Motonobu Murakami

Contact Electrode Method in Hydrogen Gas Clearance Technique: A New Method for Determination of Regional Gastric Mucosal Blood Flow in Animals and Humans

A method was developed that was capable of measuring regional gastric mucosal blood flow in animals and humans. The method is based on the clearance of hydrogen gas from mucosal tissue as measured by a newly devised electrode that is placed in contact with gastric mucosa. The structure of the electrode was such that an insulated platinum spring with a tapered active tip was attached to a lead of suitable flexibility and rigidity. The method yielded reliable values of regional gastric mucosal blood flow, 93.5 ± 26.4 and 52.7 ± 16.1 ml/min · 100 g (mean ± SD) in the antrum and corpus of the glandular stomach of anesthetized rats respectively. Desaturation of hydrogen gas was monoexponential by our method, whereas it was multiexponential in most cases when a commercially available wire electrode was inserted through the mucosal layer. Some hydrogen gas escape into the gastric lumen was observed causing an overestimation of regional gastric mucosal blood flow when the stomach was inflated with air (10.5 ± 8.9 ml/min·100 g) or perfused (3.6 ± 2.9 ml/min 100 g, mean ± SD). Regression analysis demonstrated a highly significant linear correlation between aminopyrine clearance and blood flow measured by the contact electrode method in the pentagastrin stimulated state (r = 0.935, p

Products of neutrophil metabolism increase ammonia-induced gastric mucosal damage

Recent studies have indicated that ammonia is involved in the pathophysiology ofHelicobacter pylori-associated gastric mucosal damage.Helicobacter pylori-associated chronic active gastritis is characterized by an invasion of neutrophils. We investigated the interrelationship among hypochlorous acid (oxidant produced by neutrophil), ammonia (product ofHelicobacter pylori urease), and monochloramine (product of ammonia and hypochlorous acid) in the development of gastric mucosal damage in rats. Gastric mucosal lesions were produced by exposure of the gastric mucosa to ammonia, urea with urease, or urea withHelicobacter pylori in rats subjected to ischemia. Pretreatment with taurine (scavenger of hypochlorous acid) or antineutrophil serum significantly attenuated gastric mucosal lesions induced by the above test agents. Ammonia-induced gastric mucosal lesions were exacerbated in the presence of hypochlorous acid with concomitant generation of monochloramine. These results suggest that the ammonia, hypochlorous acid, and monochloramine triad may be important inHelicobacter pylori-mediated gastric mucosal damage.

Cerebral Correlates of the Progression Rate of the Cognitive Decline in Probable Alzheimer’s Disease

Objective: To evaluate the possible relation between the rate of cognitive deterioration in patients with probable Alzheimer’s disease (AD) and the distribution pattern of neural dysfunction. Methods: The regional cerebral blood flow (rCBF) was measured in rapidly and slowly progressing groups of AD patients using single-photon emission computed tomography and was compared between the groups. While controlling for demographic and clinical factors that could be associated with the stage and prognosis of the illness, the deterioration rate of the Mini Mental State Examination (MMSE) score was significantly greater in the rapidly progressing group than that in the slowly progressing group. Results: The rCBF in the right posterodorsal, anterior and superior prefrontal cortices and the inferior parietal cortex was significantly lower in the rapidly progressing patients. Moreover, lower perfusion in these regions correlated significantly with rapid deterioration in the MMSE. Conclusions: These findings suggest that the rCBF values in these cortical regions could be useful in predicting which AD patients will show a relatively rapid cognitive decline.

