Collection Of Gastric Juice Research Articles

Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement.

Background: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. Methods: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1β, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-β) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. Results: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-β, GM-CSF, IL-17 and ET-1 (p < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1β, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.

Gastric juicepHmeasurement in horses: Three‐quarters of a century of history!

SummaryInhibition of gastric acid and increased stomachpH&gt;4.0 is currently accepted as the mainstay of treatment for gastric ulcers in horses. Measurement of gastricpHis complicated and requires placement of a cannula and collection of gastric juice or placement ofpHelectrodes in the stomach. Since the distance from the nares to the stomach is approximately 200 cm, finding a system with apHelectrode with this length is difficult, not to mention difficult to maintain. There has been a fascination with the measurement of gastric juicepHin horses that has covered three‐quarters of a century starting with a fistula model in 1933 and culminating in a recent technique described in this issue. Placement of gastric cannulas and variouspHelectrodes have been used to measure gastric juicepHin horses in the past and present, but the future may require more sophisticated methods as we look at the efficacy of different formulations of acid suppressive drugs for treatment of equine gastric ulcer syndrome.

Особливості періодичної активності шлунка за умов дисбалансу NO-ергічної системи

Nitric oxide is the main inhibitory mediator of the gastrointestinal smooth muscles’ relaxation which stimulates duodenal mucus and bicarbonate secretion. More recent studies have demonstrated that NO also protected the gastrointestinal tract by inhibiting gastric acid secretion. In this study we investigated gastric secretory and motor activity considering the NO imbalance condition. The experiments were carried out on male white laboratory rats (200–230 g). The control group was treated with 0.9% NaCl solution. The injections of NO donator (1.5 mg/kg of 0.1% (Sigma-Aldrich) sodium nitroprusside solution) were made in the second and the third groups during 6 and 12 days. The fourth and the fifth group were treated with NO synthesis inhibitor (40 mg/kg of 1% solution (Sigma-Aldrich) Nω-nitro-L-arginine) during 6 and 12 days respectively. Recording of gastric myoelectric activity (GMA) and gastric juice collection were carried out under anesthesia (ketamine, 110 mg/kg). Next, its volume, pH, glycoprotein and pepsin were measured. Within 6-days stimulation of NO excess decreased gastric juice volume by 47% and increased pH compared to control samples. Pepsin level increased by 62% and glycoprotein level decreased by 68% compared to the checkpoint. After 6 days of L-NNA injections we observed the increase of gastric juice secretion volume (78%) and pH level, however, pepsin concentration remained unchanged. Glycoprotein level increased by 21% compared to control samples. After 12 day NO synthesis inhibitor injections gastric secretion volume increased by 85%. Gastric juice pH level was 200% higher than the control value and exceeded gastric juice pH level (62%) in the third group. In addition, pepsin level tended to decrease when NO deficiency simulation was prolonged. Glycoprotein level decreased by 41% compared to control samples and by 51% compared to the third group. Pepsin level decreased after 12 day NO-inhibitor injections as gastric juice pH level increased. After 12 day Na-nitroprusside treatment, gastric myoelectric index decreased by 42% compared to the checkpoint. The type of contractions is typical to the I phase of the basic electrical rhythm (BER). Also, retrograde entrainment of duodenal rhythm took place. After 6 day L-NNA injections, GMA was the same as the period between II and III phase of BER. Late second and early third phases predominated, while the I phase wasn’t detected during the recording. In case of long-lasting disorder of NO-system, motor index value significantly differed from the control group samples and depended on the duration of NO-synthase blocking. On the 6th day of L-NNA treatment, the level of motor index increased 1.5 times. GMA phases could be identified only on the basis of motor index values. Stomach’s own rhythms disappeared and duodenogastric reflux resulted in domination of duodenal rhythms. After 12 day L-NNA injections, duration of the II and III phases increased while the I phase of gastric BER disappeared; gastric motor index decreased by 27%. After considering the results of the current investigation, it can be stated that NO system imbalance leads to desynchronization of gastric active phases and, perhaps, reassigns the influence of different compensatory-adaptive mechanisms. The longer is the L-NNA treatment, the more gastric functions are imbalanced and the stronger is the process of destruction.

Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: Role of nitric oxide and prostaglandins

This study investigated the possible mechanisms underlying the gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats. Rats were randomly assigned to vehicle-, simvastatin-, simvastatin + l-arginine- and simvastatin + N(G)-nitro- l-arginine methyl ester (L-NAME)-pretreated groups for two weeks. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Gastric juice parameters (total acid output, pepsin activity and mucin concentration) were determined. The stomachs tissues were used for determination of gastric mucosal lipid peroxides, superoxide dismutase, catalase, total nitrites and prostaglandin E 2 levels. Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration. Simvastatin significantly increased the gastric mucosal total nitrite and prostaglandin E 2 levels. Additionally, simvastatin attenuated the elevations in gastric mucosal superoxide dismutase observed with indomethacin. The gastroprotective effect afforded by simvastatin was significantly augmented by coadministration with l-arginine (a nitric oxide precursor) and inhibited by coadministration with L-NAME (a nitric oxide synthase inhibitor). Results confirm a gastroprotective effect for simvastatin, and indicate that the anti-ulcer effect of simvastatin is mediated by scavenging free radicals, increasing nitric oxide and prostaglandin E 2 levels, and increasing gastric juice mucin production. We conclude that simvastatin represents a more suitable antihyperlipidemic therapy for patients who are at risk of gastric ulcers that were induced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Gastric secretion elicited by conditioning in rats

Objective. To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. Material and methods. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. Results. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. Conclusions. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

Role of Rosiglitazone as a Gastroprotective Agent Against Indomethacin-Induced Gastric Mucosal Injury in Rats.

BackgroundRosiglitazone, an insulin sensitizing agent, has been recently implicated in the control of inflammatory processes and modulation of expression of various cytokines such as tumor necrosis factor (TNF-α). However, its mechanistic effect of gastric mucosal integrity remains to be elucidated.MethodsThe present study was designed to determine effect of rosiglitazone on gastric mucosal lesions induced by indomethacin (IND) in rats. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of IND (30 mg/kg).ResultsIND administration caused a significant decrease in the volume of gastric juice mucin and gastric mucosal nitrite and prostaglandin E2 (PGE2) levels. This was accompanied by a significant increase in gastric juice free and total acidity and pepsin activity. In addition, an elevation in the gastric mucosal lipid peroxide and serum TNF-α level was observed. Pretreatment with rosiglitazone (10 mg/kg, orally, for 1 weeks) resulted in a significant reduction in the elevated gastric mucosal lesions and lipid peroxides levels. This was associated with a marked increase in gastric juice mucin and a reduction in TNF-α level. Moreover, rosiglitazone significantly increased the gastric mucosal total nitrite and PGE2 levels.ConclusionsRosiglitazone exerts a gastroprotective effect against IND-induced gastric mucosal lesions and its anti-ulcer effect is mediated via scavenging free radicals, increasing NO, PGE2 and mucus production in addition to its anti-inflammatory mechanisms. Thus, rosiglitazone could be a relevant drug for patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and at high risk of developing gastric ulceration.

