Biomedical subjects

F Sato

Publications and source records attributed to F Sato.

At least 145 records · Page 8Linked to original sources

PubMed1998

Make a difference: standardize your heel care practice.

The effective prevention and treatment of pressure ulcers has always been an essential nursing concern. Many advances, such as pressure reduction beds, have greatly reduced the incidence of ulcer development. In an urban teaching hospital the incidence of sacral ulcers decreased upon initiation of pressure reduction surfaces, while a concomitant increase in heel ulcers was noted. Heel ulcer prevention had not previously been singled out as a specific area of focus in skin pressure ulcer prevention. Given the increased incidence of occurrence of heel pressure ulcers in this institution's patient population, a multidisciplinary team met to address the issue of heel ulcer prevention. A quick, easy and user-friendly risk stratification tool was developed and guidelines for care of the at-risk patient were implemented. Initiation of the heel pressure ulcer identification tool and guidelines resulted in a decrease of heel pressure ulcer prevalence in the medical intensive care unit patient population.

Clinical Nursing Research↗

PubMed1998

Detection of coccoid Helicobacter pylori: light microscopical immunogold silver enhancing stain.

BACKGROUND: Helicobacter pylori (H. pylori) can be morphologically divided into spiral and coccoid forms. Although many different staining procedures for light microscopy have been developed to detect H. pylori, there are no reports that the coccoid forms can be specially identified by a staining method. The ability to identify the coccoid form of H. pylori by light microscopy would be important for studies evaluating its possible role in gastric disease. We examined whether both the coccoid and the spiral forms could be stained using anti-H. pylori antibody. METHODS: Specimens from the stomachs of dyspeptic patients with proven H. pylori infection and H. pylori from culture (1st and 4th day) were stained with the light microscopic immunogold silver enhancing stain using the rabbit IgG specific for H. pylori. Cultured H. pylori was also stained with electron microscopic immunogold staining method using the same antibody. The number of coccoid forms was counted by scanning electron microscopy. RESULTS: Biopsies and H. pylori from 6 patients were studied. H. pylori from both biopsy material and culture appeared as black organisms by light microscopic immunogold silver enhancing stain. The coccoid forms constituted 0.4% and 98.3% on days 1 and 4 of culture, respectively (by scanning electron microscopy). The antigen recognized by the anti-H. pylori antibody was located on the surface of the flagella, the cell wall, or in the cytoplasm by immunoelectron microscopy. CONCLUSION: This study shows that both spiral and coccoid forms of H. pylori can be detected by light microscopic immunogold silver enhancing stain using anti-H. pylori antibody. This simple stain is to be proven useful for studies aimed at understanding whether the coccoid form plays a role in disease.

Animals↗

PubMed1998

Effects of rebamipide in combination with lansoprazole and amoxicillin on Helicobacter pylori-infected gastric ulcer patients.

The aim of this study was to compare the additive effect of rebamipide with that of teprenone in combination with dual therapy on H. pylori eradication. A total of 102 H. pylori-positive gastric ulcer patients were assigned at random to two groups; in addition to dual therapy (amoxicillin 500 mg thrice daily and lansoprazole 30 mg every morning for two weeks), one group received rebamipide 100 mg thrice daily for eight weeks, while the other group received teprenone 50 mg thrice daily for eight weeks. H. pylori diagnosis after treatment was made by [13C]UBT. The ulcer healing rate was 85.7% in the rebamipide group and 79.5% in the teprenone group (P = NS). The eradication rate was 68.4% (95% CI = 54-83%) in the rebamipide group and 47.7% (95% CI = 32-61%) in the teprenone group (P = 0.043) by per-protocol analysis. These findings suggest that the efficacy of dual therapy may be increased by the administration of rebamipide.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

Growth and maturation of small hepatocytes.

Proliferation of adult rat hepatocytes is observed in serum-free Dulbecco's modified Eagle's medium (DMEM) supplemented with 10 mmol/L nicotinamide and 10 ng/mL epidermal growth factor (EGF). The proliferating cells are mainly mononucleate and form small cell colonies surrounded by mature hepatocytes. Although these cells in focal colonies have a less-differentiated appearance, immunocytochemically and ultrastructurally they possess hepatic characteristics. The size of small hepatocytes is one-third to half that of mature hepatocytes. Therefore, we call the cells forming a colony, small hepatocytes. The small hepatocytes can be subcultured for several passages. Furthermore, the cells are rich in the supernatant following 50 g centrifugation for 1 min after collagenase liver perfusion. When the cells are cultured in DMEM supplemented with 10% foetal bovine serum, 10 mmol/L nicotinamide, 1 mmol/L ascorbic acid 2-phosphate, 10 ng/mL EGF and 1% dimethyl sulphoxide, each small hepatocyte can clonally proliferate for more than 3 months. A small hepatocyte divides to form a colony and the number of cells reaches more than 100 within 20 days. With time in culture, cells with a large cytoplasm appear within a colony. They have many mitochondria and large peroxisomes with crystalline nucleoids and are typical, mature hepatocytes. Immunoreactivity to connexin 32 and well-developed bile canaliculus structures are often observed in the cell-cell borders. Thus, we suggest that small hepatocytes may be considered to be 'committed progenitor cells' that can further differentiate into mature hepatocytes.

