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Biomedical subjects

A Bennett

Publications and source records attributed to A Bennett.

At least 163 records · Page 9Linked to original sources
PubMed1985

Effects of isoxicam and other non-steroidal anti-inflammatory drugs on arachidonic acid metabolism by rat peritoneal leucocytes.

Inhibition of prostaglandin formation from [14C]arachidonic acid by rat peritoneal leucocytes occurred with nonsteroidal anti-inflammatory drugs, their order of potency being indomethacin greater than piroxicam greater than naproxen greater than ibuprofen greater than isoxicam. At the lowest concentration tested (1 microgram ml-1), indomethacin markedly increased the accumulation of lipoxygenase products in the cell incubates. Naproxen, ibuprofen or piroxicam 1 or 10 micrograms ml-1 resulted in smaller increases of lipoxygenase products, and there was only a small rise with these concentrations of isoxicam.

Animals↗
PubMed1985

A new method for studying cell growth in suspension, and its use to show that indomethacin enhances cell killing by methotrexate.

Microturbidimetry has been used to measure the growth of cells in suspension. Disaggregated mouse NC carcinoma cells in culture medium were added to the wells of a microtitre test plate and incubated. Absorbance of 600 nm light was measured daily for 4 days using a microplate reader. As the cells grew, light absorbance increased. Methotrexate 2-40 ng ml-1 reduced cell growth; this effect was increased by indomethacin 1 microgram ml-1, possibly by displacing methotrexate from its binding by serum protein or by enhancing cell uptake of methotrexate. Similar results were obtained by conventional clonogenic assays. The new technique offers simplicity, better reproducibility, and substantial savings in time and cost.

Animals↗
PubMed1985

Regulation of cell growth by vitreous humour.

Extracts of normal vitreous have been found to inhibit angiogenesis in two animal models: tumour-induced neovascularization in the rabbit corneal micropocket and retinal extract-induced angiogenesis in the chick chorioallantoic membrane assay. Using in vitro assays, we have found recently that an extract of bovine vitreous, free of hyaluronic acid, inhibits proliferation of cells in the aortic wall, i.e. endothelium and smooth muscle cells, as well as capillary and corneal endothelium. The inhibition is dose-dependent, as determined by either cell count or [3H]thymidine incorporation, and not due to cytotoxicity, as demonstrated with a double-label thymidine assay. The inhibitor is trypsin-sensitive and heat-stable (95 degrees C for 10 min). Conversely, proliferation of pericytes, lens epithelium and fibroblasts (dermal and corneal) was stimulated by the vitreous extract. This mitogenic activity was heat-labile. Growth of pigment epithelium and several tumour cell lines was unaffected. The data demonstrate that normal vitreous contains a heat-stable growth inhibitor specific for endothelium and smooth muscle cells, and a non-specific heat-labile mitogen. The paradoxical effect of this antiangiogenic factor on arterial and capillary contractile cells, smooth muscle and pericytes, suggests a basic difference in the regulation of the two vasculatures. The results suggest that a substance in normal vitreous may be important in controlling neovascularization that results from diabetic and other retinopathies, and could be useful for inhibiting tumour-induced angiogenesis.

Animals↗
PubMed1984

The production of arachidonate lipoxygenase products by rat intestine is increased by phenolphthalein.

Rat isolated intestine incubated in Krebs solution converted exogenous [14C]arachidonic acid into products that chromatographed with prostaglandins, leukotriene B4 and 5-hydroxy-eicosatetraenoic acid. The accumulation of these products was increased by phenolphthalein 3.14-1570 microM and reduced by indomethacin 2.8 microM. This raises the possibility that laxation by phenolphthalein involves the formation of arachidonate lipoxygenase and cyclo-oxygenase products.

Animals↗
PubMed1984

The biological activities of phthalate esters on rat gastric muscle.

Monoethylhexyl phthalate, at concentrations that can occur in blood stored in plastic bags (0.1-0.5 mg/ml), reduced contractions of rat isolated gastric fundus to PGE2 and acetylcholine; the diethyl compound was less effective. In contrast, dibutyl phthalate (1 and 10 micrograms/ml) and, to a lesser extent di-isobutyl phthalate, increased the muscle tone. These results are discussed in relation to blood transfusion, and to structural similarities between phthalates and prostaglandins.

Animals↗
PubMed1984

The effect of garlic extracts on contractions of rat gastric fundus and human platelet aggregation.

Garlic has been extracted and separated chromatographically into various fractions which show different degrees of activity as inhibitors of platelet aggregation and smooth muscle. The most potent smooth muscle inhibitor fraction had little activity on platelet aggregation, but microgram ml-1 concentrations greatly reduced the contractions of rat gastric fundus to prostaglandin E2 and acetylcholine. Material in this fraction may contribute to some of the claimed therapeutic effects of garlic involving smooth muscle. Its identity is not known, but is different from allyl sulphide, dimethyl sulphide and diallyl disulphide. These compounds eluted earlier on liquid chromatography than the most active fraction, and they showed only modest inhibitory activity against prostaglandin E2 and acetylcholine on rat fundus.

