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Biomedical subjects

Katsutoshi Terasawa

Publications and source records attributed to Katsutoshi Terasawa.

At least 19 recordsLinked to original sources

Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis.

BACKGROUND: The number of patients suffering from metabolic syndrome is increasing rapidly. Metabolic syndrome causes severe pathological changes in various organs, including the liver, and its main phenotype is nonalcoholic fatty liver disease (NAFLD). NAFLD has a broad spectrum ranging from simple fatty change to severe steatohepatitis with marked fibrosis. Recently, several experimental animal models for NAFLD have been proposed. However, most were established by rather artificial conditions such as genetic alteration. In the present study, we tried to establish a unique animal model mimicking some of the physiopathological features of NAFLD using high-cholesterol-fed rabbits. METHODS: Male rabbits fed with standard rabbit food containing 1% cholesterol for 8 weeks and 12 weeks were compared to controls (six rabbits/group). The weight of food was strictly restricted to 100 g/rabbit per day. RESULTS: Body weights and fasting plasma insulin levels showed no significant differences among the groups. In contrast, characteristic fine fibrosis was extended from perivenular to pericellular areas, and microvesicular fatty change with ballooning degeneration was observed in perivenular areas in livers of the cholesterol-fed rabbits. Increase of serum cholesterol level, activation of hepatic stellate cells, and exposure to oxidative stress were also recognized. CONCLUSIONS: Cholesterol-fed rabbits share several physiopathological features of NAFLD. Because this model did not show insulin resistance or obesity, it may be useful for elucidating the mechanism of NAFLD related mainly to hyperlipidemia.

Animals↗

Effect of d-pseudoephedrine on cough reflex and its mode of action in guinea pigs.

d-Pseudoephedrine (PSE) is one of the main ingredients of Ephedrae herba. Although PSE is widely applied for patients with a common cold and upper respiratory inflammation as a decongestant, the effects of PSE on cough have never been reported. In this study, we investigated the antitussive effects of intraperitoneal injection of PSE on the cough reflex induced by microinjection of citric acid into the larynx of guinea pigs. PSE decreased the number of cough reflexes dose-dependently (-18.3 +/- 5.0% at 20 mg/kg, P<0.05; -41.1 +/- 7.2% at 60 mg/kg, P<0.01). Furthermore, PSE (60 mg/kg) increased the threshold intensity for inducing fictive cough by electrical micro-stimulation of the nucleus tractus solitarius (+72.7 +/- 8.4%, P<0.01). On the afferent discharge of the superior laryngeal nerve, PSE suppressed the increases of amplitude and frequency when stimulated by citric acid at laryngeal mucosa. These results demonstrate that PSE possesses an antitussive effect that might be derived from both central and peripheral actions.

Animals↗

Effects of eppikahangeto, a Kampo formula, and Ephedrae herba against citric acid-induced laryngeal cough in guinea pigs.

To evaluate the efficacy of three common antitussive Kampo formulas, eppikahangeto (EPP), bakumondoto (BAK), and shoseiryutogomakyokansekito (SGM), a new cough model of guinea pig was used, which could specifically induce a laryngeal cough by microinjection of citric acid solution into the larynx. Kampo extract was dissolved in water and the animals were given access ad libitum for 3 days, and then the number of coughs during 10 min was counted. EPP extract decreased the number of coughs dose-dependently (0.3% extract, -22.9 +/- 6.6%, P<0.01; 1.0% extract, -32.4 +/- 5.5%, P<0.01). BAK extract and SGM extract had no significant effect. Intraperitoneal injection of codeine (60 mg/kg) also decreased the number of coughs (-36.1 +/- 9.1%, P<0.05). Furthermore, Ephedrae herba (EH) extract reduced the number of coughs (-18.3 +/- 6.0%, P<0.05), but the extract of EPP without EH did not. These results suggest that EPP has an antitussive effect against laryngeally-induced cough in guinea pigs, and the crucial herbal medicine is EH.

