A study on the protease activity and structure of pepsin in the presence of atenolol and diltiazem.

Pepsin, as the main protease of the stomach, plays an important role in the digestion of food proteins into smaller peptides and performs about 20% of the digestive function. The role of pepsin in the development of gastrointestinal ulcers has also been studied for many years. Edible drugs that enter the body through the gastrointestinal tract will interact with this enzyme as one of the first targets. Continuous and long-term usage of some drugs will cause chronic contact of the drug with this protein, and as a result, the structure and function of pepsin may be affected. Therefore, the possible effect of atenolol and diltiazem on the structure and activity of pepsin was studied. The interaction of drugs with pepsin was evaluated using various experimental methods including UV-Visible spectroscopy, fluorescence spectroscopy, FTIR and enzymatic activity along with computational approaches. It was showed that after binding of atenolol and diltiazem to pepsin, the inherent fluorescence of the protein is quenched. Determination of the thermodynamic parameters of interactions between atenolol and diltiazem with pepsin indicates that the major forces in the formation of the protein-drug complexes are hydrophobic forces and also atenolol has a stronger protein bonding than diltiazem. Additional tests also show that the protease activity of pepsin, decreases and increases in the presence of atenolol and diltiazem, respectively. Investigation of the FTIR spectrum of the protein in the presence and absence of atenolol and diltiazem show that in the presence of atenolol the structure of protein has slightly changed. Molecular modeling studies, in agreement with the experimental results, confirm the binding of atenolol and diltiazem to the enzyme pepsin and show that the drugs are bind close to the active site of the enzyme. Finally, from experimental and computational results, it can be concluded that atenolol and diltiazem interact with the pepsin and change its structure and protease activity.

The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?

OBJECTIVES: During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non-acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this. METHODS: The role of Gaviscon Advance (GA), a raft-forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in-vitro models. KEY FINDINGS: GA was able to dose-dependently inhibit pepsin activity over and above the neutralisation effect of the formulation. This was evident against both protein and collagen substrates using two distinct colorimetric assays. GA was able to retard the diffusion of pepsin and multiple bile acids using a Franz cell model. Using the raft-forming mode of action GA was able to remove both pepsin and multiple bile acids from a simulated reflux event. There was capacity in the GA raft to accommodate aggressors from multiple reflux events. CONCLUSIONS: GA can specifically remove both pepsin and bile acids from the refluxate, limit their diffusion and affect enzymatic activity of pepsin. There is a role for GA to reduce the damaging potential of the refluxate and thus protect the oesophagus.

Secretion of total pepsin and pepsin 1 in healthy volunteers in response to pentagastrin and to insulin-induced hypoglycaemia.

OBJECTIVE: Human gastric juice contains a multiplicity of proteinases, and one enzyme (pepsin 1) is increased in patients with peptic ulcer disease. However, little is known about its secretion in health. The purpose of this study was to determine the pepsin 1 content in relation to the total pepsin of human gastric juice in healthy volunteers and the effect of different stimuli on secretion. MATERIAL AND METHODS: Human gastric juice from healthy volunteers was collected at 10-min intervals over a period of 30 min basally and up to 60 min after continuous intravenous pentagastrin administration (n=13) or insulin-induced hypoglycaemia (n=11). Pepsin 1 was measured by semiquantitative agar gel electrophoresis and the total pepsin as the proteolytic activity calibrated against pig pepsin A. RESULTS: Pepsin 1 was present in 23 out of 24 basal gastric juice samples at a mean concentration of approximately 12 microg/ml. During continuous intravenous pentagastrin to 11 subjects for 60 min, the mean concentration and secretion rates per minute rose to 24 microg/ml and 122 microg/min at 60 min; the proportion of pepsin 1 to total pepsin was 2.8% in basal secretions increasing to 7.8% in the 60 to 70-min samples. Following intravenous insulin administration to 11 subjects, the mean concentration and secretion rates of pepsin 1 rose to 33 microg/ml and 127 microg/min at 60 min: the proportion of pepsin 1 to total pepsin was 0.8% in basal secretions and 3.1% in the 50 to 60-min samples. CONCLUSIONS: Both pentagastrin and hypoglycaemia caused similar maximal secretion rates of pepsin 1, but hypoglycaemia caused greater secretion rates of total pepsin. The maximum concentrations and secretion rates of pepsin 1 occurred at different times from those of total pepsin and there is a threshold of total pepsin secretion below which pepsin 1 was not released.

