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Biomedical subjects

T Kitahora

Publications and source records attributed to T Kitahora.

At least 19 recordsLinked to original sources

Proton pump inhibitor modifies inflammatory reaction in human gastric mucosa infected by Helicobacter pylori.

AIM: To examine whether proton pump inhibitors modify the production of oxygen-derived free radicals and related cytokines in the human gastric mucosa infected with H. pylori. METHODS: Thirty-four H. pylori-positive peptic ulcer patients (23 gastric ulcer, 11 duodenal ulcer) were enrolled. Biopsy tissue samples were obtained endoscopically from the antrum and corpus. Tissue content of neutrophil myeloperoxidase (myeloperoxidase) and IL-8 was measured by ELISA. Mucosal production of oxygen-derived free radical was measured using luminol-dependent chemiluminescence (ChL). A proton pump inhibitor (either lansoprazole 30 mg, omeprazole 20 mg, or rabeprazole 10 mg) was administered daily by mouth to all patients for 8 weeks. Endoscopic examination was then repeated, and biochemical analysis was performed. RESULTS: Antral myeloperoxidase decreased significantly after proton pump inhibitor treatment (5.23 +/- 7.00-2.76 +/- 5.11 ng/mg, P < 0.02), but corpus myeloperoxidase was unchanged. IL-8 was also modified by proton pump inhibitors and these changes were parallel to those of myeloperoxidase. Corpus ChL was significantly increased from 88.5 +/- 69.8-159 +/- 172 counts/10 s/mg after proton pump inhibitor treatment, whereas antrum ChL was not altered. H. pylori infection rate was decreased in the antrum as well as the corpus. CONCLUSIONS: Proton pump inhibitor treatment stimulated oxygen-derived free radical production in the corpus mucosa.

Adult↗

Treatment with a proton pump inhibitor promotes corpus gastritis in patients with Helicobacter pylori-infected antrum-predominant gastritis.

BACKGROUND: Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis. AIM: To quantitatively investigate the effect of a proton pump inhibitor on the mucosal neutrophil reaction. METHODS: Forty-six H. pylori-infected patients (17 duodenal ulcer, 29 gastric ulcer) were enrolled. During endoscopic examination, biopsy samples were obtained from the antrum and the corpus. The tissue content of neutrophil myeloperoxidase was measured by enzyme-linked immunoabsorbent assay, and H. pylori infection was histologically assessed. A proton pump inhibitor was administered orally for 8 weeks. RESULTS: In the patients as a whole, antral myeloperoxidase decreased significantly after proton pump inhibitor treatment, but corpus myeloperoxidase remained largely unchanged. In duodenal ulcer patients, myeloperoxidase significantly decreased in the antrum, but increased in the corpus. In gastric ulcer patients, a significant reduction was observed in antral myeloperoxidase, but corpus myeloperoxidase remained unchanged. In the antral myeloperoxidase > corpus myeloperoxidase subgroup (n=24), antral myeloperoxidase significantly decreased, whereas corpus myeloperoxidase increased. No changes were observed at either site in the corpus myeloperoxidase > antral myeloperoxidase subgroup. Histology showed that the antral bacterial load of H. pylori decreased in all subgroups, but that it was mostly unchanged in the corpus. CONCLUSIONS: Proton pump inhibitor treatment stimulated the neutrophil reaction in the corpus mucosa of duodenal ulcer patients and of patients in whom antral neutrophil accumulation was more predominant than that of the corpus. This phenomenon may not be caused by increased bacterial density.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Anorexia nervosa with severe liver dysfunction and subsequent critical complications.

A twenty-year-old woman with anorexia nervosa (body mass index=11) suffered from severe liver dysfunction (aspartate aminotransferase 5,000 IU/l, alanine aminotransferase 3,980 IU/l, prothrombin time 32%), hypoglycemia (serum glucose 27 mg/dl), and pancreatic dysfunction (amylase 820 IU/l, lipase 558 IU/l). She fell into a depressive state with irritability, which was not improved by intravenous glucose. Despite treatment with plasmapheresis for the liver dysfunction, she subsequently developed pulmonary edema, acute renal failure, gastrointestinal bleeding, and disseminated intravascular coagulation. Hemodialysis, mechanical ventilation and drug therapy including prednisolone, prostaglandin E1, and branched-chain amino acid, improved her critical condition. In this case, malnutrition may have been the cause for the liver dysfunction and subsequent complications.

Acute Kidney Injury↗

Gastric urease activity is inversely associated with the success of treatment for Helicobacter pylori: effect of sofalcone.

