Periodontal tissue engineering by nano beta-tricalcium phosphate scaffold and fibroblast growth factor-2 in one-wall infrabony defects of dogs.

BACKGROUND AND OBJECTIVE: Nanoparticle bioceramics are being investigated for biomedical applications. We fabricated a regenerative scaffold comprising type I collagen and beta-tricalcium phosphate (ß-TCP) nanoparticles. Fibroblast growth factor-2 (FGF-2) is a bioeffective signaling molecule that stimulates cell proliferation and wound healing. This study examined the effects, on bioactivity, of a nano-ß-TCP/collagen scaffold loaded with FGF-2, particularly on periodontal tissue wound healing. MATERIAL AND METHODS: Beta-tricalcium phosphate was pulverized into nanosize particles (84 nm) and was then dispersed. A nano-ß-TCP scaffold was prepared by coating the surface of a collagen scaffold with a nanosize ß-TCP dispersion. Scaffolds were characterized using scanning electron microscopy, compressive testing, cell seeding and rat subcutaneous implant testing. Then, nano-ß-TCP scaffold, nano-ß-TCP scaffold loaded with FGF-2 and noncoated collagen scaffold were implanted into a dog one-wall infrabony defect model. Histological observations were made at 10 d and 4 wk postsurgery. RESULTS: Scanning electron microscopy images show that TCP nanoparticles were attached to collagen fibers. The nano-ß-TCP scaffold showed higher compressive strength and cytocompatibility compared with the noncoated collagen scaffold. Rat subcutaneous implant tests showed that the DNA contents of infiltrating cells in the nano-ß-TCP scaffold and the FGF-2-loaded scaffold were approximately 2.8-fold and 3.7-fold greater, respectively, than in the collagen scaffold. Histological samples from the periodontal defect model showed about five-fold greater periodontal tissue repair following implantation of the nano-ß-TCP scaffold loaded with FGF-2 compared with the collagen scaffold. CONCLUSION: The ß-TCP nanoparticle coating strongly improved the collagen scaffold bioactivity. Nano-ß-TCP scaffolds containing FGF-2 are anticipated for use in periodontal tissue engineering.

Semaphorin 3A Induces Odontoblastic Phenotype in Dental Pulp Stem Cells.

In cases of pulp exposure due to deep dental caries or severe traumatic injuries, existing pulp-capping materials have a limited ability to reconstruct dentin-pulp complexes and can result in pulpectomy because of their low potentials to accelerate dental pulp cell activities, such as migration, proliferation, and differentiation. Therefore, the development of more effective therapeutic agents has been anticipated for direct pulp capping. Dental pulp tissues are enriched with dental pulp stem cells (DPSCs). Here, the authors investigated the effects of semaphorin 3A (Sema3A) on various functions of human DPSCs in vitro and reparative dentin formation in vivo in a rat dental pulp exposure model. Immunofluorescence staining revealed expression of Sema3A and its receptor Nrp1 (neuropilin 1) in rat dental pulp tissue and human DPSC clones. Sema3A induced cell migration, chemotaxis, proliferation, and odontoblastic differentiation of DPSC clones. In addition, Sema3A treatment of DPSC clones increased ß-catenin nuclear accumulation, upregulated expression of the FARP2 gene (FERM, RhoGEF, and pleckstrin domain protein 2), and activated Rac1 in DPSC clones. Furthermore, in the rat dental pulp exposure model, Sema3A promoted reparative dentin formation with dentin tubules and a well-aligned odontoblast-like cell layer at the dental pulp exposure site and with novel reparative dentin almost completely covering pulp tissue at 4 wk after direct pulp capping. These findings suggest that Sema3A could play an important role in dentin regeneration via canonical Wnt/ß-catenin signaling. Sema3A might be an alternative agent for direct pulp capping, which requires further study.

Clinical outcomes of tracheoesophageal diversion for intractable aspiration.