Ecabet sodium prevents esophageal lesions induced by the reflux of gastric juice in rats.

We investigated the effect of ecabet sodium (ecabet) on rat acute esophageal lesions induced by reflux of gastric juice. Ligation of both pylorus and fore-stomach induced the reflux of gastric juice, decreased the amount of mucus and formed hemorrhagic lesions in the esophageal mucosa. Intragastric injection of ecabet reduced the pepsin activity and prevented both the decrease of mucus amount and formation of lesions. Ecabet enhanced the reduction in lesion formation induced by omeprazole and ranitidine without a change in decreased acid concentration and pepsin activity. Digestion of mucosa and the reduction in mucus were prevented by ecabet in the everted HCl and pepsin treated esophageal sac. These results indicate that ecabet prevents esophageal lesions by inhibiting pepsin activity as well as by protecting mucus from degradation. These further implicate the therapeutic potential of ecabet for prevention/treatment of GERD, especially in combination with a proton pump inhibitor or H(2)-antagonist.

Effect of dimethyl sulphoxide on the crystal structure of porcine pepsin.

The structure of porcine pepsin crystallized in the presence of dimethyl sulphoxide has been analysed by X-ray crystallography to obtain insights into the structural events that occur at the onset of chemical denaturation of proteins. The results show that one dimethyl sulphoxide molecule occupies a site on the surface of pepsin interacting with two of its residues. An increase in the average temperature factor of pepsin in the presence of dimethyl sulphoxide has been observed indicating protein destabilization induced by the denaturant. Significant increase in the temperature factor and weakening of the electron density have been observed for the catalytic water molecule located between the active aspartates. The conformation of pepsin remains unchanged in the crystal structure. However, the enzyme assay and circular dichroism studies indicate that dimethyl sulphoxide causes a slight change in the secondary structure and complete loss of activity of pepsin in solution.

Antioxidant activity and angiotensin I-converting enzyme inhibition by enzymatic hydrolysates from bee bread.

Enzymatic hydrolysates were prepared from bee bread using three proteases. The antioxidant properties of these hydrolysates were measured using four different methods. These had remarkable antioxidant activity similar or superior to that of 1 mM alpha-tocopherol. They also had high scavenging activities against active oxygen species as the superoxide anion radical and hydroxyl radicals. Moreover, they showed angiotensin I-converting enzyme inhibitory activities and the activities were similar to those from various fermented foods such as fish sauce, sake, vinegar, cheese, miso, and natto. The present studies reveal that enzymatic hydrolysates from bee bread are of benefit not only for the materials of health food diets, but also for in patients undergoing various diseases such as cancer, cardiovascular diseases, diabetes, and hypertension.

The effects of chronic consumption of heroin on basal and vagal electrical-stimulated gastric acid and pepsin secretion in rat.

OBJECTIVE: Addiction to opium and heroin is not only an important social and individual problem in the world but it also affects the human physiology and multiple systems. The aim of this study is to determine the effects of chronic heroin consumption on basal and vagus electrical-stimulated total gastric acid and pepsin secretion in rats. METHODS: The study was carried out in the Department of Physiology, Kerman University of Medical Sciences, Iran from August 2002 to June 2003. Both male and female rats weighing 200-250 g were used. Rats received daily doses of heroin intraperitoneally starting from 0.2 mg/kg to 0.1 mg/kg/day up to the maintenance level of 0.7 mg/kg and continued until day 12. After anesthesia, tracheotomy and laparotomy, gastric effluents were collected by washout technique with a 15 minutes interval. The total titrable acid was measured by manual titrator, and the total pepsin content was measured by Anson's method. Vagal electrical stimulation was used to stimulate the secretion of acid and pepsin. RESULTS: Heroin results in a significant decrease in total basal acid and pepsin secretions (4.10 +/- 0.18 mmol/15 minutes versus 2.40 +/- 0.16 mmol/15 minutes for acid, p<0.01, and 3.63 +/- 0.18 mg/15 minutes versus 3.11+/- 0.18 mg/15 minutes for pepsin, p<0.05). But, it does not produce any significant changes in acid and pepsin secretions in vagotomized condition. Heroin also causes a significant decrease in vagal-electrically stimulated acid and pepsin secretions (14.70 +/- 0.54 mmol/15 minutes versus 4.30 +/- 0.21 mmol/15 minutes for acid, p<0.01, and 3.92 +/-0.16 mg/15 minutes versus 3.37+/- 0.16 mg/15 minutes for pepsin, p<0.05). CONCLUSION: Heroin consumption decreases the total gastric basal and vagus stimulation of acid and pepsin secretion, but not in vagotomized condition. Heroin may decrease acid secretion by inhibiting vagal release of acetylcholine within the gastric wall. Other probable mechanisms include: presynaptic inhibition of acetylcholine release or depressing the vagal center, inhibition of pentagastrin induced acid secretion, inhibitory effects via central mechanisms, probably mediated by the opiate receptors. Further studies are needed to recognize the actual mechanism.

Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii.

Assay-guided fractionation of the ethanol extract of Tovomita krukovii resulted in the identification of four new xanthones (1 - 4) and ten known compounds (5 - 14). The structures of compounds 1 - 14 were determined by spectral data to be 3,5-dihydroxy-4-methoxyxanthone (1), 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (2), 1,3,5-trihydroxy-8-isoprenylxanthone (3), 1,5,7-trihydroxy-8-isoprenylxanthone (4), 1,3,7-trihydroxy-2-isoprenylxanthone (5), 1,5-dihydroxyxanthone (6), 1,6-dihydroxy-5-methoxyxanthone (7), 1,3,5-trihydroxyxanthone (8), 1,3,6-trihydroxy-5-methoxyxanthone (9), 1,6-dihydroxy-3,5-dimethoxyxanthone (10), 1,3,7-trihydroxyxanthone (11), 3-geranyl-2,4,6-trihydroxybenzophenone (12), betulinic acid (13), and 3,4-dihydroxybenzoic acid (14). Compounds 2, 3, 12 and 13 showed inhibitory effects against Candida albicans secreted aspartic proteases (SAP) with IC50 values of 15 microg/ml, 25 microg/ml, 40 microg/ml, and 6.5 microg/ml, respectively, while the other compounds were inactive. In addition, compound 12 showed activity against C. albicans, C. neoformans, S. aureus and methicillin resistant S. aureus (MRS).

Long-term lansoprazole control of gastric acid and pepsin secretion in ZE and non-ZE hypersecretors: a prospective 10-year study.

BACKGROUND: The majority of patients with Zollinger-Ellison syndrome require lifelong treatment with proton pump inhibitors. AIMS: To determine the efficacy of lansoprazole control of acid and pepsin secretion over the long term in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors. METHODS: Sixty-three hypersecretors (basal acid output > 15 mmol/h), 46 Zollinger-Ellison syndrome and 17 non-Zollinger-Ellison syndrome, with a total history of 15.4 and 19.2 years, respectively, were entered into a long-term prospective study using lansoprazole. Sixty-one were studied every 3 months for 1 year and then every 3-6 months up to 10 years during lansoprazole treatment with endoscopy, serum gastrin and gastric analysis, measuring both basal and stimulated pH and acid and pepsin secretion. Doses were individually optimized and adjusted to keep the basal acid output at < 5 mmol/h in intact patients and < 1 mmol/h in antrectomized Zollinger-Ellison syndrome patients. RESULTS: The dose of lansoprazole could not be predicted a priori from pre-treatment acid or pepsin output, serum gastrin, prior omeprazole dose or diagnosis or prior complications. The median dose was approximately 80 mg/day, with a wide range from 15 mg every other day to 360 mg/day, and generally stabilized by 12 months. However, as doses were adjusted over time for indications, almost half the patients required higher doses. With adjustments, the basal acid output was maintained in the target range in > 90% of intact patients and in 80% of antrectomized patients. Gastric juice pH increased from approximately 1.2 before therapy to > 3.4 during therapy. Serum gastrin in Zollinger-Ellison syndrome patients, after excluding five outliers, did not change over the course of therapy, but doubled in non-Zollinger-Ellison syndrome patients. There were no adverse events due to lansoprazole, and routine laboratory studies remained normal. CONCLUSIONS: The dose of lansoprazole for hypersecretors cannot be predicted, and thus needs to be optimized empirically on an individual basis. With continued periodic adjustments, almost half the patients required increased doses, while safe dose reduction was possible in only one-quarter. When individually optimized, lansoprazole proved to be safe and effective in the control of secretion for the treatment of both Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors for up to 10 years.