Eradication therapy for Helicobacter pylori (H. pylori) has been established. However, the physiological factors influencing the success of treatment remain unclear. The aim of this study was to analyze these factors and to evaluate the efficacy of sofalcone on H. pylori eradication therapy. Forty-four H. pylori-infected and peptic ulcer patients were enrolled in this study. Twenty-seven patients were treated with lansoprazole (LPZ, 30 mg o.d. for 1-8 weeks) and amoxicillin (AMPC, 500 mg q.i.d, 1-2 weeks), followed by 8 weeks of treatment with famotidine (FAM, 20 mg o.d.). Moreover, sofalcone (SOF, 100 mg t.i.d) was administered to 17 patients throughout the therapeutic period. Endoscopic and serologic evaluations and the urea breath test (UBT) were performed before therapy. At the endoscopic examination, mucosal samples were biopsied and then tissue myeloperoxidase (MPO) content, an index of neutrophil infiltration was measured. Cure of H. pylori infection was determined 8 weeks after the cessation of LPZ. This eradication regimen afforded an overall cure rate of 63.0% (17/27) without SOF and 76.5% (13/17) with SOF. In the control group, treatment success was inversely associated with pre-UBT value (gastric urease activity), whereas this association was not observed in the SOF group. Furthermore, in the patients exhibiting a high preUBT value (>40%), a twofold higher eradication rate was obtained by the administration of SOF. In patients who were successfully eradicated, mucosal MPO level was slightly higher than those of unsuccessful cases, whereas there was no significant association with serum pepsinogen (PG I, PG II) concentration and its ratio (PG I/PG II). These results suggest that a low UBT value is a factor predicting treatment success. SOF administration may improve the eradication rate, especially in the high-UBT subgroup.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Augmented levels of gastric mucosal leucocyte activation by infection with cagA gene-positive Helicobacter pylori.

The possession of the cytotoxin-associated gene (cagA) of Helicobacter pylori is thought to be highly associated with peptic ulcer disease. However, the pathogenic role of cagA is still unknown. We have emphasized the importance of the interrelationship between H. pylori-derived ammonia and oxygen radicals from infiltrated leucocytes. The aim of the present study was to explore the relationship between oxygen radical production and H. pylori strain diversity based on cagA possession. An endoscopic examination and gastric mucosal biopsy were performed in 30 H. pylori-infected patients with gastric ulcer. Myeloperoxidase (MPO) content and the luminol-dependent chemiluminescence value in the biopsied gastric specimens were measured as an index for leucocyte infiltration and oxygen radical production. From the precipitates of cultured bacterial isolates of biopsied specimens, bacterial DNA was purified and analysed by polymerase chain reaction to characterize the possession of cagA. While all patients had ureC-positive strains, 22 had cagA-positive and eight had cagA-negative strains. In patients with cagA-positive strains, MPO contents as well as chemiluminescence values in the gastric corpus were significantly higher than those in patients with cagA-negative strains. Gastric mucosal leucocyte recruitment and activation are suggested to be enhanced by cagA gene-positive H. pylori infection.

Adult↗

Rebamipide attenuates gastric microcirculatory disturbances in the early period after thermal injury in rats.

In our previous study we showed that rebamipide attenuated gastric erosions and active oxygen species released only from the gastric mucosa and not from circulating leukocytes after thermal injury. This study was designed to examine whether rebamipide affects the potential of active oxygen generation from circulating leukocytes, and attenuates microcirculatory disturbance caused by thermal injury to skin. Rats were anesthetized and a 30% full skin-thickness dorsal burn was inflicted. Microvascular images and leukocytes were observed using in vivo microscopy. Endothelial damage was assessed by monastral blue B deposits. Active oxygen species were measured by the chemiluminescence method. Rebamipide (100 mg/kg) decreased leukocyte rolling and monastral blue B deposits in venules but did not improve arteriolar contractions 15 min after thermal injury. These results suggest that rebamipide preserves gastric microcirculation possibly through inhibition of leukocyte adhesion and endothelial damage caused by thermal injury to skin.

Alanine↗

Characteristics of Helicobacter pylori strains isolated from patients with different gastric diseases.

The pathogenesis of chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis is considered to be related to infection by Helicobacter pylori. The purpose of this study was to investigate the characteristics of H. pylori strains isolated from patients with various gastric diseases. Fifty strains of H. pylori were clinically isolated at Keio University Hospital and were assessed for (i) vacuolating cytotoxin (VT) production, by cytotoxic assay using rabbit kidney (RK) 13 cells; (ii) the expression of cytotoxin associated gene (cagA), by polymerase chain reaction; and (iii) motility on a semi-solid plate. Positivity for VT production by H. pylori strains isolated from patients with chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, was 100%, 89%, 92%, 100%, and 60%, respectively. There was no significant difference in the incidence of positivity for cagA among the strains isolated from different gastric diseases. Swarming distances, which indicate motility of H. pylori strains, were 12.7, 13.2, 12.8, 16.6 and 9.2mm in strains from chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, respectively, with H. pylori isolated from remnant gastritis showing significantly less motility than H. pylori isolates from other diseases. There were no significant differences in VT production and cagA positivity among the H. pylori strains.

