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Biomedical subjects

A Bennett

Publications and source records attributed to A Bennett.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1990

Smoking, eicosanoids and ulcerative colitis.

In this study, which is the first of its kind using normal tissue samples that are very difficult to obtain, we have investigated the hypothesis that smoking protects against ulcerative colitis by altering the colonic mucosal formation of prostaglandins and related substances. Colonic mucosa biopsied from healthy young men produced prostaglandin E, 6-keto-PGF1 alpha (formed from PGI2), leukotriene B4 and leukotriene C4/D4/E4 as determined by radioimmunoassay. With each substance, the median yield was lower in the group of smokers who smoked 3 cigarettes in the 2 h before biopsy, than in the non-smokers. However, with each eicosanoid the statistical probability approached only the 10% level, but the fact that the trend was the same for all eicosanoids somewhat strengthens the possibility of a real difference between the groups.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Polyphloretin phosphate (PPP) antagonists of prostaglandin action also inhibit prostaglandin biosynthesis in-vitro.

Several polyphloretin phosphate (PPP) fractions (low mol. wt LC1259; high mol. wt LC1261; crude mixture, LC101) were confirmed in their established property as antagonists of the pharmacological actions of prostaglandins in a preparation of guinea-pig isolated ileum stimulated by prostaglandin (PG)E2. Further samples of the same material were then compared in-vitro with indomethacin in their ability to inhibit prostaglandin biosynthesis from arachidonic acid by a microsomal enzyme preparation. All three PPP fractions potently inhibited prostaglandin generation, with the rank order of potency LC1259 = LC101 = indomethacin greater than LC1261. The oral LD50 in mice was 25 mg kg-1 for indomethacin and greater than 1 g kg-1 for LC101. PPP fractions (especially LC101) may therefore have therapeutic potential as anti-inflammatory agents.

Animals↗
PubMed1990

Effect of pirazolac on prostanoid synthesis by human gastric mucosa in vitro.

Pirazolac concentration-relatedly inhibited the accumulation of prostanoids in incubates of human gastric mucosa, but this inhibition was less than that by indomethacin and other commonly used non-steroidal anti-inflammatory drugs. This difference may explain the claim that pirazolac is less damaging to the stomach.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Breast cancer, prostaglandins and patient survival.

Prostaglandins may have both undesirable and desirable effects in malignant disease. Their possible roles in breast cancer were studied by examining the relationships between different variables and the amounts of prostaglandin-like material (PG-LM) extracted from 141 breast carcinomas. Univariate analysis indicates a direct correlation with patient age and menopausal status, with a greater yield from cancers of post- compared with pre-menopausal women. Tumours up to 2 cm diameter yielded more PG-LM than those measuring greater than 2-5 cm. Although there was also a direct correlation with bone metastasis near to the time of surgery, this was because no positive bone scans occurred in patients whose tumours yielded little total PG-LM (less than 16 ng PGE2 equivalents per g tissue). Since tumour PG-LM did not predict later spread to bone, and yields of greater than 16 ng g-1 were similar in the positive and negative bone scan groups, tumour PG-LM appears to be unimportant for skeletal metastasis. There was no obvious relationship of tumour PG-LM to the grade of malignancy, tumour type, amounts of fibrous tissue (and therefore malignant cells), invasion of blood vessels and lymphatics or presence of plasma cells. Multivariate analysis indicates that disease-free survival is longest with an intermediate production of tumour total PG-LM. Of the 82 patients now dead, the cause was attributed to metastatic disease in 69 cases. No relationship of PG-LM to the length of survival was seen with univariate or multivariate analysis. However, when just the post-menopausal patients who died within the first 3 postoperative years were analysed, there was a highly significant inverse correlation between the tumour total PG-LM and the time to death. The reason(s) for these different findings on overall survival compared with just the patients who died are not understood, but the results may indicate that one or more other variables must co-exist with a high tumour PG-LM to hasten death.

Bone Neoplasms↗