OBJECTIVES: The purpose of the present study was to examine the clinical outcomes of using tracheoesophageal diversion for preventing intractable aspiration. METHOD: We retrospectively reviewed 25 patients who underwent tracheoesophageal diversion from 2003 to 2009 at our hospital (median age, 25 years; range, 0-78 years). End-to-side anastomosis was used in 16 cases and side-to-side anastomosis was used in 9. RESULTS: The average operative time was 141 minutes for end-to-side anastomosis and 191 minutes for side-to-side anastomosis. Peri-operative complications were observed in only two (8 per cent) cases: one with infection and one with haematoma. No fistulas were observed. Aspiration was prevented in all cases, but the nutritional route depended on the swallowing function of the patient. Oral feeding was the main nutritional route after surgery in only four patients (16 per cent). CONCLUSION: This procedure is well suited to patients who lack speech communication and are at high risk of aspiration.

Bone augmentation using a highly porous PLGA/ß-TCP scaffold containing fibroblast growth factor-2.

BACKGROUND AND OBJECTIVE: Beta-tricalcium phosphate (ß-TCP), a bio-absorbable ceramic, facilitates bone conductivity. We constructed a highly porous three-dimensional scaffold, using ß-TCP, for bone tissue engineering and coated it with co-poly lactic acid/glycolic acid (PLGA) to improve the mechanical strength and biological performance. The aim of this study was to examine the effect of implantation of the PLGA/ß-TCP scaffold loaded with fibroblast growth factor-2 (FGF-2) on bone augmentation. MATERIAL AND METHODS: The ß-TCP scaffold was fabricated by the replica method using polyurethane foam, then coated with PLGA. The PLGA/ß-TCP scaffold was characterized by scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction, compressive testing, cell culture and a subcutaneous implant test. Subsequently, a bone-forming test was performed using 52 rats. The ß-TCP scaffold, PLGA-coated scaffold, and ß-TCP and PLGA-coated scaffolds loaded with FGF-2, were implanted into rat cranial bone. Histological observations were made at 10 and 35 d postsurgery. RESULTS: SEM and TEM observations showed a thin PLGA layer on the ß-TCP particles after coating. High porosity (> 90%) of the scaffold was exhibited after PLGA coating, and the compressive strength of the PLGA/ß-TCP scaffold was six-fold greater than that of the noncoated scaffold. Good biocompatibility of the PLGA/ß-TCP scaffold was found in the culture and implant tests. Histological samples obtained following implantation of PLGA/ß-TCP scaffold loaded with FGF-2 showed significant bone augmentation. CONCLUSION: The PLGA coating improved the mechanical strength of ß-TCP scaffolds while maintaining high porosity and tissue compatibility. PLGA/ß-TCP scaffolds, in combination with FGF-2, are bioeffective for bone augmentation.

Application of collagen hydrogel/sponge scaffold facilitates periodontal wound healing in class II furcation defects in beagle dogs.

BACKGROUND AND OBJECTIVE: A three-dimensional scaffold may play an important role in periodontal tissue engineering. We prepared bio-safe collagen hydrogel, which exhibits properties similar to those of native extracellular matrix. The aim of this study was to examine the effect of implantation of collagen hydrogel/sponge scaffold on periodontal wound healing in class II furcation defects in dogs. MATERIAL AND METHODS: The collagen hydrogel/sponge scaffold was prepared by injecting collagen hydrogel, cross-linked to the ascorbate-copper ion system, into a collagen sponge. Class II furcation defects (of 5 mm depth and 3 mm width) were surgically created in beagle dogs. The exposed root surface was planed and demineralized with EDTA. In the experimental group, the defect was filled with collagen hydrogel/sponge scaffold. In the control group, no implantation was performed. Histometric parameters were evaluated 2 and 4 wk after surgery. RESULTS: At 2 wk, the collagen hydrogel/sponge scaffold displayed high biocompatibility and biodegradability with numerous cells infiltrating the scaffold. In the experimental group, reconstruction of alveolar bone and cementum was frequently observed 4 wk after surgery. Periodontal ligament tissue was also re-established between alveolar bone and cementum. Volumes of new bone, new cementum and new periodontal ligament were significantly greater in the experimental group than in the control group. In addition, epithelial down-growth was suppressed by application of collagen hydrogel. CONCLUSION: The collagen hydrogel/sponge scaffold possessed high tissue compatibility and degradability. Implantation of the scaffold facilitated periodontal wound healing in class II furcation defects in beagle dogs.

Root surface conditioning with bone morphogenetic protein-2 facilitates cementum-like tissue deposition in beagle dogs.

