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Biomedical subjects

T Matsuhashi

Publications and source records attributed to T Matsuhashi.

At least 19 recordsLinked to original sources
PubMed2005

New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline.

BACKGROUND: In functional gastrointestinal (GI) disorders including functional dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent of contributions of psychosomatic factors. As a therapy for IBS patients, the effectiveness of antidepressants has been reported. AIM: In this study, we evaluated the efficacy of H2-receptor antagonist (famotidine) and 5-HT4 receptor agonist (mosapride citrate). In addition, the effect of antidepressants was assessed as the second-step therapy. METHODS: Patients complaining upper GI symptoms were diagnosed as FD excluding organic diseases. Randomized patients received 20 mg/day of famotidine or 15 mg/day of mosapride citrate for 4 weeks and the efficacy was compared between the two groups based on a 10-point visual analogue scale. When symptoms were not relieved (score improvement 0-2 points), patients received amitriptyline (30 mg/day) or no medication for 4 weeks randomly. Patients who had depression in psychological test (SDS) were omitted. RESULTS: As the first-step therapy, both famotidine and mosapride showed beneficial effects regardless of FD subtypes, age and gender. The efficacy of these two drugs in relieving FD symptoms was not significantly different. In patients who failed in the first-step therapy, amitriptyline showed beneficial effects. CONCLUSIONS: These findings might be clinically important in view of the efficient relief of symptoms in FD patients.

Aged↗
PubMed1999

Microevolution of the mitochondrial DNA control region in the Japanese brown bear (Ursus arctos) population.

We investigated nucleotide sequences of the mitochondrial DNA control region to describe natural genetic variations and to assess the relationships between subpopulations of the brown bear Ursus arctos on Hokkaido Island, Japan. Using the polymerase chain reaction product-direct sequencing technique, partial sequences (about 930 bases) of the control region were determined for 56 brown bears sampled throughout Hokkaido Island. A sequence alignment revealed that the brown bear control region included a variable sequence on the 5' side and a repetitive region on the 3' side. Phylogenetic trees reconstructed from the 5' variable region (696-702 bases) exhibited 17 haplotypes, which were clustered into three groups (Clusters A, B, and C). The distribution of each group did not overlap with those of the others, and the three different areas were located in separate mountainous forests of Hokkaido Island. Furthermore, most of the phylogenetically close haplotypes within each group were distributed geographically close to each other. In addition, the 3' repetitive region (arrays of 10 bases) exhibited a much faster mutation rate than the 5' variable region, resulting in heteroplasmy. Such mitochondrial DNA divergence in each group could have occurred after the brown bears migrated from the continent to Hokkaido and became fixed in the different areas.

Animals↗
PubMed1998

Complete suppresion of ethanol-induced formation of megamitochondria by 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-OH-TEMPO).

An attempt has been made to suppress the ethanol-induced formation of megamitochondria (MG) in the rat liver by 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-OH-TEMPO), a free radical scavenger, and by allopurinol (AP), a xanthine oxidase inhibitor. Changes observed in the liver of animals given ethanol (EtOH) for 1 month were remarkable decreases both in the body weight gains during the course of the experiment and in the liver weight at the time of sacrifice compared to those of the control; remarkable increases in the level of thiobarbituric acid reactive substances and lipid soluble fluorophores both in microsomes and mitochondria; decreases in the content of cytochrome a+a3 and b and lowered phosphorylating ability of mitochondria; and formation of MG in the liver. A combined treatment of animals with EtOH plus 4-OH-TEMPO completely suppressed the formation of MG in the liver induced by EtOH and distinctly improved the changes caused by EtOH, as specified above, while AP partly suppressed the MG formation. Results described herein provide additional insight into chronic hepatotoxicity of EtOH besides that previously reported. A novelty of the present work is that we were able for the first time to demonstrate reversibility of EtOH-mediated ultrastructural changes of the liver by a simple administration of aminoxyl-type free radical scavenger, 4-OH-TEMPO. Our results suggest that free radicals may be involved in the mechanism of the formation of MG induced by EtOH.

Allopurinol↗
PubMed1997

Suppression of the formation of megamitochondria by scavengers for free radicals.