Acetylcholine↗
PubMed1984

Characterization of insulin-like growth factor I receptors on cultured rat bone cells: regulation of receptor concentration by glucocorticoids.

A specific receptor for insulin-like growth factor I (IGF-I) has been demonstrated in cultured fetal rat osteoblast-like bone cells. Specific binding of [125I]IGF-I to bone cells incubated at 15 C reached a steady state by 5 h. Half-maximal inhibition of [125I]IGF-I binding by unlabeled IGF-I was observed at 7 ng/ml. Multiplication-stimulating activity, insulin, and proinsulin were less effective than unlabeled IGF-I in competing for receptor occupancy. Scatchard analysis showed a curvilinear plot, with a Ka similar to that observed in human fibroblasts. Incubation of cell monolayers with glucocorticoids resulted in a concentration-dependent increase in [125I]IGF-I binding. This increase in [125I]IGF-I binding was dependent on cell density. After a 2-day exposure to dexamethasone, no increase in binding was observed in sparsely plated cells; however, an increase in binding was observed after 3 days in culture (log phase) and was maximal by 5 days (peak log phase). These data indicate that rat bone cells possess a specific receptor for IGF-I with binding characteristics similar to those reported in human fibroblasts, and that IGF-I receptor concentrations are increased by exposure to glucocorticoids. A role for glucocorticoids and IGF-I in rat bone proliferation is suggested by these findings.

Animals↗
PubMed1984

Human colonic pharmacology.

This paper briefly reviews human colonic innervation, and the effects of acetylcholine, noradrenaline, histamine, 5-hydroxytryptamine, polypeptides and prostaglandins. It discusses the actions of drugs used to treat disorders of colonic motility and fluid transport, and the possible ways they may exert their effects.

Adrenergic alpha-Antagonists↗
PubMed1984

Gastric mucosal formation of prostanoids and the effects of drugs.

Prostanoids can be formed throughout the gastrointestinal tract, and qualitative gas chromatography--mass spectrometry has shown that human gastric mucosa can produce PGD2, PGE2, PGF2 alpha 6 keto-PGF1 alpha, thromboxane A2 and lipoxygenase material. Quantitative gas chromatography--mass spectrometry has shown that human gastric mucosa homogenized in Krebs' solution yields mainly 6-keto-PGF1 alpha, with smaller amounts of PGD2 PGE2 and PGF2 alpha. However, the sources of these products and their roles in the gastric mucosa have not been fully elucidated. Recent research from other laboratories indicates that thromboxane formation may be important in gastric ulceration. Our studies with rats in vivo have detected no significant effect of carbenoxolone or deglycyrrhized liquorice on the content of radio-immunoassayable PGE, 6-keto-PGF1 alpha and TXB2 extracted from rat gastric corpus mucosa. The anti-ulcer effect of these drugs in rats therefore does not seem to involve prostanoids.

Animals↗
PubMed1983

Synthesis of thromboxane B2 in uraemia and the effects of dialysis.

The generation of thromboxane B2 (TxB2) from its natural precursor, arachidonic acid, was studied in vitro in order to assess further the prostaglandin pathway in the platelets of patients with chronic renal failure. Some, but not all patients with conservatively treated uraemia synthesised significantly less TxB2 then controls and the same patients were also hypo-aggregable to arachidonic acid. The synthesis of TxB2 appeared normal in a group of patients on chronic ambulatory peritoneal dialysis (CAPD). In contrast, a group of patients on long-term maintenance haemodialysis produced significantly greater amounts of TxB2 and were hyper-aggregable to arachidonic acid, a finding which may be relevant to the high incidence of atherosclerosis and vascular disease in these patients.

Adult↗
PubMed1983

Levels of insulin-like growth factors I and II in human cord blood.

Levels of insulin-like growth factors I and II (IGF-I and IGF-II) and somatomedin peptide content (SMPC) were measured in 32 normal term and 11 preterm infants. After acid chromatography to remove somatomedin-binding protein, SMPC was measured by placental membrane radioreceptor assay, while plasma IGF-I and II concentrations were measured by specific RIAs. SMPC levels in term infants were significantly below normal adult levels [0.49 +/- 0.13 (+/- SD) U/ml for infants compared to 1.30 +/- 0.25 U/ml for adult males]. IGF-I levels in term infants were also low, averaging 113 +/- 35 ng/ml for infants; the normal adult levels is 184 +/- 32 ng/ml. The IGF-II level was 282 +/- 84 ng/ml for infants and 687 +/- 169 ng/ml for adults. Both IGF-I and II levels in preterm infants were lower than those in term infants. IGF-I, and IGF-II, and SMPC levels showed a positive correlation with birth weight in term infants. Both IGF-I and IGF-II levels showed a strong positive correlation with gestational age in all infants.

Adult↗