BACKGROUND AND OBJECTIVE: Modification of the root surface may play an important role in regenerating the periodontal attachment between the root and periodontal connective tissue. We speculated that bone morphogenetic protein (BMP) application to the root surface constructed a novel attachment by cementum-like hard tissue, although gingival connective tissue proliferated to the root surface. The aim of this study was to examine whether BMP-2 guided cementum-like tissue deposition on a BMP-conditioned root surface. MATERIAL AND METHODS: Root dentin on the buccal side of 24 teeth in four beagle dogs was surgically exposed. The denuded root dentin surfaces were demineralized with EDTA and washed with saline. Subsequently, 15 microL of BMP-2 solution (loading dose, 0.4 and 1.0 microg/microL) was applied to the root dentin surface. In the control roots, phosphate-buffered saline was applied to the root surface. Specimens were analyzed histologically 16 wk after surgery. RESULTS: Formation of cementum-like tissue was frequently observed on the BMP-2-conditioned root at the coronal portion. Cellular cementum-like tissue was separated from the original cementum and encapsulated with gingival connective tissue. Cementum-like tissue formation with BMP-2 at 1.0 microg/microL was significantly greater than that in the control roots and those with BMP-2 at 0.4 microg/microL. Downgrowth of the junctional epithelium in the 1.0 microg/microL BMP-2 group was significantly less than that in the control roots. CONCLUSION: Root dentin surface conditioning with BMP-2 stimulated cementum-like tissue formation and inhibited epithelial downgrowth.

Dentin resorption and cementum-like tissue formation by bone morphogenetic protein application.

BACKGROUND AND OBJECTIVE: Recent studies have shown that bone morphogenetic protein-2 (BMP-2) stimulates mineralization and osteoclast differentiation. Osteoclastic resorption by BMP-2 application may play an important role in the regulation of new cementum-like tissue formation on the dentin surfaces. Therefore, this study aimed to examine the effect of BMP-2 application on dentin resorption and cementum-like tissue formation at the dentin surfaces. MATERIAL AND METHODS: Seventy-two flat dentin blocks were prepared from rat roots and treated with 24% EDTA. Each block was assigned to group 0, group 100, or group 400, and immersed correspondingly in 0, 100, or 400 microg/ml BMP-2. The dentin blocks were then implanted into palatal connective tissue of rats, and specimens were prepared 2, 4 and 8 wk after surgery for histologic and histomorphometric analyses. RESULTS: BMP-2 caused a dose-dependent increase in dentin resorption by osteoclastic cells. New cementum-like tissue was randomly formed on parts of the nonresorbed and resorbed dentin surfaces in groups 100 and 400. Dentin resorption in groups 100 and 400 was significantly greater than group 0 (p < 0.01). However, at 8 wk, new cementum-like tissue formed in 41.8% of group 100, as compared with 16.2% of group 400 (p < 0.05). CONCLUSION: Dentin resorption was stimulated by a high dose of BMP-2, and cementum-like tissue was induced by a low dose of BMP-2, effectively suggesting that BMP-2 application, at an appropriate dose, to a dentin surface may enhance periodontal regeneration.

Dynamics of alpha and beta processes in thin polymer films: poly(vinyl acetate) and poly(methyl methacrylate).

Dynamics of thin films of poly(vinyl acetate) (PVAc) and poly(methyl methacrylate) (PMMA) have been investigated by dielectric relaxation spectroscopy in the frequency range from 0.1 Hz to 1 MHz at temperatures from 263 to 423 K. The alpha process, the key process of glass transition, is observed for thin films of PVAc and PMMA as a dielectric loss peak at a temperature T(alpha) in temperature domain with a fixed frequency. For PMMA, the beta process is also observed at a temperature T(beta). For PVAc, T(alpha) decreases gradually with decreasing thickness, and the thickness dependence of T(alpha) is almost independent of the molecular weight (Mw< or =2.4x10(5)). For PMMA, T(alpha) remains almost constant as thickness decreases down to a critical thickness dc, at which point it begins to decrease with decreasing thickness. Contrastingly, T(beta) decreases gradually as thickness decreases to dc, and below dc it decreases drastically. For both PVAc and PMMA, the broadening of the distribution of the relaxation times in thinner films is observed and this broadening is more pronounced for the alpha process than for the beta process. It is also observed that the relaxation strength is depressed as the thickness decreases for both the polymers.

