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Biomedical subjects

D A Cook

Publications and source records attributed to D A Cook.

At least 91 records · Page 5Linked to original sources
PubMed1987

Mechanisms of arachidonic acid-induced contractions of canine cerebral arteries.

The effects of arachidonic acid in cerebral blood vessels has been examined using rings of canine cerebral arteries. Arachidonic acid produced dose-dependent contractions of this preparation even after mechanical removal of the endothelium. The contractions were not blocked by indomethacin or acetylsalicylic acid, both of which inhibit cyclooxygenase, but were inhibited by nordihydroguaiaretic acid which is a lipoxygenase inhibitor, BW 755c which blocks both pathways, and FPL 55712 which is an antagonist at leukotriene receptors. These data imply that arachidonic acid-induced contractions are mediated by products of the lipoxygenase pathway. Leukotrienes and cyclooxygenase products are generated by this preparation as shown by HPLC and radioimmunoassay and both LTC4 and LTD4 produce contractions in cerebral arteries lending further evidence in support of this suggestion.

Animals↗
PubMed1987

A controlled trial of nebulized aminoglycoside and oral flucloxacillin versus placebo in the outpatient management of children with cystic fibrosis.

Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract, completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo. The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo.

Administration, Inhalation↗
PubMed1987

Early production of 1,4,5-inositol trisphosphate and 1,3,4,5-inositol tetrakisphosphate by histamine and carbachol in ileal smooth muscle.

We have examined the time course of the formation of inositol mono-, bis-, tris, and tetrakisphosphates (InsP1, InsP2, InsP3, and InsP4, respectively) in slices of the longitudinal muscle of guinea pig small intestine that had been prelabeled with myo-3H-inositol. The agonists employed were histamine and carbachol. InsP3 increases immediately with a time course which is similar to that of the increase in contractile force and remains elevated for the rest of the incubation period. High performance liquid chromatography analysis revealed that InsP3 is composed of two isomers, the 1,4,5- and 1,3,4-isomers. The release of 1,4,5-inositol trisphosphate [Ins(1,4,5)P3] was followed by the rapid accumulation of InsP4 and later on by the formation of 1,3,4-inositol trisphosphate [Ins(1,3,4)P3]. Ins(1,3,4)P3 and InsP4 were identified by co-chromatography with the Ins(1,3,4)P3 and 1,3,4,5-inositol tetrakisphosphate prepared from 3H-Ins(1,4,5)P3 using a kinase from rat brain. The time course of accumulation of these compounds is consistent with a second messenger role of Ins(1,4,5)P3 in initiation of smooth muscle contraction.

Animals↗
PubMed1986

Effects of nimodipine on in vitro contractility of cerebral arteries of dog, monkey, and man.

Cerebrovascular spasm in the cynomolgus monkey does not appear to be modified by nimodipine. It is possible that cerebral arteries from this species are unusually resistant to the action of calcium antagonists. To test this hypothesis, parallel studies on the in vitro response of cerebral arteries from monkey, dog, and man have been carried out. Rings of basilar or middle cerebral artery were tested with potassium chloride, noradrenaline, 5-hydroxytryptamine, prostaglandin F2 alpha, and hemoglobin. The responses were then reexamined in the presence of various concentrations of nimodipine. There is a significant variation among species in sensitivity to nimodipine, the vessels from the monkey being more resistant to nimodipine than those from other species. There is, as expected, a considerable difference in the ability of nimodipine to block the different agonists. Responses to potassium chloride are blocked by low concentrations of nimodipine in all species, whereas noradrenaline and 5-hydroxytryptamine are more resistant. It is noteworthy that, in all species tested, hemoglobin and prostaglandin F2 alpha were antagonized poorly even by higher concentrations of nimodipine. If these agonists play a major role in the development of vasospasm and subsequent delayed ischemia, it may be that the calcium antagonists exert a beneficial effect by some mechanism other than dilation of spastic arteries.

Animals↗
PubMed1985

Effects of ethanol on the lipid composition of bovine vascular smooth muscle cells in culture.

