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Biomedical subjects

J Hardcastle

Publications and source records attributed to J Hardcastle.

At least 55 records · Page 3Linked to original sources
PubMed1990

The effect of loperamide oxide on prostaglandin-stimulated fluid transport in rat small intestine.

The effects of loperamide and loperamide oxide on basal and prostaglandin E2-stimulated fluid transport by rat small intestine have been investigated. In contrast to loperamide, loperamide oxide, when applied intraperitoneally, failed to inhibit either basal or prostaglandin E2-stimulated fluid transport. However, intraperitoneal administration of loperamide oxide following its incubation with the contents of the intestinal lumen under aerobic conditions resulted in an effective inhibition of fluid secretion. The activating material was present in the essentially non-particulate 3000 g supernatant fraction of the luminal contents and was heat-stable.

Animals↗
PubMed1990

Enhanced intestinal glucose and alanine transport in cystic fibrosis.

The rise in short-circuit current associated with the active transport of glucose and alanine was measured in intestinal biopsy samples from children with cystic fibrosis. The glucose-induced increase in the short-circuit current was greater in the cystic fibrosis tissues than in control samples over the whole range of concentrations tested (2.5-35 mM), a reflection of an increased maximum rate of transport. Similar results were obtained with alanine. These findings suggest that active Na(+)-linked nutrient transport is enhanced in cystic fibrosis.

Adolescent↗
PubMed1990

New diagnostic method for cystic fibrosis.

We report 3 cases where the diagnosis of cystic fibrosis (CF) was either confirmed or refuted by studies of chloride secretion in intestinal mucosal biopsies. In one case a heterozygous state was indicated and later confirmed by gene probe studies. The technique clearly distinguishes between CF and control patients and can provide a rapid diagnosis even in the neonatal period.

Child, Preschool↗
PubMed1990

Intestinal transport in cystic fibrosis (CF).

Ion transport was measured in jejunal biopsies using short-circuit current (SCC) as an index of net electrogenic ion transport. Increases in SCC associated with stimulation of Cl- secretion were observed in control tissues, but CF tissues did not exhibit such a response, indicating a failure of intestinal Cl- secretion. The rise in SCC associated with Na(+)-linked glucose absorption was greater in CF tissues than in controls, reflecting an enhanced active absorption of glucose.

Biological Transport, Active↗
PubMed1989

Screening for colorectal cancer.

In this study, testing the faeces for occult blood with the Haemoccult test was well accepted by patients. Although this helped to identify those patients whose symptoms needed investigation and led to quicker diagnosis of colorectal neoplasia, the pathological staging was not improved.

Adult↗
PubMed1989

Abnormal jejunal potential difference in cystic fibrosis.

Transmucosal potential difference (PD) and intraluminal pressure were recorded from the same jejunal site in 15 healthy adult controls and 4 adults with cystic fibrosis. In the controls, runs of contractions were associated with wave-like changes in PD with, during phase III-like activity, a mean peak amplitude of -9.7 mV. Although there were no obvious differences in motor patterns, wave-like changes in PD were absent in patients with cystic fibrosis. Intraluminal boluses of 4 mg pilocarpine, or 0.1 mg prostaglandin E2, caused changes of -4.6 mV and -4.5 mV, respectively, in controls; these responses were not seen in patients with cystic fibrosis. There were no significant differences in basal PD and PD changes caused by altered concentrations of infused saline or glucose between patients and controls.

Action Potentials↗
PubMed1989

Effect of auranofin on ion transport by rat small intestine.

Auranofin, applied either mucosally or serosally, increased the potential difference and short-circuit current generated by stripped sheets of rat mid-intestine in a concentration-dependent manner. In-vivo auranofin induced a net fluid secretion, suggesting that the rise in electrical activity represented a stimulation of anion secretion. Removal of chloride or addition of frusemide inhibited the auranofin-induced increase in short-circuit current, indicating that chloride was the anion involved and in the case of serosal auranofin this was confirmed by direct measurement of ion fluxes. The effects of both mucosal and serosal auranofin were calcium-dependent. The gold component of the auranofin molecule is probably responsible for its secretory actions as these were mimicked by chlorauric acid. The ability of auranofin to stimulate intestinal secretion may contribute to its diarrhoeagenic action.

Animals↗
PubMed1988

Involvement of prostaglandins in histamine-induced fluid and electrolyte secretion by rat colon.