Creutzfeldt-Jakob disease: serial changes on diffusion-weighted MRI.

We present serial changes on diffusion-weighted MRI (DWI) in a patient with Creutzfeldt-Jakob disease (CJD). DWI revealed serial changes of abnormal hyperintense lesions that had become more extensive and conspicuous with progression of neurologic findings, more sensitively than conventional MRI. In the late stage, disappearance of abnormal hyperintense lesions on DWI was observed. DWI proved to be particularly useful for monitoring the progression of CJD.

[Radiofrequency ablation of rabbit liver: correlation between CT findings and pathological findings].

The purpose of this study was to present the time-related imaging findings and correlative pathological findings of irradiated regions in the rabbit liver. RF ablation was carried out on 16 rabbit livers. Irradiated regions were imaged at 3 days, 4 weeks, and 12 weeks. At 3 days, the regions showed a two-zone structure on plain CT and peripheral enhancement on the arterial phase. The regions presented a three-zone structure on pathological study. At 4 weeks, peripheral enhancement had almost disappeared, and a two-zone structure obscured on plain CT. The CT findings reflected pathological changes after RF ablation.

Production of recombinant granulocyte colony-stimulating factor by knocking into the active immunoglobulin heavy chain gene locus in the hybridoma cell line.

The hybridoma cell line KM50 originally produces a monoclonal antibody at a concentration of approximately 40 mg ml(-1) in ascites. To investigate the possibility to apply this expression system to the production of useful proteins, the cDNA encoding human granulocyte colony-stimulating factor was inserted by homologous recombination into just downstream of the promoter of the active immunoglobulin heavy chain gene of KM50. Site directed integration of targeting DNAs resulted in the disruption of expression of the immunoglobulin heavy chain proteins with a frequency of 1 in 10 approximately 100 G418-resistance transfectants. One of the monoclonal antibody-deficient transfectants produced25 ng ml(-1) of granulocyte colony-stimulating factor in the supernatant of its cell culture the number of molecules of which corresponds to that of the monoclonal antibody originally produced by KM50. However, when this transfectant was injected intraperitoneally, it produced only a 9 mug ml(-1) concentration of granulocyte colony-stimulating factor in ascites, which is approximately 3 orders of magnitude less than the monoclonal antibody. This method may be applicable to production of other recombinant proteins, although further optimization in the conditions of production would be needed in order to reach much higher yields.

Lithiation of meso-octamethylcalix[4]pyrrole: a general route to C-Rim monosubstituted calix[4]pyrroles.

Lithiation and subsequent addition of an electrophile to meso-octamethylcalix[4]pyrrole provides a straightforward synthetic route to new, C-rim monosubstituted calix[4]pyrroles. A variety of electrophiles were used, resulting in calix[4]pyrroles with appended functional groups including carboxyl, ester, iodo, and formyl. This method was optimized to give maximum yields of the monosubstituted derivatives with lowest possible contamination by di- and trisubstituted congeners. Solid-state studies, performed for a number of these derivatives, showed unexpected supramolecular interactions involving both solvents and the monosubstituted calix[4]pyrrole derivatives themselves.

Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis.

BACKGROUND: Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication. However, the efficacy and the safety of this therapy in patients with liver cirrhosis have not been established. AIM: To evaluate the effect of hepatic dysfunction on metabolism of clarithromycin as it is used for H. pylori eradication therapy in patients with liver cirrhosis, and the efficacy of eradication therapy in those patients. METHODS: Serum levels of clarithromycin and its metabolite. 14-(R)-hydroxyclarithromycin, were examined in 18 subjects (five normal controls and 13 hospitalized patients with liver cirrhosis) on a selected day between days 7 and 10 of a 2-week course of eradication therapy. This therapy consisted of lansoprazole (30 mg, once a day) together with clarithromycin (200 mg, twice a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylori-positive out-patients, 88 with peptic ulcer and 30 with liver cirrhosis, underwent the same eradication therapy. RESULTS: Values for the area under the 0-6 h concentration-time curve (AUC) for clarithromycin were not significantly different among the groups. However, the AUC (0-6 h) values of 14-(R)-hydroxyclarithromycin were significantly lower in the Child-Pugh C group than in either the normal controls or the Child-Pugh A/B group. The cure rate for the peptic ulcer patients was 84% on a per protocol analysis (95% CI: 80%-88%) and 81% on an intention-to-treat analysis (95% CI: 77%-85%), while in the liver cirrhosis patients it was 89% in a per protocol analysis (95% CI: 78%-99%) and 83% in an intention-to-treat analysis (95% CI: 70%-97%). Mild adverse effects were observed in 10% of the peptic ulcer patients and 13% of the liver cirrhosis patients, with none leading to premature withdrawal from the study. CONCLUSION: The 2-week low-dose lansoprazole-based triple therapy tested is a simple, effective and well-tolerated regimen for H. pylori eradication in patients with liver cirrhosis.

