Biomedical subjects

K Kihira

Publications and source records attributed to K Kihira.

At least 55 records · Page 3Linked to original sources

PubMed1995

Dual therapy with lansoprazole and clarithromycin for eradication of Helicobacter pylori.

AIM: To evaluate the eradication of Helicobacter pylori by therapy with a combination of 60 mg lansoprazole and 800 mg clarithromycin. PATIENTS AND METHODS: In an open therapeutic trial, 30 H. pylori-positive patients with active ulcer disease took 30 mg lansoprazole twice a day and 400 mg clarithromycin twice a day for the first 2 weeks, followed by 30 mg lansoprazole once a day for 4-6 weeks. Endoscopy was performed both before and at the end of therapy, and 4 weeks after the end of the therapy. H. pylori was detected by using a combination of smear, culture and tissue sections. RESULTS: Complete pain relief occurred within 3 days in all patients and all ulcers were healed by the end of the therapy. The H. pylori clearance rate was 83.3% and the eradication rate was 73.3%. A minor side effect (metallic taste) was reported by only one patient (3.3%). CONCLUSIONS: Therapy with a combination of 60 mg lansoprazole and 800 mg clarithromycin is efficacious in the eradication of H. pylori and has the advantage of a low incidence of side effects and quick pain relief for patients with active ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Helicobacter pylori detected deep in gastric glands: an ultrastructural quantitative study.

To determine the presence of Helicobacter pylori deep in the gastric glands and in the parietal cell canaliculi, biopsied specimens from 15 patients were observed by electron microscopy. In the specimens, 818 H. pylori and 1,846 parietal cells were detected. Most of the H. pylori (93.9%, 768/818) were present on the mucosal surface. However, a few organisms (50/818, 6.1%) were detected deep in the mucosa. The mean number of H. pylori per specimen was 2.13 (32/818, 3.9%) and 1.20 (18/818, 2.2%), deep in the gland and in the parietal cell canaliculi, respectively. All appeared morphologically intact. Although the combination of culture and histology from biopsy tissues is usually used for isolation of H. pylori in most laboratories, such organisms are considered difficult to detect with conventional methods and to dislodge with antimicrobial therapy. Therefore, H. pylori present deep in the mucosa are suggested to be one of the factors in recrudescence after eradication therapy. In addition, H. pylori in the parietal cell canaliculi may affect parietal cell function or alter gastric physiology.

Adult↗

PubMed1994

Comparative studies of metabolism of simultaneously administered chenodeoxycholic acid and ursodeoxycholic acid in hamsters.

We present the comparative studies of metabolism of chenodeoxycholic acid and ursodeoxycholic acid and their taurine conjugates in the liver and fecal culture from hamsters. When [24-14C]chenodeoxycholic acid and [11,12-3H]ursodeoxycholic acid were simultaneously instilled into the jujunal loop of bile fistula hamsters, both bile acids administered were recovered mainly as their conjugates with taurine and glycine in the fistula bile. The recovery of chenodeoxycholic acid was slightly but significantly higher than that of ursodeoxycholic acid. Chenodeoxycholic acid was more efficiently conjugated with glycine than ursodeoxycholic acid. The glycine/taurine ratio in the biliary chenodeoxycholic acid was 1.9, and that in ursodeoxycholic acid was 1.6. In addition, as much as 6.2% of ursodeoxycholic acid was excreted as the unconjugated form; on the other hand only 2.4% of unconjugated chenodeoxycholic acid was excreted. When [24-14C]chenodeoxycholyltaurine and [11,12-3H]ursodeoxycholyltaurine were simultaneously administered into the ileum loop of bile fistula hamsters, both bile salts were absorbed and secreted efficiently into the bile at the same rate. These results indicate that slightly lower recovery of ursodeoxycholic acid in the bile could be due to the less effective conjugation of ursodeoxycholic acid than chenodeoxycholic acid in the liver. Deconjugation by fecal culture from a hamster proceeded more rapidly in chenodeoxycholyltaurine than ursodeoxycholyltaurine. 7-Dehyroxylation to form lithocholic acid by fecal culture was also faster in chenodeoxycholic acid than ursodeoxycholic acid. The formation of 7-oxolithocholic acid from ursodeoxycholic acid was lesser than from chenodeoxycholic acid. In summary, bacterial deconjugation followed by 7-dehydroxylation to form lithocholic acid seems to be achieved more efficiently with chenodeoxycholic acid than ursodeoxycholic acid.