In the present study we have attempted to suppress the formation of megamitochondria by scavengers for free radicals since conditions for the formation of megamitochondria are often intimately related to the generation of free radicals. We employed three different experimental conditions to induce megamitochondria in the liver: ethanol, hydrazine and chloramphenicol (CP). Scavengers for free radicals tested were: alpha-tocopherol, coenzyme Q10(CoQ10) and 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl(4-OH-TEMPO). Allopurinol (AP), a xanthine oxidase inhibitor, was also tested. Results obtained were as follows. (1) Changes observed in the liver of animals treated with ethanol, hydrazine or CP were: formation of megamitochondria; decreases in the body weight and the weight of the liver; remarkable increases in the level of lipid peroxidation; increases in the activity of xanthine oxidase. (2) 4-OH-TEMPO was most effective in improving these changes. A mechanism of the formation of megamitochondria is proposed stressing the role of free radicals in the mechanism.

Allopurinol↗
PubMed1997

Role of free radicals in the mechanism of the hydrazine-induced formation of megamitochondria.

The effect of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl(4-OH-TEMPO), a scavenger for free radicals, and 4-hydroxypyrazolo [3,4-d(pyrimidine)allopurinol], a xanthine oxidase inhibitor, on the hydrazine-induced changes of mitochondrial ultrastructure and those in the antioxidant system of the liver were investigated using rats as experimental animals. Animals were placed on a powdered diet containing 0.5% hydrazine for 7 d in the presence and absence of a combined treatment with 4-OH-TEMPO or allopurinol. Results obtained were as follows. 4-OH-TEMPO completely prevented the hydrazine-induced formation of megamitochondria in the liver, while it was partly prevented by allopurinol. The following changes observed in hydrazine-treated animals were improved almost completely by 4-OH-TEMPO:decreases in the body weight and liver weight; lowered rates of ADP-stimulated respiration and coupling efficiency of hepatic mitochondria; remarkable elevation of the level of lipid peroxidation. Improving effects of allopurinol were incomplete. The present results suggest that free radicals may play a key role in the mechanism of the hydrazine-induced formation of megamitochondria and that a part of free radicals generated during the hydrazine intoxication is ascribed to the degradation of purine nucleotides via xanthine oxidase. A general mechanism of the megamitochondria formation induced in various pathological conditions besides the case of hydrazine are discussed.

Allopurinol↗
PubMed1996

Mechanism of the formation of megamitochondria in the mouse liver induced by chloramphenicol.

Correlation between chloramphenicol-induced formation of megamitochondria in the mouse liver and oxidative stress was studied by lipid peroxidation analysis and electron microscopic technique. Chloramphenicol suppressed increases in the body weight and liver weight of experimental animals and at the same time induced a remarkable increase in lipid peroxidation in the liver during the formation of megamitochondria. A spin trapping agent, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, abolished all these changes induced by chloramphenicol. Namely, both the body weight and liver weight of chloramphenicol-treated animals stayed at the same levels as those of the control, and the formation of megamitochondria was completely suppressed. Allopurinol, a xanthine oxidase (EC 1.2.3.2) inhibitor, partly inhibited the changes induced by chloramphenicol, as described above. These results suggest that chloramphenicol-induced formation of megamitochondria is not simply ascribed to the suppression of the dividing process of mitochondria due to lowered protein synthesis in mitochondria but is intimately related to oxidative stress. Furthermore, the results obtained with allopurinol may indicate that enhanced levels of lipid peroxidation observed in chloramphenicol-treated animals are partly due to enhanced rate of the degradation of purine nucleotides catalyzed by xanthine oxidase.

Allopurinol↗
PubMed1996

In vivo evaluation of a fluorine-acryl-stylene-urethane-silicone antithrombogenic coating material copolymer for intravascular stents.

RATIONALE AND OBJECTIVES: We evaluated the effectiveness of a fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer as an antithrombogenic coating material for intravascular stents in dogs. METHODS: FASUS copolymer-coated stents were placed in the right iliac veins, and uncoated 304 stainless steel stents were placed in the left iliac veins. We examined platelet deposition, microthrombus formation, and neointimal hyperplasia 4 weeks after stent placement by measuring the activity of 111In-labeled platelets, by using scanning electron microscopy, and by measuring neointimal thickness. RESULTS: Platelet deposition was significantly decreased on coated than on uncoated stents (p < .05). A less pronounced increase in red blood cell deposition was observed at the sites of the coated than uncoated stents (p < .05). Neointimal thickness 4 weeks after stent placement also was significantly less at the sites of the coated stents (0.27 +/- 0.08 mm versus 0.48 +/- 0.23 mm, p < .05). CONCLUSION: FASUS copolymer coating over the vascular stent is effective for preventing thrombus formation and neointimal hyperplasia.