Animals↗

Active oxygen species in formation of acute gastric mucosal lesions induced by thermal injury in rats.

Active oxygen species generated by circulating leukocytes and released from the gastric mucosa were measured in the process of acute gastric mucosal lesion formation after thermal injury in rats. Alterations of luminol-dependent chemiluminescence activities generated by leukocytes obtained from the gastric vein and the inferior vena cava were approximately same. A decrease in chemiluminescence activity 15 min after thermal injury and a significant increase in chemiluminescence activity 5 hr after thermal injury were observed in leukocytes from both veins. From 15 min to 12 hr after thermal injury, luciferin-dependent chemiluminescence activities were significantly higher than that of the control group. Oral administration of rebamipide resulted in decreased mucosal lesion formation. Rebamipide, an antiulcer agent that protects the mucosa from damage in various animal models decreased chemiluminescence activities only released from the gastric mucosa but not from circulating leukocytes. These results suggest that two different pathways of active oxygen species formation may exist in the pathogenesis of acute gastric mucosal lesions after thermal injury.

Acute Disease↗

Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan.

Epidemiological studies of ulcerative colitis (UC) have been conducted once every year since 1973 in Japan. The number of participating hospitals in 1429 and they are distributed throughout Japan. A total number of 10819 patients diagnosed with UC have been registered, including 197 patients with a positive family history. In this present study, genetic or environmental factors that may be operative in the development of UC were investigated. After 1966, the annual incidence of UC increased rapidly, to a peak in 1974, tending to remain at the same level since 1975. Since 1975, the daily intake of dairy products and meat increased, paralleling the increase in the incidence of UC. The trends of the increase in the incidence of UC and the increase in the daily intake of meat were very similar. The tendency for UC to occur in families was high, especially in first-degree relatives, and the age at onset of UC in patients where there was familial occurrence was younger. There was no difference in HLA antigens between UC patients with familial occurrence and the unaffected relatives studied. It is presumed that not only genetic factors but also environmental factors may be operative in the development of UC.

Adolescent↗

[Quantitative evaluation of liver function with 99mTc-GSA scintigraphy using extraction index].

Extraction index (EI5) was introduced to evaluate liver function quantitatively with 99mTc-GSA (GSA) scintigraphy, and it was compared with conventional indices; receptor index (LHL15) and clearance index (HH15). EI5 is expressed as following equation: EI5 = (L5 - L3)/(H3 + H5) * PH/PL where L3, L5: counts at 3 or 5 minutes after the injection in the liver ROI, respectively, H3, H5: counts at 3 or 5 minutes in the heart ROI, respectively; PL, PH: numbers of pixels in the liver- and heart-ROI, respectively. We performed GSA scintigraphy in 40 patients with liver dysfunction and calculated values of the indices. Good correlations were observed between EI5 and liver function tests. Correlation coefficients were almost equal to or higher than those between conventional parameters and liver functional tests. EI5 was thought to be a practical index, and it could be calculated in a short time without aid of computer. Evaluation of local liver function may be possible, because EI5 was corrected with numbers of pixels in the liver- and heart-ROI; which was not considered in the conventional parameters.

Adult↗

Ischemia-reperfusion induced gastric mucosal microcirculatory alterations in the rat.

The aim of this study was to determine the gastric microcirculatory alterations occurring during reperfusion after a period of ischemia and the possible role of oxyradicals in the microcirculatory disturbance. An in vivo microscopy technique was used to observe the superficial mucosal blood flow during reperfusion. After reperfusion, mucosal blood flow resumed quickly and then slowed with eventual cessation of flow. Thirty minutes of ischemia followed by reperfusion resulted in cessation of flow in 50 +/- 4% and 81 +/- 8%, of the capillaries in the microscopic field at 15 and 30 min, respectively, after reperfusion. During this mucosal microcirculatory change, numerous white thrombi were observed flowing in the mucosal microvessels. In rats pretreated with allopurinol to inhibit oxyradical formation, blood flow was maintained to a significant and markedly greater extent. Study of the submucosal microvasculature after reperfusion revealed a marked delay in transit of a fluorescein-albumin bolus from terminal submucosal arterioles through the mucosal microvasculature and back to submucosal collecting venules. Submucosal vascular diameter change could not explain the altered mucosal blood flow. These findings indicate that there is marked slowing and cessation (in many microvessels) of gastric mucosal blood flow during reperfusion after a period of ischemia, and that the obstruction to flow occurs in the mucosal microvessels. The results of the study with allopurinol suggest that oxygen-derived free radicals generated by xanthine oxidase may play a major role in the genesis of this gastric mucosal microcirculatory disturbance.