Ethanol (50 mM) had no effect on the growth rate or viability of arterial smooth muscle cells over 3.5 days. The cholesterol:phospholipid ratio of the cells was unchanged after 7 days exposure. The major phospholipid components phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were unchanged by ethanol exposure. Sphingomyelin content fell significantly within 12 hr. There were major changes in the fatty acid composition of the phospholipids with a reduction in saturated fatty acids and an increase in unsaturated fatty acids.

Animals↗
PubMed1985

Temperature and histamine receptor function--what is really happening?

Early studies suggested that a low temperatures there was a transition of receptor type from an H1 to an H2 receptor when the temperature was reduced from 37 degrees C to temperatures below 20 degrees C. These original observations were based on the development of sensitivity of guinea-pig ileum to the H2 antagonist metiamide as the temperature was reduced. More recently, evidence from a number of laboratories has cast doubt on the existence of a simple H1-H2 receptor transition, but there is abundant evidence that there are major changes in the response of a variety of smooth muscle preparations to histamine at reduced temperatures. The evidence in regard to alterations in histamine response at low temperatures is reviewed, some new evidence presented, and a model which is consistent with most of the observations is suggested.

Animals↗
PubMed1985

The binding of [3H]mepyramine to histamine H1 receptors in monkey brain.

Several laboratories have reported ligand binding studies using radioactive histamine H1 antagonists to label the H1 receptors in mammalian brain. We have extended these studies to a detailed examination of the binding of [3H]mepyramine to monkey brain and have shown that the distribution is similar to that in man, with specific binding sites being concentrated in the frontal cortex with relatively low binding to the pons and basal ganglia. The binding shows a single saturable component with a KD of about 1 nM and a Hill plot slope close to unity. These observations are the same for all structures tested. Comparison with data from other laboratories suggests that in this species, the histamine receptor is the same as that in peripheral tissues. From Ki values for various ligands and comparison of KD estimates in other species, the receptor seems to be essentially identical to the H1 receptor in central and peripheral tissues of the guinea pig and also to that in human brain. The rat and possibly the dog have minor differences from the monkey in terms of KD values for [3H]mepyramine binding.

Aminopyridines↗
PubMed1984

A computer-assisted technique for analysis and comparison of dose-response curves.

We report a computer-assisted technique for comparison of dose-response curves. Slopes and ED50 values are calculated on the percentage response and the probit transformation of that response, and these are then compared by using an analysis of variance. The technique is much more sensitive than the usual approach of point-by-point comparison and enables several curves to be compared simultaneously. The program, which is written in APL, is interactive and can be used from a terminal by those unfamiliar with computing.

Analysis of Variance↗
PubMed1984

Detection of endothelium in cerebral blood vessels.

An increasing body of evidence implies that the results of pharmacological studies of blood vessels may depend on the presence of an intact layer of endothelial cells inside the blood vessels. This is often inadvertently removed during the early part of the experiment and it is thus necessary to have some means of determining whether the endothelium is intact or has suffered extensive damage. Previous reports describe a stain that will enable the endothelial cells to be visualized, however we find that in the cerebral vasculature this approach is unsatisfactory in that it provides a gross underestimate of the amount of intact endothelium. A modification of the original procedure is described that provides results that correspond well with those of scanning or transmission electron microscopy.

Animals↗
PubMed1984

The mechanism of the histamine-induced desensitization of guinea-pig ileum.

Histamine and the selective H1 receptor agonist 2-pyridylethylamine show cross-desensitization when tested in guinea-pig ileum. The H1 receptor blocking agent produces a smaller parallel shift in desensitized tissues when compared with non-desensitized controls. We conclude that desensitization in this system occurs at the receptor level and is reflected by a decreased sensitivity to both agonists and antagonists.

Animals↗
PubMed1984

Recent advances in histamine research: closing remarks.

In an attempt to highlight some of the more interesting problems of current histamine research several issues have been considered, including the difficulty of finding selective drugs, particularly agonists, the problems of receptor and organ selectivity, and the mystery of the biological function of histamine receptors in smooth muscle. These problems were raised in one form or another by speakers at this symposium and it is clear that despite the many exciting advances reported in the earlier communication many mysteries remain.

Animals↗