Animals↗

PubMed1994

Determination of the glucurono-conjugated position in bile alcohol glucuronides excreted in urine of a patient with cerebrotendinous xanthomatosis by a nuclear magnetic resonance study.

This paper describes the determination of the glucurono-conjugated position in two bile alcohol glucuronides excreted in urine of a patient with cerebrotendinous xanthomatosis by a nuclear magnetic resonance study. The urine sample was extracted with reversed-phase resin, and chromatographed on a reversed-phase partition column and a silica gel column to isolate glucurono-conjugates of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23,25- pentol. Proton and carbon-13 nuclear magnetic resonance spectra of the natural tetrol glucuronide were identical with those of the chemically synthesized tetrol glucuronide, 7 alpha, 12 alpha, 25-trihydroxy-5 beta-cholestane-3 alpha-O-beta-D- glucopyranosyluronic acid. Hence, the glucurono-conjugated position of the natural tetrol glucuronide was determined to be the C-3 position. By comparison of the 13C chemical shift data with that of the unconjugated pentol, 5 beta-cholestane-3 alpha, 7 alpha, 23,25-pentol, the glucurono-conjugated position of the natural pentol glucuronide was determined to be C-23. Thus the natural pentol glucuronide can be formulated as 3 alpha, 7 alpha, 12 alpha, 25- tetrahydroxy-5 beta-cholestane-23-O-beta-D-glucopyranosyluronic acid. The difference in the glucurono-conjugated position between the 25-tetrol glucuronide and the 23,25-pentol glucuronide indicates that the former is not the biosynthetic precursor of the latter.

Cholestanols↗

PubMed1994

Changes of cholecystokinin octapeptide tissue levels in rat brain following dopamine neuron lesions induced by 6-hydroxydopamine.

Cholecystokinin octapeptide sulfated (CCK8) tissue levels in several regions of the rat brain were measured by amino terminal specific radioimmunoassay following the intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) to investigate the interaction between CCK8 and dopamine (DA). Pargyline and desmethylimipramine were administered 2 h before 6-OHDA injection. The levels of CCK8-like immunoreactivity in the frontal cortex, striatum, hippocampus, substantia nigra, and nucleus accumbens increased transiently on day 1 after 6-OHDA treatment. The levels in the frontal cortex, striatum and substantia nigra fell gradually to reach a subnormal level on day 7. In the nucleus accumbens, where the coexisting CCK8 and DA neurons lie, the tissue levels fell to a subnormal level on day 3. These decreased levels were unchanged until day 28. The irreversible destruction of DA neurons induced by 6-OHDA might cause drastic changes in regional CCK8-like immunoreactivity. The changes would depend on the neuromorphological differences in each structure. These results suggest that the CCK8 systems are closely related to the DA systems in several brain regions and that DA plays an important role in CCK8 release.

Animals↗

PubMed1994

Morphological aspects of the cytotoxic action of Helicobacter pylori.

OBJECTIVE: To morphologically investigate the cytotoxic action of Helicobacter pylori on gastric mucosal cells. METHODS: Twenty biopsy specimens were obtained from the antrum and greater curvature of the upper body of the stomach, and examined by electron microscopy to elucidate the process of mucus cell injury induced by H. pylori. RESULTS: Only H. pylori colonies in intimate contact with the mucosal cells caused various cell alterations, including loss of microvilli, mucus depletion, cell membrane injury and degeneration of the cytoplasm. In contrast, H. pylori that were not in contact with the mucosa had no effect on the surface mucus cells. CONCLUSIONS: The results of this study suggested the following mechanism of H. pylori-induced gastric mucosal injury. Intimate contact between H. pylori and the epithelial cell is necessary for cytotoxic action. During the process of cytotoxic action, degradation of the mucous gel layer and the glycocalyx are first caused by the proteolytic enzymes produced by H. pylori. Then the microorganism approaches the surface mucus cell, making intimate contact with the cell surface. Finally, H. pylori adheres directly to the cell membrane, effecting direct action of the toxins on the cell membrane. Subsequently, the degenerative changes induced destroy the cell membrane, resulting in degeneration of the cell itself.

Bacterial Adhesion↗

PubMed1994

Relationship between Helicobacter pylori and atrophic gastritis.