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models.

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 +/- 0.9), when given in the dose of 10-50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.

Peptides derived from HIV-1 Vif: a non-substrate based novel type of HIV-1 protease inhibitors.

The retroviral protease (PR) is absolutely essential for completion of human immunodeficiency virus multiplication cycle, and cannot be replaced by any cellular function. Thus PR, like reverse transcriptase, is an ideal target for the development of anti-AIDS therapy. A large number of human immunodeficiency virus type-1 (HIV-1) PR inhibitors have been developed, and several are currently used as anti-AIDS drugs. These inhibitors are mainly based on the natural PR cleavage sites within the viral Gag and Gag-Pol precursors. The major difficulty encountered while using anti-HIV therapeutic agents in patients has been the rapid emergence of drug-resistant viral strains. Most of the mutations which convert the PR into inhibitor-resistant are located within the substrate binding subsites of the enzyme. Recently, it has been shown that the HIV-1 auxiliary protein Vif, and especially the N-terminal half of Vif (N'-Vif) specifically interacts with the viral PR and inhibits its activity. We now show that efficient inhibition of HIV-1 PR activity can be achieved using Vif-derived peptides. Based on the above model we have performed peptide mapping of N'-Vif in order to find a small peptidic lead compound which inhibits PR activity. The screening revealed that peptides derived from two regions in Vif spanning from residues 30-65 and 78-98 inhibit PR activity in vitro, specifically bind HIV-PR and inhibit HIV-1 production in vivo. Further mapping of these regions revealed the lead compounds Vif81-88 and Vif88-98. These peptides specifically inhibit and bind HIV-1 PR, but do not affect pepsin and rous sarcoma virus protease. In contrast to other known PR inhibitors, these peptides are not substrate-based and their sequences do not resemble the sequences of the natural PR substrates (cleavage sites). Moreover, the Vif-derived peptides themselves are not cleaved by HIV-1 PR. Conversion of the lead peptides into small backbone cyclic peptidomimetics is taking place nowadays in order to turn these lead compounds into metabolically stable selective novel type of HIV-PR non-substrate-based inhibitors.

Effect of Tityus serrulatus scorpion toxin on serum gastrin levels in anaesthetized rat.

Scorpion toxin induces gastric secretion of acid and pepsin in rats. These effects seem to be mediated by the release of acetylcholine and histamine. However, the role of gastrin in the scorpion-toxin-induced gastric secretion is unknown. We describe the effects of the T1 fraction purified from Tityus serrulatus scorpion venom on serum and on antral tissue gastrin levels in anaesthetized rats. Gastrin levels in serum and in the antral mucosa were measured before and at intervals 5, 15, 30, 60, 90 up to 120 min after the intravenous injection of saline or the T1 fraction of scorpion venom (0.25 mg/kg) into anaesthetized rats. Antral G-cells were submitted to immunocytochemistry and electron microscopy. The data on gastrin were correlated with the gastric juice volume, and the acid and pepsin output increases induced by toxin. Scorpion toxin induced a significant increase in volume, acid output and pepsin output of gastric juice and gastrin serum levels 15-60 min after injection. Simultaneous measurements of antral gastrin levels did not show significant effects. The number of dense, intermediate and empty granules per microm(2) in the cytoplasm of antral G-cells was not significantly changed 60 min after saline or toxin injection. Scorpion toxin significantly increased serum gastrin; levels in rats.

[Impact of specific antituberculosis therapy on gastrointestinal tract in children]. / Vliianie spetsificheskoi protivotuberkuleznoi terapii na zheludochno-kishechnyi trakt u detei.

Forty eight children aged 3 to 14 years treated at hospital for various tuberculous abnormalities were examined. The findings suggest that the use of antituberculosis agents in children with normal acid and pepsin production failed to have a noticeable effect on the gastrointestinal tract. Moreover, the 6-month use of highly and moderately effective antituberculosis agents produced no effect on the aggressive properties of gastric juice. It is necessary to prescribe enveloping and mucus-forming agents to reduce the potential side effect of tuberculostatic therapy.

Effects of ranitidine or nocloprost on the selected gastric juice components in the patients with the gastric ulcer.