Animals↗

Macrophage-mediated inhibitory effect of Zingiber officinale Rosc, a traditional oriental herbal medicine, on the growth of influenza A/Aichi/2/68 virus.

The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 approximately 100 microg/ml) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mphi) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-alpha was gradually accumulated in ZOR-CM by the induction of TNF-alpha mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-alpha after the formation of an immune complex with anti-TNF-alpha monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-alpha.

Animals↗

Juzentaihoto, a Kampo medicine, enhances IL-12 production by modulating Toll-like receptor 4 signaling pathways in murine peritoneal exudate macrophages.

Juzentaihoto (TJ-48), a Kampo medicine, has been reported to affect the immune system. Although toll-like receptors (TLRs) have been identified as receptors of innate immunity, the effects of TJ-48 on TLR signaling pathways have not been thoroughly investigated. Here we evaluated the effects of TJ-48 on TLR4 signaling pathways. Peritoneal exudate macrophages (PEMs) isolated from mice orally administered TJ-48 for 11 days were stimulated with lipopolysaccharide (LPS), a ligand of TLR4, in vitro. Production of IL-12 p40 was significantly augmented in TJ-48-treated PEMs compared with that in vehicle PEMs, without affecting the surface expression of TLR4. Treatment with chemical inhibitors of NF-kappa B and p38 mitogen-activated protein kinases (MAPKs) in vitro inhibited LPS-induced IL-12 production, whereas JNK and ERK inhibitors increased IL-12 production. Immunoblotting with phosphorylation-state specific antibodies demonstrated that TJ-48 differentially affected LPS-induced phosphorylation of NF-kappa B and MAPKs. In PEMs treated with TJ-48, LPS-induced phosphorylation of p65 NF-kappa B and p38 MAPK was augmented, while that of JNK and ERK was attenuated compared with those in vehicle PEMs. These results suggest that selective modulation of the TLR4 signaling pathways by TJ-48 is involved in enhanced production of IL-12 in PEMs.

Administration, Oral↗

The effect of fish oil on physical aggression in schoolchildren--a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The aim of the study was to investigate whether fish oil supplementation affected Japanese schoolchildren's behavior, with changes in aggression over time as the primary endpoint. DESIGN AND SUBJECTS: A placebo-controlled double-blind study with 166 schoolchildren 9-12 years of age was performed. The subjects of the fish oil group (n=83) took fish oil-fortified foods (bread, sausage and spaghetti). These foods were provided in amounts such that each subject in the fish oil group had an intake of 3600 mg of docosahexaenoic acid+840 mg of eicosapentaenoic acid (EPA)/week for 3 months. The rest (the controls, n=83) took control supplements. At the start and end of the study, psychological tests were performed to assess their aggression. RESULTS: Physical aggression assessed by Hostility-Aggression Questionnaire for Children in girls increased significantly (median: 13 to 15, n=42) in the control group and did not change (13 to 13, n=43) in the fish oil group with a significant intergroup difference (P=.008) with baseline as covariate. The changes in physical aggression scores over time and those of the ratio of EPA/arachidonic acid in RBC (DeltaEPA/AA) were significantly correlated in girls who agreed to blood collection (r=-.53, P=.01, n=23). On the contrary, there were no significant changes in physical aggression in boys. Aggression against others (extraggression) assessed by Picture Frustration Study did not change in the control group (median: 5 to 5) but increased significantly in the fish oil group (4 to 5) with a significant intergroup difference (P=.02) with baseline as covariate. These changes in extraggression might be explained partly by significantly lower baseline values of extraggression in the fish oil group (P=.02) than in the control group. There were no significant correlations between Deltaextraggression and DeltaEPA/AA in blood-sampled children (n=49). Impulsivity of girls assessed by parents/guardians using the diagnostic criteria for attention deficit/hyperactivity disorder of DSM-IV was reduced in the fish oil group (1 to 0) with a significant (P=.008) intergroup difference from the control group (1 to 1). There were no significant correlations between Deltaimpulsivity and DeltaEPA/AA in blood-sampled girls. In males, impulsivity reduced in both groups without any intergroup differences. CONCLUSION: There is a possibility that changes in fatty acid nutrition might affect physical aggression especially in girls.