Mechanisms of gastroprotective effect of eugenol in indomethacin‐induced ulcer in rats

Possible mechanisms underlying the gastroprotective effect of eugenol against indomethacin-induced ulcer in rats were investigated. Pyloric ligation was performed for collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal (i.p.) injection of indomethacin (30 mg/kg). Pretreatment with a single dose of eugenol (100 mg/kg, orally), 1 h before indomethacin administration caused significant reductions in gastric mucosal lesions, gastric acid outputs and pepsin activity associated with a significant increase in mucin concentration. Additionally, eugenol significantly attenuated the elevations in gastric mucosal malondialdehyde and total nitrite, and the decrease in reduced glutathione observed with indomethacin. The protective effect afforded by eugenol was significantly inhibited by prior administration of glibenclamide, the ATP-sensitive potassium (K(ATP)) channel blocker, but not by prior use of ruthenium red, the transient receptor potential vanilloid 1 (TRPV1) antagonist. The results indicate that the anti-ulcer effect of eugenol is mediated by opening of K(ATP) channels, scavenging free radicals, decreasing acid-pepsin secretion, increasing mucin production, and preventing the deleterious rise in nitric oxide level.

Endogastric capsule for E-cadherin gene (CDH1) promoter hypermethylation assessment in DNA from gastric juice of diffuse gastric cancer patients

BackgroundWe investigated whether an endogastric capsule (EC) may be a valuable tool for collecting DNA from exfoliated cells from the gastric mucosa and for carrying out an analysis of promoter methylation status of the E-cadherin (CDH1) gene in poorly differentiated, diffuse gastric cancer (DGC). Material and methodsConsecutive patients with a confirmed diagnosis of poorly differentiated DGC underwent collection of gastric juice by EC. Subjects without cancer and premalignant lesions were also accrued as controls. The samples of gastric juice were processed for DNA isolation and amplification. Then they were used for analysis of CDH1 promoter hypermethylation. ResultsThe procedure successfully allowed the analysis of CDH1 promoter hypermethylation in 20 patients and 14 controls. This pilot study showed feasibility of the procedure and a significantly different CDH1 promoter hypermethylation status between DGC patients and controls was detected. ConclusionsThe EC may represent an innovative and noninvasive tool for the analysis of a specific epigenetic change in DGC patients. Our findings deserve additional studies as this method may represent a cost-effective tool for early detection of sporadic as well as hereditary DGC in CDH1 germline mutations carriers.

Induced Secretion Of Pepsin-Rich Gastric Juice In The Rat By The Crude Extract From &lt;i&gt;Elaeophorbia drupifera&lt;/i&gt; Leaves: A Dual Pathway Mechanism

Ninety male white Wistar rats (200 - 320g) were fasted for 48 hours, and used in the experiments for the collection of gastric juice according to the method of Shay et al, 1954. The extract (2.5 - 200 mg/kg) increased the secretion of gastric juice which was low in volume but rich in pepsin concentration. The adrenergic drugs dihydroergoergotoxine (hydergine) (1.25 mg/kg) and phentolamine (1.5 mg/kg) both also increased gastric secretion, which were high in volume, titratable acidity and total acid output but low in pepsin concentration. When the extract (20 mg/kg) was given in combination with either of the two sympatholytic drugs, the pepsin concentration in the juice was richer than that evoked by either of the two drugs alone. Also, atropine-extract combination significantly (P E. drupifera leaf extract-induced secretion of gastric juice. One of which may be mediated by the muscarinic cholinoceptors and the other via histamine H 2 -receptor subtype. Key words: Elaeophorbia drupifera; gastric juice, muscarinic- and histaminergic-receptors Nigerian Journal of Physiological Sciences Vol.19(1&2) 2004: 53-59

