bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of two potent calmodulin antagonists on calcium transport of brush border and basolateral vesicles from human duodenum
Authors: STOLL R. , STERN H. , RUPPIN H. , DOMSCHKE W. 
Published: July 2010

SUMMARYIn the present in‐vitro study we investigated the possible role of the calmodulin‐antagonistic drugs loperamide and calmidazolium in the regulation of transepithelial Ca2+ transport of human duodenum. Brush border membrane vesicles and basolateral membrane vesicles were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll‐gradient centrifugation method. Brush border and basolateral membrane vesicles were characterized using enzyme marker analysis and electron microscopy: alkaline phosphatase was enriched 20‐fold in brush border membrane vesicles, whereas [Na++ K+]‐stimulated adenosine triphosphatase was enriched 15‐fold in basolateral membrane vesicles. Calmodulin activity was determined by a specific radioimmunoassay after solubilizing brush border and basolateral membrane vesicles in 1% Triton X‐100. In basolateral membrane vesicles, we found no calmodulin activity. In brush border membrane vesicles calmodulin activity was impaired by 50% after pre‐incubation with loperamide or calmidazolium. We measured calcium, sodium, d‐glucose and d‐mannitol uptake with a rapid filtration technique. Before the transport experiments, brush border and basolateral membrane vesicles were pre‐incubated with 5 μM loperamide or 5 μM calmidazolium for 60 min at 5 °C. In drug‐pretreated, brush border membrane vesicles calcium uptake was signficantly reduced after 1 min incubation (– 25%±5%, P < 0.05); this effect was completely reversed in the presence of 5 μM calmodulin. In basolateral membrane vesicles, we found two Ca2+ transport systems: (1) Na+/Ca2+ exchange and (2) ATP‐dependent Ca2+ transport. In basolateral membrane vesicles loperamide had no effect. Calmidazolium had no effect on Na+/Ca2+ exchange, but significantly inhibited ATP‐dependent Ca2+ transport. This effect could not be reversed by calmodulin.
Review: acute human models of gastric mucosal injury
Authors: HAWKEY C. J. 
Published: July 2010

SUMMARYThe use of acute human models of gastric mucosal injury has been stimulated by a need to understand more fully the problems of non‐steroidal anti‐inflammatory drugs but such models have other applications. None is ideal and they all share certain drawbacks. For none of them has a precise relationship to clinical events been established and they have all tended to be employed on a population of young healthy subjects who are not those at greatest clinical risk. Of individual methods mucosal potential difference is an indirect measure which is too often affected by other influences to be acceptable as a measure of mucosal injury when used alone, although it has some value as an adjunct to other measurements. Assay of DNA in gastric washings is a suitable technique for quantifying desquamation of gastric epithelial cells occurring in response to acute injury; on present evidence its significance is much more difficult to assess in the context of continuing challenge over several days. By contrast, measurement of microbleeding is more suitable for quantifying injury over several days of NSAID ingestion; little bleeding is recorded with a single acute challenge. Endoscopy can demonstrate macroscopic lesions which result from mucosal injury—injury which is quantified more easily and sensitively by measurements of cellular exfoliation or bleeding. Paradoxically, endoscopy's strength has been to underline the scientific weakness of acute models because it shows that it is rare for ulcers, which are the lesions of clinical concern to develop in these studies.
Does Caved‐S decrease the gastric ulcer relapse rate during maintenance treatment with ranitidine?
Authors: MORGAN A. G. , PACSOO C. , TAYLOR P. , McADAM W. A. F. 
Published: July 2010

SUMMARYNinety‐five patients with healed gastric ulcers were treated with ranitidine 150 mg at night plus either Caved‐S two tablets twice daily, or an identical placebo preparation. Treatment was continued for 2 years: the recurrence rate after 1 year was 12.5% for single therapy and 19% for combined therapy, and 30 and 40% respectively after 2 years (differences not significant). No serious side‐effects were encountered, but patients found the combination therapy difficult to take, and it conferred no clinical advantage. In a 3 month follow‐up after stopping maintenance therapy, 11% of the patients had a symptomatic ulcer recurrence. It is therefore recommended that elderly patients with gastric ulceration should remain on maintenance therapy for life.
Effect of nicardipine on gastric acid secretion in man
Authors: PRIOR A. , WHORWELL P. J. 
Published: July 2010

