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Biomedical subjects

A Bennett

Publications and source records attributed to A Bennett.

At least 19 recordsLinked to original sources
PubMed1992

Methotrexate alters the fatty acid composition of NC adenocarcinoma cells in culture.

The effects of methotrexate and indomethacin alone and in combination have been examined on the fatty acid (FA) composition of total cellular lipids in cultured NC adenocarcinoma cells. These studies show that methotrexate can alter the lipid content of cancer cells. Methotrexate 16 ng/ml incubated with NC cells for 2 days increased the content of various FAs. When used alone, indomethacin 1 microgram/ml or methotrexate 8 ng/ml had no significant effect, but in combination caused FA increases, usually to about the same extent as with the higher concentration of methotrexate alone. No FA changes were seen up to 3 h with these drug concentrations or with methotrexate up to 10 micrograms/ml alone or with INDO 1 microgram/ml. These effects may explain previous findings that indomethacin potentiates methotrexate, an interaction which may be important in cancer therapy.

Animals↗
PubMed1992

Changes in tissue fatty acid composition in murine malignancy and following anticancer therapy.

We studied the mouse NC tumour, a subcutaneously transplanted adenocarcinoma originally of mammary origin. Measurements per g tissue were made of 17 fatty acids (FAs), the combined amounts of n-3, n-6, saturated, unsaturated, and total FAs, and of various FA ratios in the tumour, mammary tissue, spleen, liver and plasma. Compared with mammary tissue from normal mice, tumours of vehicle-treated controls had less of seven of the FAs and more of two FAs. Mice bearing the NC tumour often had changed (usually decreased) amounts of FAs in the 'normal' spleen, liver and plasma, but not in mammary tissue. Treatment with methotrexate (MTX) was studied alone and with indomethacin which can potentiate MTX cytotoxicity. Indomethacin 1.25 mg kg-1 (INDO) increased the amounts of 3/17 tumours FAs and the unsaturated FAs, but reduced 9/17 FAs, the saturated and the unsaturated FAs in 'normal' mammary tissue, and usually had no effect on the FAs of other tissues. MTX 2 or 4 mg kg-1 (MTX 2 or 4 mg) +/- INDO in general partly restored (increased) the amounts of tumour FAs, and reduced the saturated/unsaturated FA ratio. In the 'normal' spleen and plasma also, but not in the liver, MTX 2 mg generally somewhat restored the FA composition. However, as in the liver, the spleen 20:4 and 22:6 (which form prostaglandins and lipid peroxides) did not increase in the presence of INDO. With MTX 4 mg, some of the plasma and liver FAs decreased, in contrast to the tumour. There was generally no evidence of MTX potentiation by INDO. These results are discussed in relation to carcinogenesis, cachexia, and the response to treatment.

Animals↗
PubMed1992

A pharmacokinetic study of sulphasalazine and two new formulations of mesalazine.

We have examined the pharmacokinetics of enteric coated sulphasalazine compared with two new formulations of mesalazine. These consisted of microgranules of mesalazine coated with Eudragit S in a concentration of either 20 or 25% dry lacquer substance; these in turn were enclosed in capsules coated with Eudragit L. In-vitro dissolution studies of coated microgranules showed that drug release was pH dependent. Studies in 7 normal volunteers showed median peak concentrations of 5-amino-salicylic acid and N-acetyl-5-amino-salicylic acid occurred at about 6 hours with both microgranular preparations, compared with sulphasalazine at 15 h. The microgranule formulation coated with 20% Eudragit S gave serum levels and overall systemic absorption similar to values with sulphasalazine. This new formulation may be of value for delivering mesalazine and other therapeutic agents to the colon.

Adult↗
PubMed1992

Effects of cupric chloride and tamrabhasma, a traditional Indian preparation of copper, on eicosanoid production by human gastric and colonic mucosa.