AZD0865, A POTASSIUM-COMPETITIVE ACID BLOCKER (P-CAB), HAS A LONG DURATION OF EFFECT IN THE RAT

Purpose: AZD0865 is a potassium-competitive acid blocker (P-CAB) in development forthe treatment of acid-related diseases. This study investigated the duration of effect of AZD0865 in the rat. Methods: Stimulated (pentagastrin + carbachol) acid secretion was measured in 4 groups of 8 chronic fistula rats after single oral doses of AZD0865 at 0, 1, 10 and 50 /μmol//kg (>6 days washout between doses), with various intervals between dosing and a 2-h period of stimulation and collection of gastric juice. In addition, responses were also recorded 24 h after a 5-day period of repeated dosing at 1 and 10 /μmol/kg/day. In follow-up experiments, secretory responses were assessed 24 h after a single dose and 5 days repeated administration of AZD0865 at 0,1 and 5 /μmol//kg/day, and AZD0865 concentration was determined using reversed-phase liquid chromatography and fluorescence detection both in plasma collected after the secretory tests and in titrated samples of gastric juice (limit of quantification [LOQ] 20 and 2 nmol/L, respectively). Results: Inhibition of acid output 24 h following single doses of AZD0865 (1, 10 and 50 /μmol/kg) was 47%, 95% and 100%, respectively. Acid secretion returned to control levels by 36, 48 and 96 h, respectively, post-dose. The inhibition 24 h following 5 days' repeated doses of AZD0865 (1, 10 /μmol//kg/day) was 49% and 93%, respectively. In follow-up studies, inhibition 24 h after single and repeated doses was 37% and 21% at 1 /μmol/kg and 78% and 82% at 5 /μmol/kg. Single and repeated doses resulted in similar AZD0865 concentrations in plasma 25 h post-dose: <20 nmol/L (i.e. <LOQ in 7 of 8 rats) at 1 /μmol/kg; and (mean ± SEM) 59 ± 7 and 71 ± 4 nmol/L, respectively, at 5 /μmol/kg. The concentration of AZD0865 in gastric juice 23–25 h after single and repeated doses was: 29 ± 8 and 35 ± 8 nmol/L at 1 /μmol/kg; and 199 ± 36 and 184 ± 22 nmol/L at 5 /μmol/kg, respectively. Conclusions: AZD0865 provides dose-dependent inhibition of acid secretion over the 24-h period. There is no accumulation of 24-h antisecretory effect and no increase in the concentration of AZD0865 in plasma or gastric juice during repeated administration. The level of AZD0865 in gastric juice is higher than in plasma reflecting concentration of AZD0865 in the acidic canaliculus of the parietal cell. Consequently, the duration of effect of AZD0865 in the rat outlasts the time when AZD0865 is detectable in plasma.

Gastric analysis using 15-minute gastric juice collection during esophagogastroduodenoscopy (EGD)

Gastric analysis using 15-minute gastric juice collection during esophagogastroduodenoscopy (EGD)

Gastric-juice ammonia assay for diagnosis of Helicobacter pylori infection and the relationship of ammonia concentration to gastritis severity.

To determine the test characteristics of gastric-juice ammonia concentration as measured by an ion-selective electrode and a rapid ammonia detection device for the diagnosis of Helicobacter pylori infection and to assess the relationship between gastric-juice ammonia concentration and the severity of gastritis. Patients undergoing upper endoscopy had collection of gastric juice that was tested for ammonia using an ion-selective electrode and a rapid ammonia assay device that uses a pH-indicating membrane. A receiver operating characteristic curve was calculated for ammonia concentration. Severity of gastritis was graded using the Sydney classification (1) and correlated to gastric-juice ammonia concentration. Patients also underwent H. pylori testing by IgG serology, rapid urease testing, and histological special stain. Ammonia testing results were compared with a reference standard of two of three positive tests and with a second reference standard of a positive serology. 73 patients underwent endoscopy and collection of gastric juice. The receiver operating characteristic curve indicated an optimal cutoff value of 5 mM, yielding a sensitivity of 67%, specificity of 93%, positive predictive value of 67%, and negative predictive value of 93% (compared with the combined reference standard). The rapid NH3-testing device yielded a sensitivity of 83%, specificity 63%, positive predictive value 31%, and negative predictive value 95%. The severity of neutrophilic (p = 0.001) and mononuclear cell (p = 0.003) infiltration were significantly correlated with gastric-juice ammonia concentration. Measurement of gastric-juice ammonia concentration by ion-selective electrode or rapid detection device is a relatively insensitive and nonspecific means of H. pylori diagnosis. Gastritis severity increases with gastric-juice ammonia concentration.