The 24 patients with gastric ulcer were treated ranitidine (2 x 150 mg daily) or nocloprost (2 x 200 micrograms daily). The effects of these drugs on the gastric juice components were measured. We evaluated hydrochloric acid, total protein, pepsin and some carbohydrates components secretion. We showed, that ranitidine decreased significantly total protein, fucose, N-acetylneuraminic acid and hexoses contents in the gastric juice in the basal secretion; the same tendency was observed in the pentagastrin-stimulated secretion. The similar direction of the changes, but weakly expressed was confirmed in the patients treated with nocloprost. It has been shown, that ranitidine modified the gastric mucin components content, what can suggest diminished degradation of mucus directly adhering to the gastric mucosa.

Effect of peptide YY on gastric motor and secretory activity in vagally innervated and denervated corpus pouch dogs.

In this study, we examined the mechanism by which constant intravenous infusion of physiological doses of PYY affects gastric secretion and motility in the vagally innervated (Pavlov) and denervated (Heidenhain) corpus pouch. As a result, only in the Heidenhain pouch, PYY at a dose of 100 pmol/kg-h significantly inhibited gastric secretion in the interdigestive and postprandial states. A dose of 300 pmol/kg-h inhibited the gastric secretion in both types of pouch, but inhibition in the Pavlov pouch was less than in the Heidenhain pouch. The inhibitory effect of PYY on phase III contractile activity was dose-dependent and significant, except in the Heidenhain pouch, and no dose of PYY had any effect on postprandial gastric motility. After all, vagal denervation enhanced the inhibitory effect of PYY on gastric secretion, but abolished the inhibitory effect on phase III contractile activity. Our findings strongly suggest that the inhibitory effect of PYY on gastric secretion is in part mediated by a non-vagal pathway and the inhibitory effect of PYY on gastric motor activities is completely dependent on vagal innervation, but the vagus nerve acts as an inhibitory modulator of the inhibitory effect of PYY on gastric secretion.

[The secretory function of the gastric glands under the joint action of acetylcholine, adenosine triphosphoric acid and histamine]. / Sekretorna funktsiia shlunkovykh zaloz pry spil'nii diï atsetylkholinu, adenozyntryfosfornoï kysloty ta histaminu.

The combined action of acetylcholine (in a dose of 0.5 mg/kg), ATP (0.5 mg/kg) and histamine (0.05 mg/kg) on the secretory function of the gastric glands has been studied. Combined action of acetylcholine and histamine has induced an increase in the secretion volume rate, acid producing and pepsin discharge functions of the gastric glands. The ATP effect of the background of histamine-stimulated secretion increased acid production and pepsin discharge but less than acetylcholine and histamine did. Simultaneous action of acetylcholine, ATP and histamine has led to potentiation of acetylcholine and ATP effects of the volumetric secretory rate and to their summarized action on pepsin discharge. The conclusion is made that activation of the secretory processes with simultaneous action of the above-mentioned mediatory substances is associated with the participation of corresponding intracellular secondary messengers and start of some cascade reactions.

Different pharmacological actions of adenosine on gastric function and mucosal damage in normotensive and spontaneously hypertensive rats.

It has been reported that there are functional defects in the purinergic system in spontaneously hypertensive rats (SHR). The following experiments examined the gastric effects of adenosine in these animals. SHR had a significantly higher gastric mucosal blood flow (GMBF), but the secretion of acid and pepsin was not different from that of normotensive counterparts. In SHR, adenosine (s.c. 3.75 or 7.5 mg/kg) time- and dose-dependently decreased gastric acid secretion and GMBF. The nucleoside, however, did not affect the pepsin secretion. In normotensive rats, gastric acid secretion was also reduced, but not to the extent of SHR. The GMBF was increased instead. Adenosine potentiated ethanol-induced mucosal damage in SHR, which was likely caused by GMBF reduction. It is concluded that adenosine produces a greater depressive action on the stomach in SHR. These differential actions are probably due to the genetic difference between the two types of animals.

Role of tumor necrosis factor alpha release and leukocyte margination in indomethacin-induced gastric injury in rats.