Animals↗

PubMed1998

Ten minute 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

We investigated the utility of a 10-min 13C-urea breath test (13C-UBT) using 100mg of 13C-urea; this is a simple and rapid method for the detection of Helicobacter pylori infection. One hundred and fifty-one patients in whom the identification of H. pylori was established by rapid urease test, culture, and histology of six biopsy specimens underwent 254 13C-UBT examinations before and/or after eradication treatment. In the 133 patients who did not receive eradication treatment, the calculated sensitivity of the 10-min 13C-UBT was 99.4% and specificity 100% when the cut-off point was set at 3.5/1000, using a mass spectrometer. In the 121 patients who received eradication treatment, this cut-off point gave a sensitivity of 86.7%, a specificity of 99.1%, and a positive predictive value of 92.9%, with a negative predictive value of 98.1%. There were no significant differences between the diagnosis of H. pylori infection at 1 month and more than 3 months after the endpoint of eradication treatment. The 10-min 13C-UBT is suitable for the diagnosis of H. pylori infection before and after eradication treatment.

Breath Tests↗

PubMed1997

Serial electron microscopic reconstruction of axon terminals on physiologically identified thalamocortical neurons in the cat ventral lateral nucleus.

The distribution of different types of terminals on different portions of single thalamocortical neurons (TCNs) was quantitatively investigated in the cat ventral lateral nucleus (VL) by the application of computer-assisted three-dimensional reconstruction from serial ultrathin sections. Single neurons in the VL were intracellularly penetrated with a glass micropipette filled with horseradish peroxidase (HRP), and were electrophysiologically identified as TCNs by their antidromic responses to stimulation of the motor cortex. These TCNs received monosynaptic excitation from the contralateral cerebellum. After electrophysiological identification, they were injected with HRP iontophoretically. The spatial distribution of terminals of different types on two identified TCNs was analyzed on serial ultrathin sections, some of which were stained by a postembedding immunogold technique by using a gamma-aminobutyric acid (GABA) antibody. Terminals that synapsed on the injected cells were categorized as LR terminals (GABA-negative large axon terminals containing round vesicles), SR terminals (GABA-negative small axon terminals containing round vesicles), P terminals (GABA-positive axon terminals of various sizes containing pleomorphic vesicles), or PSDs (presynaptic dendrites). The order of dendritic branches of labeled TCNs was determined by computer-assisted reconstruction from serial sections. LR terminals made contacts mainly with proximal dendrites of TCNs. SR terminals made contacts predominantly with distal dendrites, and were never found on somata or primary dendrites. P terminals were observed on somata and on every portion of the dendritic trees. Synapses formed by PSDs were concentrated on the proximal dendrites and sometimes formed synaptic triads with LR terminals. Only a few terminals were found on somata, all of which were P type. Therefore, terminals belonging to different classes were not uniformly distributed on the somata and dendrites of single TCNs. These results suggest that terminals originating from different sources may preferentially contact specific regions of TCNs in the VL, and their topographical locations reflect the electrophysiological response properties of the TCNs.

Animals↗

PubMed1997

Heart rate during obstructive sleep apnea depends on individual hypoxic chemosensitivity of the carotid body.