Gastric-juice ammonia assay for diagnosis of Helicobacter pylori infection and the relationship of ammonia concentration to gastritis severity

OBJECTIVES: To determine the test characteristics of gastric-juice ammonia concentration as measured by an ion-selective electrode and a rapid ammonia detection device for the diagnosis of Helicobacter pylori infection and to assess the relationship between gastric-juice ammonia concentration and the severity of gastritis. METHODS: Patients undergoing upper endoscopy had collection of gastric juice that was tested for ammonia using an ion-selective electrode and a rapid ammonia assay device that uses a pH-indicating membrane. A receiver operating characteristic curve was calculated for ammonia concentration. Severity of gastritis was graded using the Sydney classification (1) and correlated to gastric-juice ammonia concentration. Patients also underwent H. pylori testing by IgG serology, rapid urease testing, and histological special stain. Ammonia testing results were compared with a reference standard of two of three positive tests and with a second reference standard of a positive serology. RESULTS: 73 patients underwent endoscopy and collection of gastric juice. The receiver operating characteristic curve indicated an optimal cutoff value of 5 mM, yielding a sensitivity of 67%, specificity of 93%, positive predictive value of 67%, and negative predictive value of 93% (compared with the combined reference standard). The rapid NH 3-testing device yielded a sensitivity of 83%, specificity 63%, positive predictive value 31%, and negative predictive value 95%. The severity of neutrophilic ( p = 0.001) and mononuclear cell ( p = 0.003) infiltration were significantly correlated with gastric-juice ammonia concentration. CONCLUSIONS: Measurement of gastric-juice ammonia concentration by ion-selective electrode or rapid detection device is a relatively insensitive and nonspecific means of H. pylori diagnosis. Gastritis severity increases with gastric-juice ammonia concentration.

Neutrophil chemotaxis in gastric mucosa

This prospective study compares levels of neutrophil chemotactic activity (NCA) in gastric juice to the neutrophil count in gastric biopsies. Sixty-three male patients enrolled in the study and had antral biopsies following collection of gastric juice during esophagogastroduodenoscopy. Biopsies were examined for the magnitude of gastritis, tissue PMN count, and presence of Helicobacter pylori. Secretions were assayed for neutrophil chemotactic activity. Results show an increase in NCA and in tissue PMN counts with increasing severity of gastritis. H. pylori-positive patients had higher levels of NCA and PMN than H. pylori-negative patients. Wide variability in NCA levels preclude a direct correlation between NCA and PMN counts.

Studies in gastric carcinogenesis. V. The effects of ascorbic acid on N-nitroso compound formation in human gastric juice in vivo and in vitro

The concentrations of nitrite, thermo- and acetic acid-labile TEA-responsive compounds (TACs) and N-nitroso compounds (NOCs) as a group were measured in human gastric juice collected just before and 1, 2 and 4 h after oral ingestion of 1 g ascorbic acid (AA) or 200 mg sodium nitrate, separately or in combination. Individual responses of gastric [nitrite] following ingestion of AA alone varied widely, with both decreases and increases being observed, and showed no correlation with gastric pH. While a mixed response was also noted for [NOC] and [TAC], substantial decreases were observed in 5/6 individuals with initial [NOC] greater than 0.2 microM and 3/3 individuals with initial [TAC] greater than 0.2 microM, implying that (i) AA effectively inhibited gastric nitrosation and (ii) a basal amount of NOCs and TACs was present in gastric juice which could not be lowered by AA ingestion. Statistical analysis indicated that global mean values of gastric [NOC] were significantly reduced (P less than 0.02) 1-4 h after ingestion of AA. Ingestion of 200 mg sodium nitrate alone resulted in increases in gastric [NOC], which in some cases were very substantial. While nitrosation appeared lower following ingestion of the same dose of nitrate in combination with 1 g AA, the difference from the effects of nitrate alone was not statistically significant. In aqueous buffer, pH 2.5, and in the presence of 1 mM AA, 50 microM nitrite was consumed with a t1/2 of 50 min only if molecular oxygen had first been removed from the system. In the presence of oxygen, no consumption of nitrite could be detected in 50 min, reflecting nitrite recycling (oxidation of nitric oxide to higher oxides of nitrogen and hydrolysis back to nitrite). It is likely that nitrite recycling occurring after collection of gastric juice accounted for the inconsistent responses of gastric nitrite following ingestion of AA. Incubation of human gastric juice, pH 2.5, in vitro in the presence of 50 microM sodium nitrite for 60 min resulted in an increase of [NOC] and [TAC] from 0.10 to 0.70 and 1.10 microM respectively. Nitrosation was efficiently inhibited by AA, 2.27 mM AA resulting in 87 and 100% inhibition respectively. Removal of oxygen from the reaction mixture did not have any significant effect on the extent of nitrosation in the presence or absence of AA.