SUMMARYThe effect of nicardipine on basal and pentagastrin‐stimulated gastric acid secretion in normal volunteers was investigated. When compared with saline, an intravenous infusion of nicardipine caused a significant decrease in peak acid output (from 37.8 mmol hour−1 to 28.8 mmol hour−1; P= 0.04) and a small reduction in aspirate volume. Nicardipine had no significant action on basal acid output or volume of aspirate. Proteolytic activity in both the basal and stimulated periods was unaffected by nicardipine as were serum gastrin concentrations. Although calcium channel blocking agents are theoretically antisecretory the present study suggests they are unlikely to have clinically useful therapeutic actions.
What is an intractable duodenal ulcer and how should it be managed?
Authors: POUNDER R. E. 
Published: July 2010

SUMMARYAn intractable duodenal ulcer is an ulcer that has not healed after 8 weeks of full‐dose treatment with a modern antiulcer drug. Such ulcers are relatively rare ‐ perhaps five in 100 patients will have intractable duodenal ulceration. The differential diagnosis includes non‐compliance as a cause of continuing ulceration, hypersecretion of gastric acid or other rare causes of ulcers in the duodenum. Investigations should include biopsy of the continuing ulceration at endoscopy, measurement of fasting plasma gastrin and routine haematology and biochemistry profiles. An intractable duodenal ulcer can be treated either by using a powerful antisecretory regimen (high doses of ranitidine or famotidine or a conventional dose of omeprazole), by changing to tripotassium dicitrato bismuthate or, in exceptional circumstances, by extremely careful surgical intervention.
What are the differences between the H2‐receptor antagonists?
Authors: SCHUNACK W. 
Published: July 2010

SUMMARYThe H2‐receptor antagonists which are used for ulcer therapy fall into four main structural classes. Cimetidine is an imidazole derivative; ranitidine belongs to the basically substituted furans, famotidine is a member of the guanidinothiazole group; and roxatidine belongs to the aminoalkylphenoxy series. Famotidine is the most potent, selective H2‐receptor antagonist yet available for ulcer therapy. On a weight basis, famotidine is approximately eight times more potent than ranitidine and 40 times more potent than cimetidine. Cimetidine, ranitidine and famotidine are competitive antagonists, while the long‐acting H2‐receptor antagonists, e.g. loxtidine and lamitidine, are insurmountable H2‐receptor blockers. Famotidine has a longer duration of action than either ranitidine or cimetidine. Because famotidine does not interact with cytochrome P‐450 of the hepatic enzyme system, it does not appear to affect the metabolism of drugs metabolized by this system. The overall number of side‐effects of the H2‐receptor antagonists is in the range of 2–3% and no irreversible adverse effects are known. Famotidine has been found to be generally well tolerated. In a first post‐marketing study, the number of patients with side‐effects was only 0.43%. Side‐effects such as headache, dizziness, constipation and diarrhoea have been observed only occasionally. Thus, famotidine is a safe and potent H2‐receptor blocker of acid secretion.
Lessons from prolonged gastric pH monitoring
Authors: BUMM R. , BLUM A. L. 
Published: July 2010

SUMMARYIntragastric pH monitoring has shown that the distribution of acidity within the stomach is not homogeneous. Not only is it affected by meals but it also has a circadian rhythm in which nocturnal pH falls to very acid levels in normal subjects. Although results of pH monitoring are highly reproducible within individuals, considerable inter‐individual variation has been shown. Duodenal ulcer patients do not appear to possess the normal buffering reaction to meals, but their night‐time acidity is within the normal range. In these patients, antacids and pirenzepine have a small acid‐neutralizing effect in the stomach; cimetidine is less potent than ranitidine and famotidine. Clinicians can choose between a single dose of either ranitidine or famotidine in the evening with dinner and a twice‐daily regimen.
Why are non‐steroidal anti‐inflammatory drugs important in peptic ulceration?
Authors: PORRO G. BIANCHI , PACE F. , CARUSO I. 
Published: July 2010