Tamrabhasma is a traditional copper oxide-containing Indian preparation which has anti-ulcer activity. We have studied the effect of tamrabhasma and CuCl2.2H2O on prostaglandin formation by human gastric and colonic mucosa and submucosa, as prostaglandins have mucosal protective activity, and their release may contribute to the anti-ulcer effect. With the gastric mucosa, tamrabhasma 10 micrograms mL-1, but not 0.1 or 1 microgram mL-1, increased prostaglandin E (PGE) concentration by 38% (P < 0.05), with little or no effect on 6-keto-PGF1 alpha, thromboxane B2 or the leukotriene (LT) LTC4/LTD4. CuCl2.2H2O (10 micrograms mL-1) increased 6-keto-PGF1 alpha by 46% (P < 0.05), but 0.1, 1, 50 and 250 micrograms mL-1 did not significantly affect any of the prostanoids, and only the highest concentration reduced the amount of LTC4/LTD4. In the colon mucosa, tamrabhasma (0.1-10 micrograms mL-1) or CuCl2.2H2O (10-50 micrograms mL-1) increased all the prostanoids and this effect was greater than in the gastric mucosa but there was no significant change in LTC4/LTD4. CuCl2.2H2O showed a bell-shaped concentration-effect curve, with no significant effect at lower and higher amounts. Indomethacin (0.1-10 micrograms mL-1) caused a concentration-dependent reduction in the prostanoid amounts. The effect of tamrabhasma was probably not only due to the presence of Cu2+, as tamrabhasma was more effective than CuCl2.2H2O alone; in addition the solubility of CuO is very low. Increased prostanoid levels might explain, at least partly, the gastric mucosal protection by tamrabhasma. The results in the colon, however, raise the possibility that tamrabhasma should be examined for the treatment of inflammatory bowel disease.

Anti-Ulcer Agents↗
PubMed1992

PAF formation by human gastrointestinal mucosa/submucosa in-vitro: release by ricinoleic acid, and inhibition by 5-aminosalicylic acid.

Human isolated gastrointestinal mucosa/submucosa incubated with ricinoleic acid (12.5-100 micrograms mL-1) or the calcium ionophore A23187 (10 micrograms mL-1) released platelet-activating factor (PAF) as determined by a scintillation proximity assay after extraction and purification. 5-Aminosalicylic acid (25-100 micrograms mL-1) inhibited PAF release by ricinoleic acid in a concentration-dependent manner, and 50 micrograms mL-1 reduced the effect of A23187. We suggest that PAF may play a role in the laxation and mucosal damage by ricinoleic acid released from castor oil.

Aminosalicylic Acids↗
PubMed1992

The effects of various peptides on human isolated gut muscle.

The effects of eleven peptides of gastrointestinal origin have been studied on the contraction, relaxation and spontaneous activity of circular and longitudinal muscle strips from different regions of the human gastrointestinal tract. The effects varied with the peptides and sometimes with the region and muscle layer. There was either contraction, no effect, or relaxation and/or inhibition of an acetylcholine-induced contraction. Responses to some peptides are consistent with the possibility that they may contribute directly to the control of motility: galanin, neurotensin and substance P might be involved in contraction, and vasoactive intestinal peptide, peptide histidine isoleucine and peptide histidine methionine might be inhibitory transmitters.

Acetylcholine↗
PubMed1991

Loading-related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: a role for prostacyclin in adaptive bone remodeling?

Cyclic mechanical loading sufficient to engender strains of physiologic magnitude applied to recently excised canine cancellous bone cores in vitro increased the release of prostaglandin E (PGE) and prostacyclin (PGI2, measured as its breakdown product 6-keto-PGF1 alpha), during a 15 minute loading period in which PG levels were measured in perfusing medium at 5 minute intervals. Peak production occurred in the 0-5 minute sample. Mean levels preload compared to during load were PGE, 2.66 and 3.67 ng/ml (p less than 0.002); and 6-keto-PGF1 alpha, 543 and 868 pg/ml (p less than 0.007). The elevated levels then declined to preload levels during the loading period. However, the 5-10 minute but not the 10-15 minute samples still contained levels greater than preload values. A second 15 minute period of load, 1 h following the end of the first, produced smaller increases in the levels of release that were statistically significant only for the first 0-5 minute sample during load (preload compared to load mean values, PGE, 1.09-1.66 ng/ml, p less than 0.02; 6-keto-PGF1 alpha, 401-558 pg/ml, p less than 0.04). Immunolocalization revealed PGE and 6-keto-PGF1 alpha in lining cells and 6-keto-PGF1 alpha but not PGE in osteocytes. Addition to the medium of 1 microM PGE2, approximating the concentration produced by loading, had no significant effect on the specific activity of the extractable RNA fraction labeled with [3H]uridine, whereas 1 microM PGI2 produced an increase similar to that seen previously with loading.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Mesalazine release from coated tablets: effect of dietary fibre.