Gastric ammonia has a potent ulcerogenic action on the rat stomach

BACKGROUND The pathophysiological mechanism by which Helicobacter pylori induces mucosal injury has not been clarified. The aim of this study was to investigate the role of urea, urease, and ammonia in rat gastric mucosal lesions using an ex vivo chamber model. METHODS Two groups of rats, normotensive rats and those subjected to ischemia, were studied. The gastric mucosa was examined histologically and macroscopically, and the transmucosal potential difference was measured. RESULTS Instillation of urea into the stomach generated ammonia in the presence of urease. The amount of ammonia was increased depending on the concentration of urea and was closely associated with the severity of the histological lesions. The exposure of the stomach to 15-60 mmol/L ammonium hydroxide induced both a reduction in transmucosal potential difference and microscopic damage to the gastric mucosa in normotensive rats. Moreover, 15-60 mmol/L ammonium hydroxide produced severe macroscopic gastric lesions in the rats subjected to ischemia. CONCLUSIONS These results show that ammonia is deleterious to the gastric mucosa and suggest the importance of urea, urease, and ammonia in the pathophysiology of gastric diseases in H. pylori-infected patients.

Regional Cerebral Blood Flow Abnormalities in Nondemented Patients With Memory Impairment

Background. Patients with objective evidence of memory impairment have been considered to be at risk for developing Alzheimers disease (AD). However, little is known about patterns of regional cerebral blood flow abnormalities and their prognostic significance in these patients. Methods. The authors retrospectively studied 28 nondemented subjects with memory loss and investigated patterns of blood flow abnormalities on single photon emission computed tomography (SPECT). Results. The patients were followed up for more than 2 years; during follow‐up, 14 patients (50%) developed AD. The onset of memory impairment in patients who progressed to AD was significantly earlier than in those who remained in a nondemented condition. SPECT data from the initial evaluation were analyzed by region of interest analysis and statistical parametric mapping. Interestingly, both groups of patients shared hypoperfusion in the medial temporal regions and the posterior cingulate. In addition to these regions, significant blood flow reduction in the parietal and anterior cingulate cortices was detected in patients who progressed to AD. Conclusions. These results demonstrate that (1) subjects with an earlier onset of memory loss have an increased risk for developing AD, (2) SPECT can be useful for distinguishing subjects with memory loss who will rapidly progress to AD from those who will not, and (3) perfusion impairment typical of AD was evident even in subjects with memory impairment who remained nondemented.

Generation of Ammonia and Mucosal Lesion Formation Following Hydrolysis of Urea by Urease in the Rat Stomach

We examined the morphological changes in gastric mucosa and the generation of ammonia after exposure of the rat stomach to urea in the presence of urease, in attempts to investigate a pathophysiological role of urea, urease, and ammonia system in gastric ulcer diseases. Exposure of the stomach for 20 min to 2 ml urea (0.025–0.2%) together with urease (100 IU) induced histological damages in a concentration-related manner. Either urea or urease alone did not induce any histological change in the mucosa. Instillation of urea into the stomach generated ammonia in the presence of urease; the amount of ammonia was increased depending on the concentration of urea, and was closely associated with the severity of histological damage. The exposure of the stomach to ammonia (NH4OH: 0.01–0.1%) also produced histological damages in the gastric mucosa in a concentration-related manner. The characteristics of injury induced by 0.5–1.0% ammonia were stasis of microcirculation, disruption of the surface epithelial cells, and necrosis of the mucosa. These results demonstrated that ammonia generated from the hydrolysis of urea by urease in the stomach causes damages in the gastric mucosa.

Bovine milk inhibits both adhesion of Helicobacter pylori to sulfatide and Helicobacter pylori-induced vacuolation of Vero cells

Adhesion of Helicobacter pylori to gastricmucosal cells is an initial important step incolonization and infection. To study adhesion, weinvestigated whether milk inhibits the adhesion ofHelicobacter pylori to sulfatide, an acidicglycosphingolipid that exists in human gastric mucosaand to which Helicobacter pylori adheres. As a measureof functional significance, we also studied whether milkinhibits Helicobacter pylori-induced vacuolation of Verocells. We used sulfatide-coated polystyrene plates andstudied the effect of bovine milk on the adhesion ofHelicobacter pylori to sulfatide. We used Vero cells for Helicobacter pylori -inducedvacuolation. Bovine milk 100- to 200-fold dilutedsignificantly inhibited both adhesion of Helicobacterpylori to sulfatide and Helicobacter pylori-inducedvacuolation in Vero cells. Bovine milk significantlyinhibited adhesion of Helicobacter pylori to MKN-45cells and Lewis b antigen-coated polystyrene plates. Inaddition, these results suggest that bovine milkcontains active substances that inhibit both adhesion ofHelicobacter pylori to mucosa and vacuole formation.Bovine milk may have a protective effect on the gastricmucosa in Helicobacter pylori-associatedgastritis.