Aggression↗

Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: We previously reported that administration of fish oil rich in docosahexaenoic acid (DHA) increased the plasma ratio of epinephrine to norepinephrine (NE) at rest in young adults who were under chronic stress and that this effect was achieved mainly through depression of NE. However, not many reports have documented the effects of eicosapentaenoic acid (EPA) and DHA on blood catecholamine levels in healthy humans. Therefore, we performed another intervention study to test their effect on catecholamines with healthy subjects under no chronic stress. METHODS: Twenty-one healthy young adults (15 men and 6 women) were randomly assigned to an omega-3 group (n = 9) or a control group (n = 12) in a double-blind manner. Twenty capsules of shellfish-derived lipids containing 762 mg of EPA plus DHA per day were administered to the omega-3 group for 2 mo. The controls took the same amount of placebo capsules. Fasting blood samples after a 30-min rest with a catheter in a forearm vein were obtained at the start and the end of the study for catecholamine measurements. RESULTS: EPA but not DHA concentrations in red blood cells significantly increased in the omega-3 group compared with the control group (P < 0.001). Plasma NE concentrations were significantly decreased in the omega-3 group (from 1.49 +/- 0.39 nmol/L to 1.05 +/- 0.14 nmol/L) compared with the control group (from 1.12 +/- 0.24 nmol/L to 1.39 +/- 0.32 nmol/L) with analysis of covariance (P < 0.001). The differences remained significant (P = 0.01) even after deletion of three subjects in the omega-3 group who had the highest baseline NE values and one in the control group who had the lowest baseline NE value to nullify a significant baseline differences in NE between groups. CONCLUSION: This study demonstrated that EPA plus DHA supplementation lowered plasma NE concentrations in normal volunteers even at the small dose of 762 mg of EPA plus DHA per day. This effect of EPA plus DHA to lower plasma NE concentrations may be important to understand some of the effects of fish oils on diseases.

Adolescent↗

Reduction of perception of chronic fatigue in an observational study of patients receiving 12 weeks of Kampo therapy.

OBJECTIVE: The aim of this study was to observe the influence of Kampo therapy on latent chronic fatigue of patients with chronic diseases. SUBJECTS: One hundred and seventy-three (173) consecutive patients with chronic diseases came to our department for the first time. DESIGN: This was a prospective study. Patients were divided into two groups: a chronic fatigue group (CFG) and a nonchronic fatigue group (NCFG). Based on Kampo diagnosis, both groups were prescribed Kampo formulae as an extract or decoction for 12 weeks. OUTCOME MEASURES: By using questionnaires, patients were assessed concerning their physical and mental types of fatigue, their sleep situation, and their attitude toward work or housekeeping, both before and after 12 weeks of treatment, according to Kampo diagnosis. RESULTS: The mental fatigue, physical fatigue, and sleep scores of both groups, and the work score of CFG, were decreased. The rate of reduction of the fatigue score was significantly greater in CFG than in NCFG. The factor responsible for this difference in fatigue score was physical fatigue. CONCLUSIONS: A reduction of the perception of chronic fatigue was observed in patients receiving 12 weeks of Kampo therapy.

Adolescent↗

Induction of inducible nitric oxide (NO) synthase mRNA and NO production in macrophages infected with influenza A/PR/8 virus and stimulated with its ether-split product.

We investigated the inductive activity of infective influenza A/PR/8/34 (PR8) virus and its ether-split product (ESP) on the expression of inducible nitric oxide (NO) synthase (iNOS) and NO production in RAW264.7 (RAW) cells, a murine macrophage (M psi) cell line, and thioglycolate-elicited peritoneal M psi (TPM). In both cells, PR8 virus infection induced iNOS mRNA between 4 hr and 24 hr, attaining a peak value at 12 hr. In correlation with induction of iNOS mRNA, NO amounts increased significantly from 12 to 24 hr. Moreover, this study demonstrated that ESP with the same hemagglutination titer as PR8 virus could induce iNOS mRNA and NO production, although the inductive activity of ESP was weaker than that of PR8 virus. Considering the dual role (beneficial and detrimental roles) of NO on certain inflammatory disorders and virus infections, the inductive activity of influenza virus on the iNOS-mediated NO production independent of its infectivity might contribute to a modification of influenza virus infection.