OBJECTIVES: To investigate the relationship between Helicobacter pylori and atrophic gastritis. DESIGN AND METHODS: The extent of atrophic gastritis was assessed endoscopically in 97 non-ulcer patients, and their H. pylori status was assessed by enzyme-linked immunosorbent assay. RESULTS: The prevalence of H. pylori infection was greatest in the early stages of atrophic gastritis. Small numbers of H. pylori-negative patients were identified at different stages during the extension of atrophic gastritis. CONCLUSIONS: H. pylori infection precedes the extension of atrophic gastritis, and a minority of patients with atrophic gastritis may never have been infected with H. pylori.

Adolescent↗

PubMed1994

Bile salts of the toad, Bufo marinus: characterization of a new unsaturated higher bile acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid.

The bile salts present in gallbladder bile of the toad, Bufo marinus, were found to consist of a mixture of bile alcohol sulfates and unconjugated bile acids. The major bile alcohol was 5 beta-bufol; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha, 26-tetrols occurred as the minor bile alcohols. Bile acids of Bufo marinus were cholic acid, allocholic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha- and 5 beta-cholestan-26-oic acids, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha- and 5 beta-cholest-23-en-26-oic acids, 3 alpha,7 alpha,12 alpha, 26-tetrahydroxy-5 beta-cholestan-27-oic acid, and a C27 bile acid which has not been previously described. By chromatographic behavior, mass spectral data, and identification of the products of catalytic hydrogenation and ozonolysis, the structure of the new higher bile acid was elucidated as 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid. The bile salt pattern of Bufo marinus closely resembles that of Bufo vulgaris formosus, except for the absence of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-22-ene-24-carboxylic acid, the major bile acid of the latter toad.

Animals↗

PubMed1994

Pharmacokinetic behavior of cyclosporine A in liver dysfunction.

The pharmacokinetic behavior of cyclosporine A (CyA), known as a potential immunosuppressive agent to prevent graft rejection in transplantation, was studied in patients with acute hepatitis and primary biliary cirrhosis (PBC). The ratios of blood concentration of total CyA (CyA and its metabolites), CyA, and CyA metabolites to dose/kg body weight, (t-CyA/dose, CyA/dose, and CyA-Met/dose, respectively) were significantly higher in patients with hepatitis than those in renal transplantation. In PBC patients these ratios showed a tendency to be smaller than those in renal transplantation, but were not significant. The ratio of CyA-Met/CyA was higher in the patients with hepatitis and PBC than that in renal transplantation. It was highest in the patients with PBC. The ratio of CyA-Met/CyA was significantly increased with a decrease of liver functions evaluated by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total serum bilirubin (t-Bil). These results indicate that hepatic function affects the pharmacokinetic behavior of CyA and the increased ratio of CyA-Met/dose could be caused by a possible increased efflux of metabolites into the blood circulation due to impaired bile excretion. These results also indicate the importance of therapeutic drug monitoring (TDM) in the use of CyA with patients with hepatic dysfunction.

Acute Disease↗

PubMed1994

Some personal comments on the Sydney system for the classification of chronic gastritis.

The Sydney system for the classification of chronic gastritis is a system for describing the histopathological findings of a biopsy specimen. It involves the analysis of two to four biopsies of the gastric mucosa taken from arbitrary sites, which, taken alone, are insufficient for extrapolation to the diagnosis of the whole stomach. The system seems to be useful as a computer-oriented method fo documenting the histopathological analysis of the two to four biopsy specimens obtained from the arbitrary sites in the antrum or corpus. One biopsy specimen is obtained from the anterior wall of the antrum, the other from the posterior wall. They would be better obtained from the lesser and greater curvatures, which areas would provide more accurate data concerning the antrum or body. While this may be invaluable for researchers with particular interests, it is quite valueless for the majority of clinicians who must diagnose and treat their patients. When a classification is made, its purposes should, firstly, be clear and definite. Secondly, the classification should be simple and easy to use. If a classification is effective, it will be widely used. However, in this field, it is almost impossible to achieve a classification that will fully satisfy all practitioners and researchers with different interests. The Sydney system alone is not sufficient for the classification of chronic gastritis. It is merely a system for describing the histopathological findings of biopsy specimens. It does not allow for an integrated diagnosis of chronic gastritis of the entire stomach.