Sequential evaluation of gastric intraluminal prostaglandin E2 release, acid secretion and DNA-flow cytometry in N-methyl- N-nitro- N-nitrosoguanidine gastric carcinogenesis in the rat

The study was initiated to evaluate the sequential changes of gastric intraluminal prostaglandin E2 (PGE2), gastric acid secretion and of the DNA-flowcytometric patterns during gastric carcinogenesis induced by 45-week N-methyl-N-nitro-N-nitrosoguanidine (NG) administration in the rat. Twenty male chronic gastric fistula Sprague—Dawley rats received NG solution (120 mg/l) for 45 weeks and 20 were used as controls. Samples of gastric juice (1 h) were obtained from all animals under basal conditions and every 5 weeks until the end of the experiment. Aliquots of gastric juice were titrated with 0.1 N NaOH. Other aliquots were extracted with ethylacetate and processed for specific PGE2 RIA. On the day following gastric juice collection a gastric lavage and gastric biopsies (n=4) were obtained through the fistula and processed for flowcytometry. All surviving animals were killed after 45 weeks and histology was obtained. The incidence of cancer in NG treated chronic gastric fistula rats was 66%. Flowcytometry segregated at an early stage (30–35 weeks) those animals which were to develop gastric carcinoma from those which were not. Administration of NG decreased gastric secretion volume, acid and intraluminal PGE2 concentration both in animals developing and not developing cancer. During the last 10 weeks a sharp rise in gastric intraluminal PGE2 concentration was observed in tumor-bearing animals only probably due to production by tumor cells. Prostaglandin deficiency may contribute to the NG-induced mucosal damage and may be involved in gastric carcinogenesis.

A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig

A new model for measuring gastric secretory parameters in awake guinea pigs is described. A chronic cannula was surgically implanted in the stomach of each guinea pig. The rates of gastric secretion and changes in intragastric volume were measured using a dye dilution technique. In contrast to previous techniques in small laboratory animals, there was no collection of gastric juice via drainage, no oral intubation for aspiration was involved, no special or sophisticated equipment was used, no anesthesia was employed, and there was no stress associated with acute surgery. This method offers a valuable advantage by combining the chronic gastric cannula with a dye dilution technique in that the same animal can be used several times and finally, several gastric secretory parameters can be measured simultaneously. The animals were used from 3 weeks to 10 months after surgery and as many as 15 studies were performed on the same guinea pig. Samples were collected at 10-min intervals and analyzed for acid and dye concentration from which the onset and kinetics of gastric secretion were followed. Basal gastric secretion (11.8 ± 1.6 μeq/kg/min; all mean ± 1 SEM) was increased within 20 min after subcutaneous infusion of histamine (30 μg/kg/hr) and peaked by 40–60 min at a mean acid output rate of 41 ± 3 μeq/kg/min. Histamine also increased the intragastric volume from 6.3 to 13.4 ml as it increased fluid output from 1.6 ± 0.1 ml/10 min to 3.4 ± 0.2 ml/10 min. The increase in acid output caused by histamine was inhibited by the H 2-antagonists cimetidine (3 μmole/kg) and ranitidine at 0.5 μmole/kg. Omeprazole (1.2 μmole/kg), an HK-ATPase inhibitor, almost abolished acid output under both basal and histamine-stimulated conditions. Thus, the present method is simple and suitable to study the physiology and pharmacology of gastric secretion in the guinea pig with a particular emphasis on the action of histamine. Furthermore, because of the species involved, there is also a significant economical advantage and the guinea pig can also be used as a potential model for studying experimental ulcer.