Helicobacter pylori infection occurs via close contact with infected individuals in early childhood.

BACKGROUND: The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet, to date, the exact mode of transmission remains uncertain. METHODS: The seroprevalence of H. pylori in a relatively isolated rural town in Japan (A-town) was examined to analyse the H. pylori infection route. The immunoglobulin G antibodies against H. pylori in 1684 subjects who had received public health examinations in A-town were determined with an enzyme-linked immunosorbent assay. The seroprevalence was compared in five areas according to the water source. The possibility and frequency of intrafamilial infection was analysed by comparing the seroprevalence among family members residing in the same home. RESULTS: The seroprevalence of H. pylori did not differ significantly between the five areas examined. Seropositivity was significantly more common in the children whose mothers were seropositive (45.0%, 27/60) than in the children whose mothers were seronegative (10.0%, 2/20; odds ratio (OR) = 7.36, P = 0.0036, 95% confidence interval (CI) = 1.57-34.59). Seropositivity was significantly more common in the children whose older siblings were seropositive (55.0%, 22/40) than in the children whose older siblings were seronegative (23.5%, 20/85; OR = 3.97, P = 0.00051, 95% CI = 1.79-8.84). There was no significant relationship in seroprevalence between children and fathers, grandchildren and grandfathers, grandchildren and grandmothers, or within couples. Seropositivity was significantly more common in the adolescents who had attended a nursery school (44.4%, 20/45) than in the adolescents who had not attended a nursery school (25.6%, 109/426) (OR = 2.33, P = 0.0070, 95% CI = 1.24-4.36). CONCLUSIONS: The acquisition of H. pylori infection occurs by close contact with infected individuals in early childhood, especially via contact with infected mothers and other infected children.

Endoscopic [13C]-urea breath test for quantification of Helicobacter pylori infection.

BACKGROUND: We previously developed a new diagnostic method for Helicobacter pylori infection and called it the endoscopic [13C]-urea breath test (EUBT). Here we evaluate the relationship between the EUBT results and the histological findings. METHODS: The EUBT was performed on 137 patients with gastroduodenal diseases. After the collection of a baseline breath sample, gastroduodenal endoscopy was performed. Twenty milliliters of 0.05% phenol red solution containing 100 mg of [13C]-urea was sprayed over the entire gastric mucosa under endoscopic observation. A breath sample was collected 15 min after spraying. The content of 13CO2 in the breath samples was measured by ratio mass spectrometry. Two biopsy specimens each from the antrum and the middle corpus were obtained for culture and histology. Helicobacter pylori colonization, activity, inflammation, atrophy and intestinal metaplasia were classified on a four-point scale according to the Updated Sydney System. RESULTS: We found positive correlations between the EUBT values and the H. pylori colonization and activity score in the antrum and corpus, and negative correlations between the EUBT values and the atrophy and intestinal metaplasia scores in the corpus. CONCLUSIONS: The EUBT can be an indicator of the intragastric bacterial load and the histological findings for H. pylori.

Sequence analysis and clinical significance of the iceA gene from Helicobacter pylori strains in Japan.