Allopurinol↗

Effects of serine protease inhibitors on oxyradical burst from phagocytizing neutrophils--analysis by chemiluminescence counting and its microscopic imaging.

Reaction difference of oxyradical generation and luminol-dependent photoemission of zymosan- and phorbol ester-treated neutrophils were investigated using a conventional photomultiplier and ultrasensitive photonic imaging technique. Zymosan-treated cells released a concentrated photonic burst corresponding to the cellular distribution. In contrast, phorbol ester-treated cells produced a negligible level of photoemission, and the additional application of Ca2+ ionophore enhanced the photonic burst, which was gradually spread out into extracellular space. Serine protease inhibitors did not attenuate PMA-induced chemiluminescence but did attenuate zymosan-induced chemiluminescence. This suggests the involvement of serine protease in the respiratory burst of phagocytizing neutrophils.

Free Radicals↗

Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease.

Chemiluminescence (CL) analysis of monocytes and polymorphonuclear cells (PMNs) was performed on 13 patients with Crohn's disease (CD) and 10 healthy volunteers. The percentages of monocyte populations in mononuclear cells obtained from the patients with CD were greater than those from the healthy volunteers, but the numbers of PMNs were not different between the two groups. The peak level of phorbol myristate acetate (PMA)-induced CL activity generated by diluted whole blood from the patients with CD was more significantly elevated than that from the healthy volunteers, whereas the peak levels of opsonized zymosan-induced CL activity did not differ between the two groups. In monocytes, the peak levels of both PMA- and opsonized zymosan-induced CL activity were significantly higher in the patients with CD than in the healthy volunteers. CL in PMNs, however, showed no significant difference between CD and controls. It is suggested that monocytes of CD have a large capacity to generate active oxygen species. The present study suggests that excessive active oxygen species released by monocytes and perhaps macrophages may play an important role in formation of the intestinal lesions in CD.

Adult↗

Gastric mucosal blood flow and acid secretion in portal hypertensive rats.

The purpose of this study was to examine gastric mucosal blood flow, measured by hydrogen gas clearance, and acid secretion in portal hypertensive rats. Chronic portal hypertension was induced by a two-stage complete portal vein occlusion procedure. Basal gastric mucosal blood flow was significantly higher in portal hypertensive rats than in sham-operated rats, but there was no difference in basal acid output. In response to administration of pentagastrin, there was the expected rise in both acid secretion and blood flow in sham-operated rats, but in portal hypertensive rats there was a significantly lower increase in acid output and no change in blood flow. In portal hypertensive rats pretreated with indomethacin to inhibit endogenous prostaglandin generation, both basal blood flow and acid secretion--and their response to pentagastrin administration--were the same as in non-indomethacin-treated sham-operated rats. We conclude that in portal hypertensive rats there is an increased gastric mucosal blood flow and an impaired acid output response to pentagastrin stimulation, and these changes appear to be mediated by an increase in endogenous prostaglandin.

Animals↗

Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation.

The effect of topically applied aspirin or HCl, or both, on gastric mucosal blood flow was studied by in vivo microscopy in the rat. Ten minutes after the topical application of 20 mM aspirin in 50 mM HCl, red blood cell flow ceased and red blood cells were no longer present in the superficial mucosal microvessels in 76.8% +/- 7.7% of the microscopic field. Hydrochloric acid (50 mM) alone caused this effect in only 12.8% +/- 12.8% of the field, whereas 20 mM aspirin alone had no effect. During this microcirculatory change, white thrombi were observed flowing through mucosal microvessels. Later, mucosal hemorrhages developed in areas where flow had ceased. Study of the submucosal microcirculation suggested that high concentrations of HCl are responsible for thrombus formation and low concentrations of HCl for submucosal arteriolar constriction. These results suggest that aspirin-induced acid back-diffusion causes thrombus formation in mucosal microvessels and submucosal arteriolar constriction. These microcirculatory changes might play a causative role in the cessation of mucosal blood flow, mucosal injury, and focal hemorrhage.

Animals↗

Increased respiratory burst of leukocytes in inflammatory bowel diseases--the analysis of free radical generation by using chemiluminescence probe.

Respiratory burst of leukocytes was determined in Crohn's disease, intestinal Behçet's disease and ulcerative colitis by using chemiluminescence assay. Oxygen-derived free radicals of monocytes in Crohn's disease and those of polymorphonuclear leukocytes in intestinal Behçet's disease were significantly raised as compared with those of controls. In ulcerative colitis, respiratory burst activities of both polymorphonuclear leukocytes and monocytes were found to be highly associated with the disease activities. These results suggest that active oxygen species from leukocytes may participate in the formation of intestinal mucosal lesions in inflammatory bowel diseases via auto-oxidative process.

Adult↗