Inhibition of gastric acid secretion by blood drawing from an indwelling venous needle.

To investigate a possible inhibitory effect of blood drawing through an indwelling forearm vein needle on gastric acid secretion, 11 subjects were studied on four occasions each. The first session was for adapting the subject to the 3-hr collection of gastric juice. In 7 subjects the second through fourth sessions gave three conditions in balanced order: (1) an indwelling forearm vein needle and the withdrawal of 5 or 10 cc of blood every 20 min, (2) only a nonfunctional "dummy" needle implanted subcutaneously in the forearm skin, and (3) the control condition with no needle. In four additional subjects the sessions were identical except that condition (1) involved an indwelling forearm vein needle kept open by a slow infusion of saline solution and no blood was drawn. Phenol red recovery from an initial intragastric injection was measured in all. Results showed that blood drawing, but not saline infusion or venipuncture per se, inhibited gastric acid output.

Sleep Patterns and Gastric Acid Secretion in Duodenal Ulcer Disease

Five normal volunteers and five patients with duodenal ulcer (DU) disease were studied for five consecutive nights. All subjects underwent placement of a nasogastric tube, continuous collection of gastric juice, and continuous electroencephalographic monitoring of sleep. Gastric juice was collected in 20-minute samples by remote suction (Gomco). Blood samples were drawn every 20 minutes on the third night via an indwelling venous needle. Results showed no significant correlations between the sleep variables and the gastric acid secretion measures or between the sleep variables and serum gastrin levels. Acid secretion decreased from hour 1 to hour 2 in controls and in patients with inactive DU disease, while it increased in patients with active DU disease. Each subject had at least one night of recording in which continuous gastric secretion was less than 0.1 mEq per 20-minute sample. It appears unlikely that the gastric discomfort of DU patients can be attributed to acid hypersecretion triggered by rapid eye movement sleep.

Commentary: Ingestion of Asbestos

Several papers at this conference have dealt with studies of ingestion of asbestos in one form or the other. In one experiment, following asbestos ingestion, a gastric ulcer with an asbestos fiber perforating it was observed. One investigator did not find any significant pathology in the gastrointestinal tract with ingestion of asbestos, and some other workers found few particles here and there. I suggest that one of our most urgent needs is a proper and suitable choice of an experimental animal. In my opinion, the rat is one of the animals that should not be used. The simple reason is that half of the rat's stomach is lined by squamous epithelium and therefore does not simulate the human stomach. Dr. Shay from the United States (1) has been using rats to produce gastric ulcers which are not at all similar to those found in humans. The ulcers developed in rumenal mucosa which is lined by squamous epithelium. A second difficulty is collection of gastric juice. I do not know of much work that has been done with small intestine-or for that matter, with cecum and colon. I think that the monkey is a difficult animal to deal with. The fact that it is vegetarian also presents difficulties. You always find some food particles in the stomach-there is always some roughage left over. Therefore, if we have to do work on stomach or for that matter on intestine, we should not use monkeys. Now let us take the rabbit. Twenty years ago, I did some experiments on rabbits. I kept them without food for 4 days, put them on water and after 3 or 4