The Helicobacter pylori iceA gene was recently identified as a genetic marker for the development of peptic ulcer in a Western population. To assess the significance of iceA subtypes of H. pylori in relation to peptic ulcer, 140 Japanese clinical isolates (88 from Fukui and 52 from Okinawa) were characterized. Sequence analysis of the iceA1 gene from 25 representative Japanese strains was also carried out to identify the differences in iceA between the ulcer group and the gastritis group. The iceA1 genotype was not correlated with the presence of peptic ulceration in either area. In addition, sequence analysis led to identification of five deletions and five point mutations (a nonsense mutation or a 1-bp insertion) within the iceA1 open reading frame corresponding to previously published sequences. These mutations were identified in both clinical groups (ulcer and gastritis groups) in each area. Local DNA sequence analysis revealed that the endpoints of all five deletions coincided with direct repeats. We also found four strains that carried longer iceA1 open reading frames compared with that for strain 60190. In conclusion, carriage of an iceA1 strain does not seem to be a risk factor for peptic ulcer in Japanese subjects. The critical mutations in the iceA1 gene in some isolates from patients with peptic ulcers suggested that IceA does not participate in the pathogenesis of peptic ulcer in Japan. We also found deletion hot spots that were associated with direct repeats in iceA1 and that favored a small-deletion model of slipped mispairing events during replication. We showed that iceA1 sequence variations may be useful tools for analysis of the population genetics of H. pylori.

The effect of helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia.

BACKGROUND: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non-ulcer dyspepsia. In addition, it has been reported that Helicobacter pylori induced inflammation of the gastric mucosa may affect gastric motility. AIM: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in non-ulcer dyspepsia patients. METHODS: A total of 46 non-ulcer dyspepsia patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori-positive non-ulcer dyspepsia patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after being cured of H. pylori infection. RESULTS: A total of 67.4% of the non-ulcer dyspepsia patients were H. pylori-positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in non-ulcer dyspepsia patients. H. pylori-positive non-ulcer dyspepsia patients were divided into three groups according to their gastric emptying: the delayed gastric emptying group, the normal gastric emptying group, and the rapid gastric emptying group. In the delayed and rapid gastric emptying groups, the gastric emptying and symptom scores were improved significantly by the eradication therapy. However, there was no improvement in symptom scores in the normal gastric emptying non-ulcer dyspepsia group by the eradication therapy. CONCLUSIONS: Disturbed gastric emptying and antral myoelectrical activity play roles in non-ulcer dyspepsia. Helicobacter pylori infection, inducing disturbed gastric emptying, may cause some non-ulcer dyspepsia symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in non-ulcer dyspepsia patients with disturbed gastric emptying. H. pylori eradication therapy is effective in H. pylori-positive non-ulcer dyspepsia patients with disturbed gastric emptying.

The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia.

BACKGROUND: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non-ulcer dyspepsia (NUD). Helicobacter pylori-induced inflammation of the gastric mucosa may affect gastric motility. AIM: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in NUD patients. METHODS: : Forty-six NUD patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori-positive NUD patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after cure of H. pylori infection. RESULTS: Sixty-seven per cent of NUD patients were H. pylori-positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in NUD patients. H. pylori-positive NUD patients were divided into three groups according to their gastric emptying: the delayed group, the normal group, and the rapid group. In the delayed and rapid gastric emptying groups, the emptying and symptom scores were improved significantly by eradication. There was no improvement in symptom scores in the normal gastric emptying NUD group by the eradication therapy. CONCLUSIONS: Disturbed gastric emptying and antral myoelectrical activity play roles in NUD. H. pylori-induced disturbed gastric emptying may cause some NUD symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in NUD patients with disturbed gastric emptying; H. pylori eradication therapy is effective in H. pylori-positive NUD patients with disturbed gastric emptying.

Bile reflux due to disturbed gastric movement is a cause of spontaneous gastric ulcer in W/Wv mice.

c-Kit is a receptor tyrosine kinase, and it is encoded by the mouse W locus. Mutant W/Wv mice develop spontaneous gastric antral ulcers. The aim of the present study was to investigate the pathogenesis of these gastric ulcers and to examine the effects of two antiulcer drugs; a proton pump inhibitor (2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H -benzimidazole sodium salt, rabeprazole) and a mucosal protective drug (geranylgeranylacetone, GGA), on the gastric ulcers. The inhibition of the gastric acid secretion by rabeprazole (30 mg/kg body weight, subcutaneous injection once a day for six weeks) significantly increased the gastric ulcer formation compared to the controls. In contrast, the GGA treatment (100 mg/kg body weight, oral administration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen in these mutant mice, and they showed no cyclic intense contractions in the gastric antrum. These results suggest that bile reflux due to the disturbance of gastric antral movement is a cause of the spontaneous gastric ulcers in W/Wv mice.