BACKGROUND: In patients with obstructive sleep apnea syndrome (OSAS), there are cyclic fluctuations in heart rate (HR), that is, bradycardia during apnea followed by abrupt tachycardia on resumption of ventilation. Although a previous study suggested that the degree of bradycardia observed during central apnea at high altitude was determined by individual hypoxic chemosensitivity of the carotid body, it is not known whether this is true for subjects with obstructive sleep apnea syndrome. METHODS AND RESULTS: First, we examined apnea-associated HR changes in II subjects with OSAS and analyzed the relationship of the HR change during apnea (delta HR, defined as the difference between the values at the beginning and the end of apnea) and apnea-induced nadir SaO2 in each subject. Second, we conducted an apnea-simulation study in 7 subjects to examine whether the individual pattern of delta HR could be simulated while they held their breath under different levels of arterial oxygenation. The delta HR was highly variable among subjects: 2 showed an increase in HR during apnea, 6 a decrease, and the other 3 a borderline-type response. The slope factor of the nadir of the SaO2-delta HR line obtained from each subject had a significant correlation with the HR change during breath-holding conducted under normoxia (Spearman's rank correlation coefficient, rs = 69, P < .05) or hypoxia (rs = .81, P < .05) but not under hyperoxia. Finally, we evaluated hypoxic chemosensitivity of the carotid body by measuring the ventilatory response to isocapnic progressive hypoxia in all subjects. The magnitude of the ventilatory response ranged from 0.05 to 1.89 L.min-1.%SaO2 fall-1 and showed a significant correlation with the slope factor of the nadir of the SaO2-delta HR line (rs = -.64, P < .05). CONCLUSIONS: The intersubject variation of the HR changes during sleep apnea can be explained in large part by individual hypoxic chemosensitivity of the carotid body regardless of the type of apnea.

Adult↗

PubMed1997

Competence of a migratory bird, red-bellied thrush (Turdus chrysolaus), as an avian reservoir for the Lyme disease spirochetes in Japan.

To evaluate the competence of migratory birds as reservoirs for the Lyme disease spirochetes, we examined two species of migrants, Red-bellied thrush (Turdus chrysolaus) and Black-faced bunting (Emberiza spodocephala) in Nemuro, the northern part of Japan. Spirochetes were found in four individual birds out of 11 T. chrysolaus, three isolates were detected from the skins and the other one was obtained from the liver. No spirochete was found to be infected in 20 E. spodocephala. As far as we know, this is the first record of direct detection of the spirochetes from migratory birds in Japan. The spirochetes were also isolated from immature ixodid ticks, Ixodes persulcatus, fed on those species of birds. The spirochetes were transmitted trans stadially to the next stage, when infected ticks molted. All of the isolates from birds and ticks were identified as Borrelia garinii by our ribotyping and flagellin gene sequence analyses. Our results strongly suggest that the migratory birds are reservoirs in the transmission of the Lyme disease spirochetes in Japan.

Animals↗

PubMed1997

Advanced glycation end products-driven angiogenesis in vitro. Induction of the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor.

This study was undertaken to determine whether and how advanced glycation end products (AGE), senescent macroproteins accumulated in various tissues under hyperglycemic states, cause angiogenesis, the principal vascular derangement in diabetic microangiopathy. We first prepared AGE-bovine serum albumin (BSA) and anti-AGE antiserum using AGE-RNase A. Then AGE-BSA was administered to human skin microvascular endothelial cells in culture, and their growth was examined. The AGE-BSA, but not nonglycated BSA, was found to induce a statistically significant increase in the number of viable endothelial cells as well as their synthesis of DNA. The increase in DNA synthesis by AGE-BSA was abolished by anti-AGE antibodies. AGE-BSA also stimulated the tube formation of endothelial cells on Matrigel. We obtained the following evidence that it is vascular endothelial growth factor (VEGF) that mainly mediates the angiogenic activities of AGE. (1) Quantitative reverse transcription-polymerase chain reaction analysis of poly(A)+ RNA from microvascular endothelial cells revealed that AGE-BSA up-regulated the levels of mRNAs for the secretory forms of VEGF in time- and dose-dependent manners, while endothelial cell expression of the genes encoding the two VEGF receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase 1, remained unchanged by the AGE treatment. Immunoprecipitation analysis revealed that AGE-BSA did increase de novo synthesis of VEGF. (2) Monoclonal antibody against human VEGF completely neutralized both the AGE-induced DNA synthesis and tube formation of the endothelial cells. The results suggest that AGE can elicit angiogenesis through the induction of autocrine vascular VEGF, thereby playing an active part in the development and progression of diabetic microangiopathies.

Cell Division↗

PubMed1997

EM574, an erythromycin derivative, is a motilin receptor agonist in the rabbit.