SUMMARYThe pathogenetic role of non‐steroidal anti‐inflammatory drugs (NSAIDs) in peptic ulcer disease is reviewed, on the basis of available experimental and epidemiological knowledge. In addition, original clinical data are provided concerning the prophylactic and therapeutic role of the H2‐receptor antagonists ranitidine and cimetidine, and colloidal bismuth subcitrate, in the treatment of NSAID‐associated peptic lesions in rheumatic patients.
A comparison of two ranitidine intravenous infusion regimens in critically ill patients
Authors: MARCHANT J. , SUMMERS K. , McISAAC R. L. , WOOD J. R. 
Published: July 2010

SUMMARYThe effect of two ranitidine intravenous infusion regimens on intragastric pH was studied in 134 critically ill patients admitted to 15 intensive care units. Intragastric pH was determined hourly for 30 hours. Those patients whose intragastric acidity fell below pH 4.0 for 3 or more of the first 6 hours were considered ‘at risk’ of developing stress‐related gastric lesions and randomized to receive a 50 mg bolus of ranitidine together with a continuous intravenous infusion of either 0.125 or 0.25 mg kg—1 h—1 ranitidine for 24 hours. The maximal elevation in intragastric pH was achieved within 12 hours. The median intragastric pH for the last 20 hours of the infusion period was 5.9 for the higher dose group and 5.6 for the lower dose group. The increase in intragastric pH achieved by the two dosage regimens did not differ significantly throughout the 24 hour period. Patients having two or more of five major risk factors (head injury, major trauma, sepsis, respiratory failure/insufficiency and major surgery) had better overall control of intragastric pH on the higher dose of ranitidine than those receiving the lower dose. The majority of intensive care patients are likely to receive satisfactory treatment with the lower dosage regimen that was tested (0.125 mg kg—1 h—1). Those with multiple risk factors may, however, require treatment with higher doses of ranitidine (0.25 mg kg—1 h—1).
Effect of enprostil on basal and meal‐stimulated gastric acid and pepsin secretion, serum gastrin and gastric emptying in healthy persons
Authors: BERSTAD K. , MASSEY H. , BERSTAD A. 
Published: July 2010

SUMMARYTen healthy volunteers took part in a double‐blind, randomized, crossover study of the effect of single doses of enprostil (70 μg) and placebo on basal and meal‐stimulated gastric acid, pepsin secretion and serum gastrin. Meal‐stimulation was induced by modified sham feeding combined with repeated gastric instillation and withdrawal of meat soup. When studied between 1 and 2.5 hours after oral administration of the drug, enprostil decreased basal acid output by 92% (P < 0.001) and stimulated acid output by 70% (P < 0.001). Basal and stimulated volumes of gastric juice were decreased by 50% (P < 0.02) and 35% (P < 0.002), respectively. Enprostil decreased stimulated pepsin output by 34% (P < 0.05), but had no effect on the concentration of pepsin. Neither basal nor stimulated serum gastrin concentrations were affected by enprostil. Percent recovery of the meal was measured by an unabsorbable marker, polyethylene glycol, instilled into the stomach mixed with the soup. Polyethylene glycol recovery decreased from 89% with placebo to 67% with enprostil (P < 0.01), indicating an enhanced gastric emptying rate with enprostil.
Pharmacological response to cimetidine and healing of duodenal ulceration: effects of highdose cimetidine and combination of cimetidine with pirenzepine
Authors: DEAKIN M. , COLIN‐JONES D. G. , WILLIAMS J. G. 
Published: July 2010

SUMMARYOvernight gastric secretion was studied in 32 patients with acute duodenal ulcers before treatment and whilst taking cimetidine 400 mg b.d. After 6 weeks of treatment with cimetidine 400 mg b.d. 13 patients had healed ulcers, seven patients had healed ulcers but a persistent erosive duodenitis, and 12 patients had persisting ulceration. Inhibition of nocturnal gastric secretion by cimetidine 400 mg b.d. was most profound in patients who healed their ulcers completely; a less profound inhibition of nocturnal gastric secretion was seen in the non‐healing and duodentis groups. In patients with persisting ulcers and poor inhibition of nocturnal gastric secretion by cimetidine, gastric secretion could be suppressed by either cimetidine 400 mg b.d. in combination with pirenzepine 50 mg b.d., or by cimetidine 1600 mg nocte, but suppression of nocturnal gastric secretion was more effective with cimetidine 1600 mg than cimetidine with pirenzepine.
Review: interactions between H2‐antagonists and non‐steroidal anti‐inflammatory drugs
Authors: HOWDEN C. W. 
Published: July 2010