Animals↗
PubMed1996

Effect of alcohol on tumor growth of hepatocellular carcinoma with type C cirrhosis.

To investigate the influence of alcohol intake on tumor growth of hepatocellular carcinoma (HCC) in patients with type C cirrhosis, we examined the tumor volume doubling time (TVDT) of 35 nodules from 35 cases of HCC, calculated through ultrasonographic imaging. The patients were divided into two groups according to their drinking habit; 21 habitual drinkers (alcohol group; 80g ethanol/day for 5 years), and 14 patients without alcohol abuse (non alcoholic group). The average value of TVDT in the alcoholic group was 78 +/- 47 days, although that of the non alcoholic group was 142 +/- 60 days. A statistically significant difference (p < 0.01) was found between the two groups. Of the 21 habitual alcohol drinkers, 8 refrained from drinking after detection of HCC; their TVDT was about 30 days shorter than those who continued alcohol intake. In conclusion we found that alcohol intake was closely related to the tumor growth of HCC in patients with type C cirrhosis.

Adult↗
PubMed1996

An evaluation of hepatic ultrasound speed in injury models in rats: correlation with tissue constituents.

The speed of sound through the livers of 32 male Sprague-Dawley rats was measured. The study population consisted of four experimental groups: control, acute liver injury induced by carbon tetrachloride, fatty liver induced by a choline-deficient diet, and liver cirrhosis induced by administration of N-diethylnitrosamine. To examine possible correlations between the speed of sound and liver histology, biochemical measurements of the water, fat, and collagen content were made. The aim of the present study was to determine the effects of the characteristics of diseased liver tissue on the speed of sound, by studying the tissue constituents biochemically and by using a more accurate measurement of the speed of sound. The sound speed was 1591.6 +/- 6.7 m/s in the acute liver injury group, 1531.4 +/- 18.4 m/s in the fatty liver group, and 1624.9 +/- 6.7 m/s in the liver cirrhosis group. No significant correlation existed between the speed of sound and the water content in all groups taken together, whereas a good correlation was found in the fatty liver group (P < 0.0001, r = -0.858) and in cirrhosis (P < 0.0001, r = 0.760) when the groups were examined separately. These results indicate that the speed of sound is useful for diagnosing fatty liver for predicting the fat content.

Animals↗
PubMed1995

Studies on urea synthesis in the liver of rats treated chronically with ethanol using perfused livers, isolated hepatocytes, and mitochondria.

Changes in urea synthesis in the liver of rats treated with 32% ethanol in the drinking water for up to 6 months were studied using perfused livers, isolated hepatocytes, and mitochondria. Results obtained from ethanol-treated rats are summarized as follows: (1) the mitochondria of the hepatocytes of rats treated with ethanol for 2 months or longer became enlarged to various degrees, (2) the levels of ammonia in the serum remained within a normal range, while those in liver tissue were elevated compared with the control, (3) urea synthesis from ammonia in perfused livers was decreased markedly, while that from citrulline remained in the normal range, (4) the activities of carbamyl phosphate synthetase (CPS; EC 2.7.2.5) and ornithine transcarbamylase (OTC; EC 2.1.3.3) in mitochondria were unchanged compared with those of the control, and (5) the levels of ATP in liver tissue and the ability of mitochondria to synthesize ATP were decreased markedly compared with the control. Both the level of ATP in the hepatocytes and the synthesis of urea from ammonia by perfused livers of rats treated with ethanol were resistant to externally added ethanol, while those of control animals were severely affected. These results suggest that the intracellular level of ATP is intimately related to urea synthesis in both control and ethanol-treated animals, and lowered levels of ATP may be a key factor in the suppression of urea synthesis in ethanol-treated animals.

Adenosine Triphosphate↗
PubMed1994

Further studies on physicochemical properties of mitochondrial membranes during the formation process of megamitochondria in the rat liver by hydrazine.