This study was performed to examine whether an erythromycin derivative, de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) is a motilin receptor agonist in the rabbit gastrointestinal tract. EM574 and porcine motilin induced contractions in segments of isolated rabbit intestine with pEC50 values of 8.26 +/- 0.04 and 8.69 +/- 0.07, respectively, but not in rat or guinea pig preparations. The sensitivity and efficacy of the response to both compounds in rabbits decreased aborally and was insensitive to pretreatment with atropine or tetrodotoxin, but was markedly suppressed under Ca(2+)-free conditions. EM574 and porcine motilin specifically displaced [125I-Tyr23]canine motilin bound to gastric antral smooth muscle homogenates with plC50 values of 8.21 +/- 0.13 and 9.20 +/- 0.11, respectively. The pEC50 value for the contractile response and plC50 value for the receptor binding for motilin, EM574, erythromycin A and three other derivatives correlated well (r = 0.94, P < 0.01). Tissue section autoradiography in the antrum revealed that specific labeled motilin binding sites were localized in the circular muscle layer and myenteric plexus, and could be reduced in the presence of an excess of EM574. These results indicate that EM574 is a potent motilin receptor agonist in the rabbit gastrointestinal tract.

Animals↗

PubMed1997

Comparison of the nucleotide sequence of enteroaggregative Escherichia coli heat-stable enterotoxin 1 genes among diarrhea-associated Escherichia coli.

The presence of the enteroaggregative Escherichia coli (EAggEC) heat-stable enterotoxin 1 (EAST1) gene was investigated in 15 strains each of EAggEC, enteropathogenic E. coli (EPEC), EPEC-related strains of non-EPEC serotypes, diffusely adhering E. coli (type 1 DAEC) that carries F1845 adhesive pili (or a related adhesin), and enteroinvasive E. coli (EIEC) by PCR and colony hybridization. The EAST1 gene or its homologue was present in 53.3% of EAggEC, 20% of EPEC, 13.3% of the EPEC-related strains, and 6.7% of type 1 DAEC, EIEC and E. coli unrelated with diarrhea had no gene with sequence similarity to the EAST1 gene. Comparison of the EAST1 gene sequences analyzed in this study as well as those reported previously showed that EAggEC (including strain O42, which was shown to be pathogenic in volunteer experiments), EPEC, type 1 DAEC, type 2 DAEC (which carries the 57-kDa outer membrane protein as an adhesin), and enterotoxigenic E. coli shared a common sequence. A variant type of the EAST1 gene sequence was present in the EAggEC strain 17-2 (initially characterized for the EAST1 gene) and in an EPEC-related strain of a non-EPEC serotype. These data suggest that the EAST1 gene or its variant is a virulence gene widely distributed among diarrhea-associated E. coli.

Amino Acid Sequence↗

PubMed1997

Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

Adult↗

PubMed1997

Susceptibility of Helicobacter pylori isolates to metronidazole, clarithromycin and amoxycillin in vitro and in clinical treatment in Japan.

BACKGROUND: Primary and acquired resistance to antibiotics is an important factor in determining the reason for treatment failure in Helicobacter pylori infection. We examined the relationship between the susceptibility of H. pylori isolates and the efficacy of chemotherapy. METHODS: The minimal inhibitory concentrations (MICs) of metronidazole (MNZ), clarithromycin (CLAR) and amoxycillin (AMOX) of 320 H. pylori pre-treatment isolates were determined by the agar dilution method. In 290 patients with peptic ulcers. H. pylori infection was treated by dual or triple combination therapies for 2 weeks: one proton pump inhibitor (30 mg/day lansoprazole or 20 mg/day omeprazole) and one or two antibiotics (500 mg AMOX, 200 mg CLAR or 250 mg MNZ twice a day). MICs were also determined after the treatment failure. RESULTS: Among the drugs tested, for MNZ and CLAR, 8.1% and 9.1% of the isolates, respectively, were resistant, while no isolate was resistant to AMOX. After unsuccessful treatment using MNZ and CLAR, 66.7% and 70.61% of the isolates changed from sensitive to resistant, respectively. All isolates were sensitive to AMOX after treatment failure. CONCLUSIONS: The failure of the H. pylori treatment results in the induction of resistance to CLAR and/or MNZ. Regimens with a high cure rate should be used in order to prevent the generation of acquired resistance to antibiotics.

Adolescent↗

PubMed1997

Purification and characterization of tobacco pathogenesis-related protein PR-5d, an antifungal thaumatin-like protein.

Cultured tobacco cells accumulate several pathogenesis-related proteins. A neutral PR-5 protein, PR-5d, was purified to homogeneity from such cells. PR-5d has highly hydrophobic characteristics, but hydropathy analysis of its primary structure did not show a hydrophobic domain. In a series of bioassays, purified PR-5d showed inhibitory activity against several phytopathogenic and non-phytopathogenic fungi as do other members of the PR-5 protein family. To study the antifungal mechanism based on three dimensional structure of PR-5d, purified PR-5d was crystallized. The preliminary X-ray analysis of the crystal revealed that the crystals belong to space group C2, with cell dimensions a = 80.2 A, b = 63.8 A, c = 45.7 A, and beta = 107.2 degrees, and diffract at least 1.8 A resolution.