SUMMARYNon‐steroidal anti‐inflammatory drugs (NSAIDs) are being prescribed increasingly with an H2‐antagonist. This article reviews those published studies which have examined the potential for pharmacokinetic and, where appropriate, pharmacodynamic interactions between these classes of drugs. Studies involving the administration of a single dose of a NSAID to young healthy volunteers are of limited relevance in establishing the likely effect of an H2‐antagonist on the blood concentrations of an NSAID in patients. Appropriate studies are those which will examine the effects of H2‐antagonists on the steady‐state pharmacokinetics of NSAIDs in patients with inflammatory joint diseases. More of such studies are required, particularly involving elderly patients.
The effect of four narcotics on cholecystokinin octapeptide stimulated gallbladder contraction
Authors: HAHN M. , BAKER R. , SULLIVAN S. 
Published: July 2010

SUMMARYIn an attempt to find the ideal analgesic to treat biliary tract pain we compared the effects of saline and equianalgesic doses of morphine, pentazocine, pethidine, and butorphanol on CCK—OP stimulated gallbladder emptying in healthy volunteers. Morphine produced a profound delay in gallbladder emptying while the other narcotics produced a significant delay in comparison to saline, but less than morphine. None of the drugs affected common bile duct diameter, bilirubin, liver enzymes or amylase. We recommend avoiding the use of morphine in the treatment of biliary and pancreatic pain, but although pethidine, pentazocine and butorphanol may be potentially detrimental we could find no definite superiority of one versus the others.
The effect of nicotine on the delay of gastric emptying
Authors: GRITZ E. R. , IPPOLITI A. , JARVIK M. E. , ROSE J. E. , SHIFFMAN S. , HARRISON A. , VUNAKIS H. VAN 
Published: July 2010

SUMMARYThe effect of cigarette smoking and its active component, nicotine, on the gastric emptying of solid food was assessed in a randomized double‐blind crossover design. Ten regular smokers were studied after a 6 h fast and least 18 h after their last cigarette. Subjects smoked a total of three high (1.91 mg) or low (0.17 mg) nicotine cigarettes, before and after a technetium‐labelled solid meal and were scanned by gamma camera periodically over a 2‐h period. All calculations of gastric emptying revealed a significant delay after smoking highversuslow nicotine cigarettes in: mean per cent isotope remaining in the stomach at each measurement point from 90–120 min; amount of meal remaining in the stomach at 2 h; and mean time at which 50% of the meal had emptied (T1/2). Delay in gastric emptying was significantly correlated with increase in serum nicotine concentration on the high nicotine day.
Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5‐aminosalicylic acid
Authors: NIELSEN O. H. , VERSPAGET H. W. , ELMGREEN J. 
Published: July 2010

SUMMARYPurified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5‐aminosalicylic acid (5‐ASA), and the 5‐ASA metabolite N‐acetylated‐5‐ASA (ac‐5‐ASA)) was tested at therapeutic colonic concentrations of 0.01–10 mm. Leukotriene B4 at a dose of 10 nm was equipotent with casein (5 g litre—1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5‐ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mm, respectively. These concentrations are below the lowest concentration of 5—ASA (2 mm) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.
Dose—response effect of famotidine on patterns of gastro‐oesophageal reflux
Authors: ORR W. C. , ROBINSON M. G. , HUMPHRIES T. J. , ANTONELLO J. , CAGLIOLA A. 
Published: July 2010

SUMMARYThe present study attempts to assess the alteration in patterns of gastro‐oesophageal reflux as assessed by 24‐h oesophageal pH monitoring by varying degrees of H2‐receptor blockade with famotidine. Subjects were 12 patients with complaints of daily heartburn who demonstrated at least 6% of acid mucosal contact time by 24‐h ambulatory oesophageal pH monitoring. All subjects had a positive Bernstein test, and nine of the 12 subjects had erosive oesophagitis. The study was conducted as a double‐blind crossover design utilizing 40 mg nocte, 20 mg b.d., and 40 mg b.d. and placebo treatments. Results indicated that all treatments significantly reduced the 24‐h percentage acid contact time (P < 0.05) compared to placebo. The two b.d. treatment regimens also significantly (P < 0.05) reduced the number of episodes lasting longer than 5 min. Only the b.d. regimens successfully lowered the percentage of upright acid exposure. All treatments significantly (P < 0.01) reduced the percentage of supine acid contact time, as well as the number of episodes lasting more than 5 min. It is concluded that gastro‐oesophageal reflux disease may well require a b.d. dosing regimen with farnotidine in order to achieve optimal mucosal healing and day time symptom control.
Successful treatment of a VIPoma by continuous subcutaneous infusion of somatostatin analogue (SMS 201‐995)
Authors: NIITSU Y. , GOTO Y. , MAEDA M. , TSUSHIMA N. , WATANABE N. , KOHGO Y. , URUSHIZAKI I. 
Published: July 2010