Adolescent↗

PubMed1993

Endoscopic ultrasonographic (EUS) evaluation of the quality of gastric ulcer healing.

EUS provides cardinal tomographic findings of gastric ulcer such as low echo mass (ulcer echo), thickening of the wall, a symmetrical or asymmetrical convergence of the submucosal layer, and a sharp (pin-point) or blunt (broad-surface) convergence, variously expressed in accordance with the depth or width, and also with the history of recurrence of ulcer. A low echo mass, or an ulcer echo histopathologically consists of fibrosis and granulation, sonographically correlating well with the thickening of the wall. Seventy nine cases of ulcer scar, 52 of which were evaluated endoscopically as S1 (red scar) and 27 as S2 (white scar), were scanned by EUS. The incidence of high quality healing recognized on EUS with complete disappearance of a low echo mass and subsidence of the wall thickness was 21.2% (11 of 52 ulcer scars) in the S1 stage group, which remarkably increased up to 70.4% (19 of 27) in the S2 group (P < 0.01). The results indicate a definite correlation between endoscopic and EUS assessment of an ulcer scar state. The cumulative relapse rate at 12 months during maintenance therapy with half doses of H2 blocker was found to be 4.5% (1 of 22 cases) in the group with high quality healing on EUS, 40.9% (9 of 22) in the group with fair quality healing, and 75.0% (12 of 16) in the group with poor quality healing. The results of the present study suggest that EUS assessment may be a reliable and objective predictor of susceptibility to ulcer recurrence, accurately evaluating the quality of gastric ulcer healing.

Gastroscopy↗

PubMed1993

Age-related changes in the microvessels of the human stomach: an ultrastructural study.

The ultrastructure of microvessels in the gastric mucosa of patients with atrophic gastritis was investigated. In the gastric mucosa of atrophic gastritis, the endothelial cells of microvessels were irregularly swollen and subendothelial spaces were enlarged. The basement membrane underlying the endothelium was thickened. Degeneration of smooth-muscle cells was also evident in the media. These changes appear to correspond to sclerosis or aging of the microvessels. Such sclerotic changes in microvessels may initiate deterioration of the microenvironment in the gastric mucosa and may consequently affect metabolic activity of the gastric mucosal cells. Those sequences might induce degeneration or abnormal differentiation of mucosal cells. Such vascular changes may advance slowly and increase in intensity with advancing age. The final result would be the histologic changes associated with atrophic gastritis.

Aged↗

PubMed1993

Enzymatic formation of D-cysteinolic acid conjugated chenodeoxycholic acid in liver preparation from red seabream, Pagrosomus major.

The enzymatic formation of D-cysteinolic acid conjugated chenodeoxycholic acid in liver preparation from a marine teleost, wild and cultured red seabream, Pagrosomus major, was investigated. [24-14C]Chenodeoxycholic acid was incubated with taurine, glycine, or D-cysteinolic acid in the liver preparation in the presence of CoA, ATP, NAD+ and FAD. D-Cysteinolic acid could be conjugated efficiently with chenodeoxycholic acid to give chenodeoxycholyl-D-cysteinolic acid in both wild and cultured red seabream liver preparations, though the production rate was slower than that of the formation of chenodeoxycholyltaurine. Under the conditions employed, glycine was not utilized as the substrate for the conjugation at all. The formation of chenodeoxycholyl-D-cystenolic acid was decreased by the addition of various concentrations of taurine to the incubation mixture. These results suggest that bile acid-CoA: amino acid N-acyltransferase in red seabream is not able to distinguish taurine and D-cysteinolic acid as the substrate, probably because of their structural similarity. Consequently, D-cystenolic acid conjugated bile acids found in the bile of wild red seabream were thought to be synthesized in the liver of the fish utilizing the unusual amino acid, which originated from foods, prior to secretion into the bile.

Acyltransferases↗

PubMed1993

Effects of aluminium-containing antacid on bioavailability of ofloxacin following oral administration of pivaloyloxymethyl ester of ofloxacin as prodrug.

We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al3+, Mg2+, Ca2+, or Fe2+ in the gastrointestinal tract. This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes. In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion. Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX. Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits. The area under the plasma concentration-versus-time curve from zero to 24 h (AUC0-24h) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC0-24h values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone. These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations.