Physicochemical properties of lipids extracted from hepatic mitochondria of rats fed with 1% hydrazine diet for 3 days (3H-mitochondria) and 7 days (7H-mitochondria) were studied using differential scanning calorimetry and the fluorescence polarization measurements. Results obtained from lipids extracted from 3H-mitochondria were as follows: (1) Thermotropic phase transition temperatures (Tm) were elevated with a distinct increase in transition enthalpy (delta H) compared to those of the control due to increases in relative amounts of phosphatidylethanolamine (PE) and phosphatidylserine (PS) in phospholipid species. (2) Tm in lipids and phospholipids extracted from 3H-mitochondria was elevated with decreases in delta H after the addition of Ca2+, whereas delta H of the control was increased after the addition of Ca2+. (3) Phosphatidylcholine (PC) liposomes containing PE or PS at concentrations corresponding to PE/PC or PS/PC ratio in 3H-mitochondria showed elevations of transition temperatures with decreases in delta H values after the addition of Ca2+, whereas those containing PE or PS ratio at concentrations corresponding to PE/PC or PS/PC in the control mitochondria showed increases in delta H values after the addition of Ca2+. (4) There were essentially no changes in membrane fluidity between lipids extracted from 3H-mitochondria and those extracted from the control mitochondria. Addition of Ca2+ to lipids extracted from 3H-mitochondria, however, caused elevation of membrane fluidity while those extracted from the control mitochondria showed no changes in membrane fluidity after the addition of Ca2+. (5) Increases in the ratio of unsaturated fatty acids to saturated fatty acids (U/S ratio) in phospholipids extracted from 3H-mitochondria were found to be mainly due to those in PS. These data may suggest that hydrazine modifies the membrane of mitochondria favorable for the membrane fusion via enhanced acidic phospholipid-Ca2+ interactions.

Animals↗
PubMed1994

Treatment of symptomatic hepatic cysts by percutaneous instillation of minocycline hydrochloride.

Nine patients with 16 symptomatic nonneoplastic congenital hepatic cysts were treated prospectively by ultrasonically guided percutaneous minocycline hydrochloride injection, and the usefulness of this treatment was evaluated. Seven of the patients had multiple hepatic cysts, and two solitary cysts. All the patients were women, ranging in age from 36 to 81 years. After cystic fluid had been aspirated with a 21-gauge PTC needle, minocycline hydrochloride was injected into all the cysts. The minocycline hydrochloride was dissolved in saline at a concentration of 200 mg in 9 ml, and mixed with 1 ml of 2% mepivacaine hydrochloride. The total quantity of minocycline hydrochloride injected varied from 100 mg to 1200 mg per hepatic cyst, depending on its size. Total or subtotal regression of the cysts was observed in all patients during follow-up periods ranging from 15 to 35 months. Seven patients became symptom-free, one showed symptom reduction, and one showed no change in symptoms. Minor side effects, eg, transient abdominal pain, slight right shoulder pain, and temperature elevation, were noted in three patients respectively. On the basis of these results, we conclude that ultrasonically guided percutaneous minocycline hydrochloride injection is useful for the treatment of symptomatic hepatic cysts.

Adult↗
PubMed1993

Potentiating effects of organomercuries on clastogen-induced chromosome aberrations in cultured Chinese hamster cells.

Mercury compounds are among the most serious environmental pollutants. In this communication, the potentiating effects of organic and inorganic mercuries on clastogen-induced chromosome aberrations were studied in Chinese hamster CHO K1 cells. Post-treatment with monoalkylated mercuries--methyl mercuric chloride (MeHgCl) and ethyl mercuric chloride (EtHgCl)--increased the number of breakage- and exchange-type aberrations induced by 4-nitroquinoline 1-oxide (4NQO) and methyl methanesulfonate. With the DNA crosslinking agents mitomycin C (MMC) and cisplatin, MeHgCl enhanced both types of aberrations while EtHgCl enhanced breakage-type aberrations only. Since these monoalkylated mercuries did not show clastogenic effects by themselves under the present experimental conditions, the increases in chromosome aberrations were not additive. Dialkylated mercuries (dimethyl mercury and diethyl mercury) and inorganic mercuries (HgCl and HgCl2) did not show any potentiating effects. When MMC- or 4NQO-treated cells were post-treated with MeHgCl during the G1 phase, both breakage- and exchange-type aberrations were enhanced. Treatment with EtHgCl during the G1 phase also enhanced both types of aberrations induced by 4NQO. With MMC, however, G1 treatment with EtHgCl did not show any potentiating effect. MeHgCl and EtHgCl treatments during the G2 phase enhanced breakage-type aberrations only. Based on these results, the following possible mechanisms for potentiation of clastogenicity by monoalkylated mercuries were suggested; (1) they interfere with repair of base lesions induced by 4NQO and MMS during the pre-replicational stage, thereby increasing unrepaired DNA lesions which convert into DNA double-strand breaks in S phase, (2) MeHgCl (but not EtHgCl) also inhibits repair of crosslinking lesions during the pre-replicational stage, and (3) their G2 effects enhance breakage-type aberrations only.

4-Nitroquinoline-1-oxide↗