Delayed-release mesalazine formulations relay on pH-dependent coat dissolution to ensure delivery of 5-aminosalicylic acid (5-ASA) to the colon. As dietary fibre acidifies the colonic lumen we have studied the effect of fibre supplementation in 10 patients with quiescent colitis. Greater intake of dietary fibre was associated with a decrease in stool pH and an increase in stool frequency and faecal mass. However, the 24 h faecal and urinary excretion of 5-ASA and N-acetyl-5-ASA was unchanged. The percentage of total faecal ASA excreted as N-acetyl-5-ASA correlated with whole-gut transit time, suggesting that prolonged transit may be disadvantageous to patients with colitis as N-acetyl-5-ASA appears to be inactive.

Adult↗
PubMed1991

Self-reported long-term outcomes of hysterectomy.

OBJECTIVES: To investigate women's perceptions of and satisfaction with the long-term outcomes from a hysterectomy performed between 2 and 10 years ago and to determine whether satisfaction is related to demographic factors, factors associated with the hysterectomy, and the number or type of perceived benefits and problems associated with the hysterectomy. DESIGN: Retrospective survey by telephone interview and postal questionnaire of 236 women who had a hysterectomy between 2 and 10 years ago. SETTING: Women who had had a hysterectomy were identified from a community survey in the Hunter Region of NSW, Australia. SUBJECTS: Two hundred and thirty-six women who self-reported having had a hysterectomy between 2 and 10 years ago. MAIN OUTCOME MEASURES: Perceived benefits resulting from the hysterectomy; perceived physical and psychological problems caused by the hysterectomy; satisfaction with care. RESULTS: Relief from heavy bleeding was the most frequent benefit (57%) and the most important benefit (32%). Most of the women reported improvements in symptoms experienced before hysterectomy but more than half the women had symptoms which they believed had been worsened or caused by the hysterectomy. Despite this, high levels of satisfaction with the operation were reported. CONCLUSION: The results highlight the need to examine more closely decision-making about treatment for menstrual symptoms such as heavy bleeding.

Adult↗
PubMed1991

Studies of three non-peptide cholecystokinin antagonists (devazepide, lorglumide and loxiglumide) in human isolated alimentary muscle and guinea-pig ileum.

1. Three recently described non-peptide cholecystokinin (CCK) antagonists (devazepide, lorglumide, loxiglumide) have been studied for their antagonism of the contraction to cholecystokinin-octapeptide (CCK-OP) in human alimentary muscle and guinea-pig intestine. 2. Each antagonist caused a concentration-dependent inhibition of the contraction induced by CCK-OP, regardless of regional and species differences. 3. The potencies of each drug, estimated by use of an adaptation of the Cheng & Prusoff equation, were similar in the different regions of human alimentary tract (weighted mean apparent pKB, +/- s.e. mean: devazepide, 5.76 +/- 0.08, n = 20; lorglumide, 5.82 +/- 0.04, n = 25; loxiglumide, 5.87 +/- 0.07, n = 24). 4. In contrast, the potencies differed markedly in the guinea-pig ileum. Apparent pKB values obtained by the same method as with human tissues were, mean +/- s.e.mean: devazepide, 10.61 +/- 0.61; lorglumide, 7.43 +/- 0.20; loxiglumide, 6.67 +/- 0.12. pKB values obtained from classical competition experiments were: devazepide, 10.09 +/- 0.09; lorglumide 7.70 +/- 0.12; loxiglumide 6.08 +/- 0.22. 5. The CCK receptors in human gut muscle from different regions seem to be similar, but there appear to be species differences.

Animals↗
PubMed1991

The effect of nifedipine alone or combined with cytotoxic chemotherapy on the mouse NC carcinoma in-vitro and in-vivo.

Effects of the calcium antagonist nifedipine on the response of the murine NC carcinoma has been examined alone and together with cytotoxic chemotherapy in-vitro and in-vivo. The cytotoxic drug combination of methotrexate and melphalan, or nifedipine alone (0.2-25 micrograms mL-1), caused a concentration-related reduction of NC cell growth in culture. At the lower concentrations, combination to the cytotoxic drugs with nifedipine resulted in an addition of the separate drug effects, but with drug concentrations that on their own approached maximal effectiveness the combined response was less than additive. NC tumours were excised from mice 14 days after inoculation s.c. with NC cells, weighed, and extracted for prostanoids. Mouse survival was determined up to day 121, and cancer spread was recorded postmortem. Nifedipine 1, 5 or 10 mg kg-1 had little or no effect on the tumour weight, tumour prostanoid content, metastasis to the lymph nodes or lungs, or on the increase of mouse longevity by the cytotoxic drugs.