SUMMARYA case with WDHA syndrome due to VIPoma is reported. Injection of somatostatin analogue SMS 201‐995 was followed by prompt suppression of vasoactive intestinal polypeptide levels (VIP), decreased stool volume, and restoration of the serum potassium concentration to normal. Long‐term treatment with SMS 201‐995 for up to 20 weeks produced excellent clinical control and a decrease in tumour size. No adverse effects were noted except for localized pain at the site of injection. This was overcome by using a continuous subcutaneous infusion pump which also enabled the effective daily dosage to be reduced and thereby adverse reactions to be avoided.
No correlation between indomethacin‐induced gastroduodenal damage and inhibition of gastric prostanoid synthesis
Authors: GOLDIN E. , STALNIKOWICZ R. , WENGROWER D. , ELIAKIM R. , FICH A. , LIGUMSKY M. , KARMELI F. , RACHMILEWITZ D. 
Published: July 2010

SUMMARYThe effect of 1 week of treatment with indomethacin 150 mg/day on human gastric prostanoid synthesis was correlated with its effect on gastric and duodenal mucosa. Before and following 1 week of treatment, endoscopic appearance of the mucosa was evaluated and scored. Following 1 week of treatment with indomethacin, antral PGE2 and 6‐keto‐PGF1α were significantly lower than in normal subjects, but similar in patients with significant or with no mucosal damage. Co‐treatment with ranitidine 150 mg b.d. or with cimetidine 400 mg b.d. reduced the mean mucosal damage score but did not affect gastric prostanoid synthesis, which was similar irrespective of the presence or absence of mucosal damage. It is therefore suggested that there is no correlation between indomethacin‐induced inhibition of gastric prostanoid synthesis and its induction of mucosal damage.
Comparative irritancy of oxaprozin on the gastrointestinal tract of rats and mice: relationship to drug uptake and effects in vivo on eicosanoid metabolism
Authors: RAINSFORD K. D. 
Published: July 2010

SUMMARYStudies were performed in rats and mice to investigate the mechanisms of the comparatively low irritancy in the gastrointestinal (GI) tract of oxaprozin, relative to that of other non‐steroidal anti‐inflammatory drugs. A single dose of oxaprozin (100 mg/kg), given orally to rats, reduced the concentration of prostaglandin E2, but did not produce any gastric lesions or mucosal irritation, either visibly or when the mucosa was examined by scanning or transmission electronmicroscopy. The low gastric irritancy was reflected by lower concentrations of the drug in the gastric mucosa, compared with those in the upper intestinal tract, following oral administration of 100 mg/kg of [14C]oxaprozin. This distribution of the drug in the gastrointestinal tract reflected the absence of gastric irritancy when the drug was given repeatedly for 5 days by the oral route to rats. It was only after intraperitoneal administration of high doses of the drug that intestinal ulcers and peritonitis became evident, and then no gastric irritancy was observed. As with other non‐steroidal anti‐inflammatory drugs, there was some, but appreciably less, enhancement of gastric irritancy observed when the drug was given to mice treated with the cholinomimetic, bethanechol chloride (to enhance secretion of acid and pepsin). It is suggested that the inhibition of mucosal prostaglandin production by oxaprozin may be considered a ‘priming’ reaction, and that subsequent enhancement of irritancy occurs by stimulation of acid and pepsin. Structure—activity relationships of oxaprozin analogues were studied. The addition of electron‐withdrawing substituents, which markedly enhance the gastric ulcerogenic effects of other non‐steroidal anti‐inflammatory drugs, only slightly enhanced the irritancy of oxaprozin, thus providing further evidence for the inherent low ulcerogenicity of this molecule.