology of migraine. Sumatriptan (CAS 103628-46-2), a 5-HTID receptor agonist was recently introduced in the treatment of migraine. In the present study a baboon model was used to investigate the changes in cerebral blood flow due to anaesthesia and pharmacological interventions using 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) and single photon emission computed tomography (SPECT). The effect of sumatriptan on cerebral blood flow was investigated after 10 min and again after 23 min, with the animal under anaesthesia, i.e. induction with ketamine and maintenance on thiopental. Sumatriptan did not alter the cerebral blood flow during the 10 min procedure. However, sumatriptan reversed the increased cerebral blood flow due to the prolonged anaesthesia (23 min), lowering the cerebral blood flow by more than 20%. No significant changes in the biochemical parameters (blood pressure, heart rate, pO2 and pCO2) were observed. These results also suggest that sumatriptan reverses the increased cerebral blood flow most likely via 5-HTID receptor stimulation.

Anesthesia↗
PubMed1993

Dose response from pharmacological interventions for CBF changes in a baboon model using 99Tcm-HMPAO and SPECT.

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and 99Tcm-hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted (P > 0.05). The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then followed a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO2 showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide.

Acetazolamide↗
PubMed1993

Drug effects on cerebral blood flow in the baboon model--acetazolamide and nimodipine.

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.

Acetazolamide↗
PubMed1992

South African traditional herbal medicines used during pregnancy and childbirth.

Many black South African women use traditional herbal remedies as antenatal medications or to induce or augment labour. Very little is known about the pharmacology and potential toxicity of the plants used in these herbal remedies. The ethnic background and traditional usage of these remedies was researched and a literature survey revealed that 57 different plants were used in herbal remedies during pregnancy and childbirth. Several of these plants are poisonous and details of their toxicity are given.

Black or African American↗
PubMed1992

Synthesis and anti-HIV-1 activity of N-hydroxy-N1-aminoguanidines.

The synthesis of 13 new Schiff bases of N-hydroxy-N1-aminoguanidines starting from thiosemicarbazide are reported. These new derivatives were for the first time tested against infection by the Human Immunodeficiency Virus Type 1 (HIV-1) using the human T-lymphocyte cell line. Four N-hydroxy-N1-aminoguanidines exhibited HIV-1 inhibition in the micromolar range. The most active compound, [1-(1'-chloro-2'-hydroxy-3'-methoxybenzylidene)amino]-3-hydroxy guanidine inhibited HIV-1 by 96% at 10 micrograms/ml concentration. All the derivatives exhibited substantial cytotoxicity at 320 micrograms/ml concentration. The results indicate that the activity against HIV-1 increases with increasing hydrophobicity and substituents with electron-donating properties.

Antiviral Agents↗
PubMed1991

High-resolution solid-state carbon-13 nuclear magnetic resonance spectra of mofebutazone, phenylbutazone, and oxyphenbutazone in relation to X-ray crystallographic data.

The solid-state 13C NMR spectra of mofebutazone, phenylbutazone, and oxyphenbutazone monohydrate and anhydrate are presented. The crystal structures of these pyrazolidinedione derivatives, obtained by single-crystal X-ray analysis, were previously reported, revealing distinct differences in crystal structure. In this report, the chemical shift values observed for the solid-state 13C spectra are related to the chemical environment of the various carbon atoms and compared with the crystallographic data. Results indicate that solid-state NMR spectroscopy is potentially useful in the study of drugs in the solid state.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Synthesis and biological activity of D3-trishomocubyl-4-amines.

The D3-trishomocubyl system was prepared from tertiary pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ols 5 in one step by using a modified Ritter reaction yielding only one of the possible two geometrical isomers of 4-amino-3-alkyl (or aryl)-D3-trishomocubane (8). Promising antagonism of reserpine-induced catalepsy was exhibited by these compounds which compared favorable with that of amantadine. Weak to mild anticholinergic properties were observed during the reduction of oxotremorine induced tremor and salivation procedure. Acute toxicities similar to that of amantadine were observed for some of these compounds. D3-Trishomocubyl-4-amines appeared as a promising new class of anti-Parkinson agents.

Animals↗
PubMed1991

Antiviral properties of 4-amino-(D3)-trishomocubanes.

Two amino derivatives of (D3)-Trishomocubanes recently synthesized were evaluated for their in vivo and in vitro activities against selected viruses. Both these derivatives exhibited promising in vivo activity against Herpes simplex Type II and Influenza A2/Taiwan, comparable with aciclovir and amantadine, respectively. No in vitro activity was observed for both compounds against Herpes simplex Types I and II and Rhinovirus 1A.

Acyclovir↗
PubMed1989

Preliminary isolated organ studies using an aqueous extract of Clivia miniata leaves.

An infusion of Clivia miniata leaves is a traditional medicine taken by Black South African women to induce or augment labour. A boiling water extract of C. miniata leaves was studied for its pharmacological effects on rat uterus and ileum. The extract caused concentration-dependent contractions in both the uterus and ileum, but at a fraction of the intrinsic activity of acetylcholine. When the organs were pretreated with the extract before the cumulative addition of either oxytocin or acetylcholine, the extract augmented the initial response of the organs to the reference drugs. The frequency of contractions in the spontaneously contracting uterus was increased by the presence of the extract. C. miniata extract, however, inhibited the maximal response of the ileum to acetylcholine in a non-competitive way. It did not affect the maximal response of the uterus to either oxytocin or acetylcholine.

Acetylcholine↗
PubMed1987

A model for agonists acting directly as well as indirectly.

A theoretical model is presented to describe the receptor interaction of a drug which possesses indirect as well as direct pharmacological action. Sets of theoretical log concentration-effect curves predicted by this model are presented. The model predicts that the shape of the log concentration-effect curves may be sigmoid (S-shaped), biphasic (bell-shaped) or composed of a combination of two sigmoid curves, joined together by a plateau. The theoretical predictions are comparable with the results obtained from an experimental study.

Animals↗
PubMedDate not supplied

The medical effects of postulated accidental release of radioactive material from Heysham Nuclear Power Station.

The effects of a postulated reactor accident at one of the four AGRs at Heysham, NW England, have been studied, assuming a 10% release of the radioactive core. Methods used are a computer program TIRION, analysis of the radiation doses from the Chernobyl release of 1986 and the Windscale fire of 1957. Fatal cases predicted are 200 on-site, 3000 within 30 km and 250,000 in the cloud paths over Northern England. The results would suggest the incidence of fatal cancer would increase from roughly 20% to 27% in the postulated exposed population of 3.6 million.

Accidents, Occupational↗