Animals↗
PubMed1991

Release of platelet-activating factor (PAF) from human colon mucosa and its inhibition by 5-aminosalicylic acid.

Tissues from 6 operation specimens were incubated at 37 degrees C for 30 min +/- ricinoleic acid 6.25-100 micrograms/ml. PAF was determined in the incubates by scintillation proximity assay (Amersham) after extraction and purification. No PAF was detected in control samples (less than 0.4 ng/g/30 min), whereas ricinoleic acid 12.5-100 micrograms/ml stimulated PAF output (18.3 +/- 2.1 ng/g/30 min, mean +/- sem). 5-ASA 25-100 micrograms/ml caused a 5-100% inhibition of the PAF release by 50 micrograms/ml ricinoleic acid. The authors conclude that PAF can be released by damage to human colonic mucosa/submucosa, and that the inhibition of PAF release in ulcerative colitis may at least partly explain the therapeutic effect of 5-ASA.

Aminosalicylic Acids↗
PubMed1990

Parathyroid hormone, but not prostaglandin E2, changes the shape of osteoblasts maintained on bone in vitro.

Parietal bones from 2-week-old rats were dissected free from the sutural regions, dura mater, and periosteum, leaving the surface covered with osteoblasts and some osteoclasts. Prostaglandin (PG) production by these "stripped" bones under basal conditions and after exposure to parathyroid hormone (PTH) was measured by radioimmunoassay of the culture medium (minimum essential medium with or without added 10% heat-inactivated fetal calf serum). Cultured specimens were examined by scanning electron microscopy for changes in osteoblast length, orientation, ruffling, and overlap. As demonstrated previously, PTH caused the osteoblasts to elongate, align, and show fewer ruffles compared to controls. PTH increased PG synthesis by the stripped bones. Indomethacin inhibited PG formation but did not affect the osteoblast shape change. PGE2, indomethacin, or both drugs together had no discernible effect on any morphologic features. These findings indicate that PGE2 does not change osteoblast shape and that the cell shape change with PTH is not mediated by endogenous prostanoids.

Animals↗
PubMed1990

The effects of cholecystokinin octapeptide on human isolated alimentary muscle.

1. We studied cholecystokinin octapeptide (CCK-OP) for its motor effects and sites of action on human isolated muscle from stomach, small intestine and colon. 2. CCK-OP induced a concentration-dependent contraction of all the longitudinal muscles and of circular muscle from the stomach and large intestine. The peptide acted directly on these muscles at a site not involving muscarinic receptors. 3. CCK-OP relaxed the circular muscle of the small intestine and/or reduced the contractions to acetylcholine, by stimulating intramural postganglionic inhibitory neurones.

Acetylcholine↗
PubMed1990

Effect of ethanol on eicosanoid synthesis by human gastric and colonic mucosal pieces.

1. Human gastric and colonic mucosa obtained at operation was cut into small pieces and incubated with different concentrations of ethanol. 2. Ethanol (5-40%) caused a concentration-dependent increase in the amounts of prostaglandin E (PGE), thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and (up to 20% ethanol) leukotriene C4/D4 (LTC4/D4) in incubates of mucosal pieces from either region. 3. Higher concentrations of ethanol usually caused small increases or reductions of eicosanoid levels; gastric mucosal PGE and 6-keto-PGF1 alpha were still increased by 100% ethanol, whereas TXB2 was unaltered, and LTC4/D4 was reduced. With the colonic mucosa, 100% ethanol increased PGE but reduced the other eicosanoids. 4. Gastric mucosal pieces incubated in water or phosphate buffer yielded generally similar amounts of eicosanoids. However, colonic mucosa yielded more when incubated in water, possibly indicating a greater sensitivity to osmotic damage. This difference between the two regions is consistent with the ability of the gastric mucosa to resist damage by water on its epithelial surface.

6-Ketoprostaglandin F1 alpha↗