Amino Acid Sequence↗

PubMed1997

A novel protein with DNA binding activity from tobacco chloroplast nucleoids.

A 41-kD DNA binding protein with a basic pl was purified from chloroplast nucleoids in photomixotrophically cultured tobacco cells, and its amino acid sequence was determined. Using this sequence information, its cDNA (CND41) was isolated, and its nucleotide sequence was determined. The predicted amino acid sequence of CND41 has a transit peptide of 120 amino acids and a mature protein of 382 amino acids. A distinctive helix-turn-helix motif in the lysine-rich N-terminal region of the mature protein and an aspartyl protease active site motif were predicted. Expression of a series of truncated CND41 proteins in Escherichia coli indicated that the lysine-rich region is essential for DNA binding and that CND41 nonspecifically binds chloroplast DNA. Protein gel blot analyses showed CND41 mainly in cells and/or tissues containing nonphotosynthesizing, actively growing plastids. In addition, the accumulation of chloroplast transcripts in these cells and/or tissues (e.g., transcripts for QB binding protein of photosystem II [psbA] and large subunit of ribulose bisphosphate carboxylase [rbcL]) was negatively correlated with the accumulation of CND41. Analyses of cultured cells of transgenic tobacco with reduced CND41 levels showed a higher level of expression of chloroplast genes compared with that of the wild type. We discuss the possible function of CND41 as a negative regulator of chloroplast gene expression.

Amino Acid Sequence↗

PubMed1997

Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan.

Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.

Antigens, Bacterial↗

PubMed1997

Effects of Helicobacter pylori eradication therapy on hyperammonaemia in patients with liver cirrhosis.

BACKGROUND AND AIMS: Helicobacter pylori has strong urease activity. Ammonia produced by H pylori in the stomach can be a source of systemic ammonia in patients with hepatic dysfunction. The effect of the eradication of H pylori on hyperammonaemia was examined in patients with liver cirrhosis. SUBJECTS AND METHODS: Ammonia concentrations in blood and gastric juice were analysed in 50 patients with liver cirrhosis and hyperammonaemia. All patients were first treated with a low protein diet, kanamycin, lactulose, and branched chain enriched amino acid solution. Hyperammonaemia remained in 18 patients. These 18 patients were divided into three groups according to the status of H pylori infection; those with a diffuse distribution of H pylori in the stomach (group I), those with a regional distribution (group II), and those without H pylori (group III). These patients were given 30 mg iansoprazole, 1000 mg amoxicillin, and 400 mg clarithromycin or 500 mg metronidazole for two weeks to eradicate H pylori. RESULTS: In group I ammonia concentrations in blood and gastric juice were significantly reduced after H pylori eradication. The blood ammonia concentration at 12 weeks after the eradication was still significantly lower than that before eradication. In groups II and III the ammonia concentrations in blood and gastric juice were not significantly reduced after eradication therapy. CONCLUSIONS: The diffuse distribution of H-pylori in the stomach contributes partly to hyperammonaemia in patients with liver cirrhosis, and the eradication of H pylori is effective in patients with hyperammonaemia with diffuse H pylori infection in the stomach.

Adult↗

PubMed1997

Prevention of gastric ulcer relapse induced by indomethacin in rats by a mutein of basic fibroblast growth factor.

We found indomethacin aggravates healed gastric ulcers (ulcer relapse) in rats. In the present study, we examined the effects of human basic fibroblast growth factor (bFGF) mutein CS23 (TGP-580) and histamine H2-receptor antagonists (H2-RAs) on ulcer relapse in this model. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Indomethacin (1 mg/kg/day) given s.c. for 2 weeks starting 4 weeks after the operation aggravated the healed ulcer; the areas with and without indomethacin were 4.8 +/- 1.4 and 0.4 +/- 0.3 mm2, respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administration period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/kg) and TGP-580 (0.1 mg/kg) for 4 weeks accelerated the healing. The aggravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. When the drugs were co-administered with indomethacin for 2 weeks, the aggravation was significantly prevented by ranitidine and mildly inhibited by cimetidine and TGP-580. Both TGP-580 and H2-RAs can prevent the ulcer relapse induced by indomethacin but via different modes of action: TGP-580 inhibits relapse mainly by acting on the process of healing, while H2-RAs act mainly on the process of aggravation.

Acetic Acid↗