Therapeutic effects of lansoprazole on peptic ulcers in elderly patients

We studied the effects of lansoprazole on ulcer healing and Helicobacter pylori infection in elderly patients with peptic ulcers. In a group of 24 patients with gastric ulcers, the H. pylori infection rate was 100%. In the course of gastric ulcer healing with famotidine or lansoprazole alone, the H. pylori infection showed no signs of decline. The ulcer healing rates after 8 weeks were similar between the H2-receptor antagonist famotidine (73%), and the proton pump inhibitor lansoprazole (82%). When eradication of H. pylori infection was attempted by concomitant administration of lansoprazole and amoxicillin 500 mg b.i.d. for 2 weeks, the eradication rate was 33% in the group given lansoprazole 30 mg q.d. plus ampicillin 500 mg b.i.d., whereas it was 77% in the group given lansoprazole 30 mg b.i.d. plus ampicillin 500 mg b.i.d. Lansoprazole is considered to be a useful agent for the treatment of patients with peptic ulcers and H. pylori infection and its effectiveness in H. pylori eradication is improved by b.i.d. administration along with ampicillin.

Link between Helicobacter pylori-associated gastritis and duodenal ulcer.

We examined the interrelationships among the degree of fundic mucosal atrophy, the prevalence ofHelicobacter pylori in the gastric antrum, the gastric juice, and the duodenum with and without gastric metaplasia, in 20 duodenal ulcer patients and 20 non-duodenal ulcer patients. The detection rates ofH. pylori in the antrum, the gastric juice, and the duodenum were significantly higher in duodenal ulcer patients (80%, 65%, and 60%) than in non-duodenal ulcer subjects (50%, 20%, and 5%). The frequency ofH. pylori was significantly lower in the gastric juice (30%) and the duodenum (10%) in non-duodenal ulcer patients with antralH. pylori, compared with those in duodenal ulcer patients with antralH. pylori. All of seven patients with both gastric metaplasia andH. pylori infection in the duodenum had duodenal ulcer, whereas only 1 of 14 patients without either gastric metaplasia orH. pylori infection in the duodenum had duodenal ulcer. There was normal or mild atrophic mucosa in the fundus of duodenal ulcer patients withH. pylori in the antrum, whereas moderate or severe atrophic mucosa in non-duodenal ulcer patients withH. pylori gastritis. These results suggest that the preserved fundic mucosa, gastric metaplasia in the duodenum, and a greater load ofH. pylori to the duodenum through the gastric juice may be prerequisites for the formation of duodenal ulcers.

Sulfamethizole capsule method. A new method for assessing gastric emptying of solids.

We have developed a new method that is capable of assessing gastric emptying in humans. This method is based on the rapid absorption of sulfamethizole in the upper small intestine. Sulfamethizole capsules are gelatin capsules that are filled with a solid composed of egg albumin and sulfamethizole. After subjects ingested of 15 capsules with ham and bread, blood concentrations of sulfamethizole were measured and the areas under the sulfamethizole concentration-time curve (AUC) were calculated as an index of gastric emptying. After ingestion of99mTc-labeled sulfamethizole capsules, there was a statistically significant correlation between the percentage of radioactivity remaining in the stomach at 120 min and AUC for 120 min (r=−0.82,P<0.01). This method yielded a reliable value for gastric emptying of a solid meal as estimated by AUC. This method can be considered safe and is easily applicable to human subjects for assessment of gastric emptying.