Histamine increased the transmural potential difference across rat colon in-vivo and induced a net secretion of fluid. Both effects were inhibited by indomethacin. Histamine increased the potential difference and short-circuit current, and reduced tissue resistance in colonic sheets in-vitro. This response was reduced in the absence of chloride in the bathing medium or in the presence of serosal frusemide, suggesting that histamine stimulated electrogenic chloride secretion by the colon. The rise in short-circuit current induced by histamine was calcium-dependent since it was reduced in the absence of serosal calcium or in the presence of serosal verapamil. Indomethacin, a cyclo-oxygenase inhibitor, and mepacrine, a phospholipase inhibitor, both caused a dose-dependent inhibition of the electrical response of colonic sheets to histamine, without affecting the rise in short-circuit current induced by prostaglandin E2. The stimulation of chloride secretion induced by histamine in rat colon therefore appears to be mediated by an increased production of prostaglandins.

Animals↗
PubMed1988

The response of the intestinal mucosa to prostaglandin E2 during withdrawal from morphine.

Experiments were designed to determine whether the diarrhoea characteristic of morphine withdrawal results from an enhanced sensitivity of the intestinal mucosa to PGE2. Rats (250-300 g) were made morphine-dependent by subcutaneous injection of an emulsion releasing 300 mg morphine HCl over 48 h. In-vivo, the transintestinal potential difference (PD) responses to PGE2 (4.6-46 micrograms kg-1 i.v.), which reflect increased Cl secretion, were significantly larger in withdrawn (morphine emulsion, 10 mg kg-1 naloxone s.c.) compared with non-dependent animals (emulsion only, naloxone s.c., P less than 0.05). Muscle-stripped intestinal sheets from dependent animals incubated with naloxone (10(-5) mol L-1) in-vitro did not demonstrate a greater electrical response (PD, short circuit current) to PGE2 (1.4 x 10(-6) mol L-1) than sheets taken from non-dependent animals. In-vitro preparations from animals withdrawn in-vivo did not respond differently from tissue taken from non-dependent animals (naloxone 10 mg kg-1 s.c., 10(-4) mol L-1 in medium, in both groups). This occurred in whole sheets of intestine as well as sheets without attached muscle. Jejunal fluid absorption in-vivo was lower in withdrawn animals than in non-dependent animals. However, the responses to intra-arterial infusion of PGE2 were similar in both groups with 2 micrograms min-1 inhibiting absorption and 4 micrograms min-1 inducing secretion. In-vivo, PGE2-induced Cl secretion appears to be enhanced during withdrawal although net fluid transport is not altered, suggesting different effects of the withdrawal process on the electrogenic Cl secretory and neutral NaCl absorptive mechanisms.

Animals↗
PubMed1988

Failure to induce secretion in jejunal biopsies from children with cystic fibrosis.

The secretory activity of jejunal biopsies from children with cystic fibrosis (CF) has been investigated using a modified Ussing chamber technique. Samples from six children with CF failed to respond when challenged with the intestinal secretagogues acetylcholine (10(-3) M), prostaglandin E2 (1.4 X 10(-6) M) and dibutyryl cyclic AMP (10(-3) M), while control tissues exhibited rises in short circuit current of 28.1 (7.4) (6) microA/cm2, 23.4 (4.6) (6) microA/cm2 and 10.0 (2.0) (4) microA/cm2 respectively in response to these agents. The calcium ionophore, A23187 (3.8 X 10(-6) M), increased the short circuit current in all the control tissues (mean change = 10.1 (2.7) (5) microA/cm2) and induced a small response in some of the CF tissues. Both groups of tissues generated a rise in short circuit current associated with sodium linked glucose (10 mM/l) absorption (control = 32.6 (9.3) (6) microA/cm2, CF = 36.2 (13.9) (6) microA/cm2, p greater than 0.05). These results show that the defect in chloride transport observed in other epithelia in CF also exists in the jejunum and could contribute to the intestinal effects of the disease. The technique used should permit further studies of the basic defect and may be of diagnostic value.

Acetylcholine↗
PubMed1987

Auranofin inhibits the active uptake of bile acid by rat ileum.