BACKGROUND/AIMS: Several studies have shown that polymorphonuclear neutrophil leukocyte (PMN) margination is an early and critical event in the pathogenesis of gastric mucosal injury caused by nonsteroidal anti-inflammatory drugs. Tumor necrosis factor (TNF) alpha is a proinflammatory cytokine that causes PMN margination by up-regulating expression of adhesion molecules on both PMN and endothelial cells. This study investigated whether substances that modulate TNF synthesis and release influence PMN margination and indomethacin-induced gastric damage. METHODS: Rats were treated with several doses of indomethacin alone or in association with substances known to increase (interleukin 2 and lipopolysaccharide) or inhibit (pentoxifylline, dexamethasone, granulocyte colony-stimulating factor [G-CSF]) TNF synthesis and release. RESULTS: Indomethacin administration caused dose-dependent damage and increased PMN margination and plasma TNF concentrations. Pretreatment with interleukin 2 and lipopolysaccharide significantly increased TNF release, PMN margination, and gastric mucosal damage, but administration of dexamethasone, pentoxifylline, and G-CSF provided almost total protection. The administration of G-CSF alone caused a significant increase in gastric PMN margination but protected against the indomethacin-induced gastropathy. CONCLUSIONS: Agents that regulate TNF synthesis and release influence gastric susceptibility to indomethacin by modulating PMN margination. G-CSF increased PMN infiltration but protected against the mucosal injury, suggesting that PMN margination alone is not sufficient to induce mucosal damage.

Interaction of polyacrylates with porcine pepsin and the gastric mucus barrier: a mechanism for mucosal protection.

1. The mechanism of interaction of the polyacrylates, carbopols with the mucus barrier in vivo has been investigated in vitro. 2. Carbopol caused a dramatic increase in the viscosity of porcine gastric mucin solutions that was up to 19-fold greater than that of the sum of the individual polymers. 3. The mucin-carbopol interaction was stable after an initial 30 min period for up to 36 h at 25 degrees C or 37 degrees C. It was reduced by increasing the temperature from 20 degrees C to 45 degrees C, was unaffected by pH and ionic strength, but was enhanced by Ca2+. 4. The magnitude of the interaction between mucin and carbopol depended on the polymeric structure of the mucin and the molecular size and level of cross-linking of the carbopol. 5. The interactions were reversible and increased with increasing carbopol and mucin concentration. The dramatic increase in viscosity can be explained in terms of space filling by the mucin molecules leading to predominantly carbopol-carbopol interactions. 6. Carbopol 934P inhibits pepsin hydrolysis and therefore has potential as a mucosal protective agent in vivo.

Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer.

Helicobacter pylori (H pylori) raises serum gastrin but it is unclear whether this stimulates increased acid secretion. Gastrin mediated acid secretion and plasma gastrin after the intravenous infusion of gastrin releasing peptide was studied in nine H pylori negative and nine H pylori positive healthy volunteers, and in 11 duodenal ulcer patients. Nine of the last group were re-examined one month after eradication of H pylori. The median acid output (mmol/h) to gastrin releasing peptide (40 pmol/kg/h) in the H pylori positive healthy volunteers was 15.1 (range 3.3-38.3), which was three times that of the H pylori negative healthy volunteers (median = 5.5, range 1.0-9.0) (p < 0.02). The median acid output in the duodenal ulcer patients with H pylori was 37 (range 8.5-57), which was > six times that of the H pylori negative healthy volunteers. Eradication of H pylori in the duodenal ulcer patients lowered their acid secretion by a median of 66% (range 30%-80%) (p < 0.01) and to values equivalent to the H pylori positive healthy volunteers. The pepsin output in response to gastrin releasing peptide followed the same pattern as the acid output. The median plasma gastrin concentrations during gastrin releasing peptide were similar in the H pylori positive duodenal ulcer patients (150 ng/l, range 95-400) and H pylori positive healthy volunteers (129 ng/l, range 23-420) and both were appreciably higher than H pylori negative healthy volunteers (60 ng/l, range 28-135) (p < 0.005 for each). Eradication of H pylori lowered the plasma gastrin in the duodenal ulcer patients to values equivalent to the H pylori negative healthy volunteers. These findings show a threefold increase in acid secretion in H pylori positive healthy volunteers that is explained by H pylori induced hypergastrinaemia and a sixfold increase in acid secretion in the duodenal ulcer patients that is explained by the combination of H pylori induced hypergastrinaemia and an exaggerated acid response to stimulation by gastrin. Eradicating H pylori lowers gastrin mediated acid secretion by 66% in duodenal ulcer patients as a result of the resolution of the hypergastrinaemia. Increased gastrin mediated acid secretion seems to be the key factor in the pathophysiology of duodenal ulceration and explains the role of H pylori infection in the disorder.