Animals↗

Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits.

In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol and 1% KBG, and the vitamin E group was fed standard rabbit chow containing 1% cholesterol and vitamin E (450 mg/1000 g). All four groups were kept on these diets for 8 weeks. At the end of the experiments, the percentage of surface area of the total thoracic aorta with visible plaque was significantly reduced in the OGT and KBG groups. The serum thiobarbituric acid reactive substances of the vitamin E group showed a significantly low value compared with the control group, whereas the serum lipid peroxide levels of the OGT and KBG groups were considerably lower than that of the control groups as well as that of the vitamin E group. Furthermore, the urinary 8-hydroxydeoxyguanosine levels of the OGT and KBG groups were considerably lower than that of the vitamin E group. These results suggest that OGT and KBG prevent the progression of atheromatous plaque by creating a sounder antioxidant defense system than vitamin E.

Animals↗

Inhibitory effects of Stephania tetrandra S. Moore on free radical-induced lysis of rat red blood cells.

Crude preparations of Stephania tetrandra S. MOORE (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. In this study, we demonstrated that ST in vitro protects red blood cells from 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 10 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of ST that exerts a scavenging effect on free-radicals. Three representative alkaloids, tetrandrine, fangchinoline, and cyclanoline, isolated from ST, were found to have inhibitory activities against AAPH-induced lysis of red blood cells (RBC). Furthermore, the ingestion of 200 mg of ST extract was associated with a significant increase in free-radical scavenging effect of plasma in rats. These results suggest that ST as antioxidant inhibits AAPH-induced hemolysis of RBC both in vitro and in vivo.

Alkaloids↗

Inhibitory effects of triterpenes isolated from Chuling (Polyporus umbellatus Fries) on free radical-induced lysis of red blood cells.

Chuling, sclerotia of Polyporus umbellatus FRIES, has long been used for urological disorders in traditional medicine. In this study, we demonstrated that Chuling in vitro protects red blood cells from 2,2-azo-bis(2-amidinopropane)dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 50 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of Chuling with scavenging effect on free radicals. Triterpene carboxylic acids isolated from the methanol extract of Chuling, namely, polyporusterone A and polyporusterone B, were found to have inhibitory activities against AAPH-induced lysis of red blood cells. The anti-hemolytic effect was significantly stronger in polyporusterone B compared with polyporusterone A. Furthermore, the ingestion of 150 mg of Chuling was associated with a significant increase in free-radical scavenging effect of plasma in rats.

Dose-Response Relationship, Drug↗

Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China.

BACKGROUND: Epidemiologic studies show that low fish intake is a risk factor of suicidality; however, there are no case-control studies investigating suicide attempt risk and tissue n-3 fatty acid levels. METHODS: We recruited 100 suicide-attempt cases and another 100 control patients injured by accidents who were admitted to three hospitals affiliated with Dalian Medical University in Dalian, China. Case and control subjects were matched for age, gender, and smoking status. Those who were inebriated at the time of hospitalization were excluded. Blood was sampled immediately after admission to a hospital. Washed red blood cells (RBCs) were obtained, and the fatty acid composition of the total RBC phospholipid fraction was analyzed by gas chromatography. RESULTS: Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p <.0001). When the highest and lowest quartiles of EPA in RBC were compared, the odds ratios of suicide attempt was.12 in the highest quartile (95% confidence interval:.04-.36, p for trend =.0001) after adjustment for possible confounding factors CONCLUSIONS: Our findings suggest that low n-3 fatty acid levels in tissues were a risk factor of suicide attempt. Further studies including intervention with fish oil are warranted.

Adult↗