Auranofin in the mucosal fluid inhibited the active Na+-dependent absorption of taurocholic acid by everted sacs of rat ileum. It did not however, affect the passive uptake of taurocholic acid by sacs of mid-intestine. The inhibition by auranofin of active bile acid absorption could result from its previously demonstrated ability to inhibit Na+, K+-ATPase activity. A reduction in the reabsorption of bile acids by the ileum may contribute to the diarrhoea experienced by some patients taking auranofin.

Animals↗
PubMed1987

The secretory actions of histamine in rat small intestine.

1. Histamine caused a dose-dependent rise in the transintestinal potential difference in vivo that was competitively blocked by H1, but not by H2 antagonists. This effect of histamine was also reduced by the cyclo-oxygenase inhibitor indomethacin. 2. Histamine induced a net secretion of fluid by the small intestine and this effect was reduced by indomethacin. 3. In intestinal sheets histamine increased the potential difference, short-circuit current and tissue resistance. This response was decreased in the absence of Cl- and in the presence of furosemide, suggesting that Cl- secretion was responsible for the observed electrical changes. This was confirmed by direct measurement of ion fluxes which showed an increase in net Cl- secretion together with an inhibition of net Na+ absorption. 4. The response to histamine was Ca2+-dependent since it was inhibited by removal of serosal Ca2+ and by verapamil. 5. Indomethacin caused a dose-dependent reduction in the response of intestinal sheets to histamine, without affecting the rise in short-circuit current induced by mucosal glucose or serosal prostaglandin E2. Mepacrine also inhibited the response to histamine, but not that to prostaglandin E2. 6. It is concluded that histamine induces intestinal secretion by stimulating the production of prostaglandins which then activate the secretory process.

Animals↗
PubMed1986

The effect of auranofin on the colonic transport of Na+ and fluid in the rat.

Auranofin in the mucosal fluid caused a dose-dependent inhibition of fluid and Na+ absorption by everted sacs of rat colon. Serosal auranofin was without effect. (Na+ + K+)ATPase activity of homogenates of mucosal scrapes of rat colon was inhibited by auranofin in a dose-related manner, while Mg2+-ATPase activity was little affected. These actions of the drug on colonic transport mechanisms could contribute to the diarrhoea associated with auranofin therapy.

Adenosine Triphosphatases↗
PubMed1986

The involvement of basolateral potassium channels in the intestinal response to secretagogues in the rat.

The possible involvement of basolateral K+ channels in the intestinal response to secretagogues was investigated using stripped sheets of rat mid-intestine. Increasing the serosal K+ concentration reduced the rise in short-circuit current induced by acetylcholine, 5-hydroxytryptamine, theophylline and prostaglandin E2 (PGE2) without affecting the change caused by glucose. The secretagogue-induced rise in short-circuit current was inhibited by quinine, but not by tetraethylammonium chloride, apamin or 3,4-diaminopyridine. Acetylcholine stimulated 86Rb efflux into the serosal fluid from pre-loaded intestinal sheets and a smaller response was observed with PGE2. The acetylcholine-induced stimulation of 86Rb efflux was inhibited by serosal quinine and lack of serosal Ca2+. Furosemide in the serosal fluid reduced the electrical response to acetylcholine without affecting the increase in 86Rb efflux. It is concluded that as well as increasing luminal Cl- permeability, intestinal secretagogues also enhance the basolateral K+ conductance by activating Ca2+-dependent K+ channels.

Acetylcholine↗
PubMed1986

Inhibitory actions of loperamide on absorptive processes in rat small intestine.

Mucosal loperamide caused a dose dependent reduction in the absorption of actively transported hexoses and amino acids, together with the associated rise in short circuit current. Na+ and fluid movement were also inhibited. Serosal application of the drug was without effect on these processes. The passive movement of fructose across the gut was not affected by loperamide which is therefore unlikely to act by reducing tissue permeability. In low Na+ conditions the inhibitory actions of loperamide on glycine absorption were reduced. Loperamide reduced basal Na+ transport although it did not affect the stimulation of Na+ absorption caused by mannose. Loperamide had no effect on the total ATPase activity nor on the Na+, K+-ATPase activity of mucosal homogenates. The effects of loperamide were not mimicked by morphine nor were they antagonised by naloxone and hence do not seem to involve an opiate receptor. It is concluded that loperamide exerts its inhibitory effects by an interaction with the Na+ sites of the nutrient carriers.

Animals↗