Administration, Oral↗

PubMed1993

[The effect of the eradication of H. pylori on the intractable ulcer].

On 25 cases (gastric ulcer 14 cases and duodenal ulcer 11 cases) of the intractable ulcer which was H. pylori-positive, we eradicated H. pylori. The eradication was done during 14 days by a triple therapy: bismuth subnitrate 2.0 g, metronidazole 0.75 g, AMPC 0.75 g/day). All cases were confirmed to be eradicated by culture and microscopic examination. 24 cases (gastric ulcer 13/14 and duodenal ulcer 11/11) were confirmed to be completely cured. After the eradication, we ceased the maintenance therapy by H2RA and followed them up, however, no ulcer relapses were found up to 9 months. It was considered that the eradication against H. pylori was a very effective method to the intractable ulcer.

Ampicillin↗

PubMed1993

Bile acid sulfonates alter cholesterol gallstone incidence in hamsters.

The prevention of cholesterol gallstone formation by three bile acid analogs, sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24- sulfonate, sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane-24-sulfonate, was examined in a hamster model of cholesterol cholelithiasis. Sodium taurochenodeoxycholate, sodium tauroursodeoxycholate and sodium taurohyodeoxycholate were studied simultaneously for comparison. Gallstones and cholesterol crystals were induced in 14 of 15 hamsters fed a bile acid-free, semipurified lithogenic diet containing 0.3% cholesterol and 4% butterfat for 6 wk. The addition of 0.1% sodium taurochenodeoxycholate and sodium tauroursodeoxycholate to the lithogenic diet had little effect on the formation of gallstones or biliary cholesterol crystals. In contrast, sodium 3 alpha,7 alpha-hydroxy-5 beta-cholane-24- sulfonate and sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate, when fed at the same dose, prevented cholesterol gallstone formation significantly. Sodium taurohyodeoxycholate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane- 24-sulfonate inhibited cholesterol gallstone formation effectively. The cholesterol saturation index of bile was greater than 1.00 in all groups, with the exception of the group fed sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate. Liver and serum cholesterol levels tended to be lower in most of the groups that were fed bile acids. This effect was most pronounced in the animals receiving sodium taurohyodeoxycholate. At the end of the experiment, the administered sulfonate analogs were detected in gallbladder bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa.

A relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa was studied in 75 patients with duodenal ulcer and nine with endoscopically normal duodenal mucosa. A biopsy of the duodenal bulb in each patient was used for both detection of H. pylori and histological assessment of acute inflammation [polymorphonuclear leukocyte (PMN) infiltration and regenerative changes of the duodenal epithelial cells]. Biopsies with regenerative changes showed a marked PMN infiltration, regardless of the duodenal H. pylori status. In biopsies without regenerative changes, H. pylori colonization was closely associated with PMN infiltration. Acute inflammation in the duodenal mucosa surrounding ulcers is caused mainly by acid, but our data suggest that H. pylori is another important factor in the development of PMN infiltration in the duodenal mucosa.

Biopsy↗

PubMed1993

Metabolism of sulfonate analogs of ursodeoxycholic acid and their effects on biliary bile acid composition in hamsters.

The metabolism of sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate was studied in hamsters. In bile fistula animals these sulfonate analogs of ursodeoxycholic acid were absorbed mainly from the terminal ileum and secreted rapidly into the bile without biotransformation or conjugation. After oral administration, the sulfonate analogs were excreted in the feces at the same rate as chenodeoxycholic acid and its metabolic products. The intestinal microorganisms transformed chenodeoxycholic acid largely into lithocholic acid; the sulfonate analogs were completely resistant to biotransformation. After a 2-week feeding period, the sulfonate analogs of ursodeoxycholic acid accounted for 24.0% and 16.9% of total biliary bile acids. These sulfonates did not affect the proportions of the natural bile acids in the bile, and the ratio of glycine-conjugated bile acids to taurine-conjugated bile acids was not altered by feeding the sulfonates. In contrast, when ursodeoxycholic acid was fed, the proportions of the natural bile acids and the glycine/taurine ratio were changed. These results suggest that the sulfonate analogs had no profound effect on endogenous bile acid metabolism and did not cause a depletion of the hepatic taurine pool during enterohepatic circulation. The sulfonates had no effect on intestinal cholesterol absorption and serum cholesterol levels.

Animals↗