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Male 5-week-old F344 rats were fed four types of experimental diet with different Ca and protein sources for 30 days, and the effect of feeding retort-treated herring bone on Ca absorption and bone metabolism were examined. The experimental diets were as follows: AIN-93G (casein-based standard breeding diet) containing 0.5% Ca from CaCO3 (C); modified AIN-93G containing 0.25% Ca from CaCO3 (L); retorted herring meat with bone containing 0.25% Ca from edible bones (PHB); and retorted deboned herring meat containing 0.06% and 0.19% Ca from retorted bones and CaCO3 (PH). There was no difference in weight increase among the groups during the feeding period. The Ca absorption rate (CAR) in the PHB and PH groups after 4 weeks was slightly lower than that of L, whereas CAR did not differ between PHB and PH. Furthermore, the involvement of absorbed calcium in bone metabolism, as assessed using the bone turnover markers, did not differ between the PHB, PH, and L groups. In conclusion, fish bones rendered edible after retort treatment are a good source of Ca, the nutritional value of which is similar to that of CaCO3, indicating that retort treatment is a suitable cooking method for using fish as a Ca source.

Chum salmon myofibrillar protein (Mf) digested by pepsin-trypsin (dMf) was conjugated to alginate oligosaccharide (AO) through the Maillard reaction between the lysine residues in the dMf and the reducing end-groups of AO. The dMf-AO conjugate strongly suppressed the production of inflammatory cytokines, particularly tumor necrosis factor-α and interleukin-6, in lipopolysaccharide-stimulated murine macrophages. The anti-inflammatory effect was enhanced with increasing amounts of AO bound to dMf through the Maillard reaction, and the subsequent process of the Maillard reaction was involved in the enhancement of the anti-inflammatory activity. AO-conjugated peptides, the major anti-inflammatory components contained in the dMf-AO conjugate, were successfully recovered using isoelectric focusing without the use of carrier ampholytes (autofocusing); they were effectively concentrated in acidic peptide fractions, with the negative charge of the carboxyl groups of AO contributing to this separation. In conclusion, the combined use of AO conjugation and autofocusing is a useful method for producing novel anti-inflammatory peptides from fish Mf.

We previously reported that dietary supplementation with cholic acid (CA), the primary 12α-hydroxylated (12αOH) bile acid (BA), reduces plasma adiponectin concentration in rats. The aim of this study was to examine the distribution of adiponectin in the body of CA-fed rats and its influence on mucosal immunoglobulin A concentration in the intestine. Rats were fed a diet supplemented with or without CA (0.5 g CA/kg diet) for 13 weeks. A reduction in plasma adiponectin level was observed from week 3. At the end of the experiment, the CA diet reduced plasma adiponectin concentration both in the portal and aortic plasma. Accumulation of adiponectin was accompanied by an increase in cadherin-13 mRNA expression in the ileal mucosa of CA-fed rats. No increase was observed in adiponectin mRNA expression in the ileal and adipose tissues of the CA-fed rats. Immunoglobulin A concentration in the ileal mucosa was elevated in the CA-fed rats and was correlated with the ileal adiponectin concentration. 12αOH BAs may modulate mucosal immune response that are involved in the accumulation of adiponectin in the ileum.

Background Inbred strains are characterized by less genetic variation, which suggests usefulness of inbred strains for evaluations of various parameters. In this study, experimental reproducibility in several parameters was compared between an outbred Wistar rat and Wistar King A Hokkaido (WKAH/HkmSlc) rat, the inbred strain that is originated from Wistar rats. Methods Difference of variations was investigated in parameters of body compositions and liver functions such as body weight, liver weight, liver triglycerides (TG), liver cholesterol and plasma alanine aminotransferase activity (ALT) between WKAH rats and outbred Wistar rats by using the coefficient of variation (CV). Results There was no difference in the CVs of body weight and relative liver weight between WKAH and Wistar rats. The CVs of body weight and relative liver weight were below 10% in both WKAH and Wistar rats. The CVs of TG, cholesterol, and ALT in Wistar rats were between 30 and 40%, whereas those in WKAH rats were between 10 and 25%. A low CV level of TG was observed in WKAH rats compared to that in Wistar rats regardless of the duration of the experimental period in those rat strains. Conclusion The low CV values in metabolic parameters involved in liver functions in the inbred rats suggested an advantage of using inbred rather than outbred rats for the evaluation of liver lipid metabolism.

There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12 alpha-hydroxylated BAs to non-12 alpha-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4 beta-hydroxycholesterol (4 beta OH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4 beta OH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4 beta OH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12 alpha-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism.

Full-scale sea trials demonstrate a ship’s performance under real operating conditions to confirm whether a ship meets its specifications and requirements. The determination of the performance through a sea trial is the most important stage in the ship design cycle. If one is relying on measurements of propeller shaft power or fuel consumption, the distinction between the propeller and hull efficiencies may not be made. In order to be able to identify the propeller efficiency separate from the hull, full-scale propeller thrust should be accurately measured. In this study, full-scale measurements of the propeller thrust, torque, and revolution for a series of crude oil tankers and twin-skeg LNG carrier were conducted during the speed trials. Two different measuring systems, strain gauge and optical type, were implemented to compare the performance of sensors. As a result, it was shown that the strain gauge type-measuring device matched the model test results relatively well compared to the optical device. Above all, in the case of the optical device, it has been demonstrated that the zero setting is important to increase the accuracy of the full-scale measurements.

Intestinal bacteria are involved in bile acid (BA) deconjugation and/or dehydroxylation and are responsible for the production of secondary BA. However, an increase in the production of secondary BA modulates the intestinal microbiota due to the bactericidal effects and promotes cancer risk in the liver and colon. The ingestion ofBacillus coagulansimproves constipation via the activation of bowel movement to promote defaecation in humans, which may alter BA metabolism in the intestinal contents. BA secretion is promoted with high-fat diet consumption, and the ratio of cholic acid (CA):chenodeoxycholic acid in primary BA increases with ageing. The dietary supplementation of CA mimics the BA environment in diet-induced obesity and ageing. We investigated whetherB. coagulanslilac-01 and soya pulp influence both BA metabolism and the maintenance of host health in CA-supplemented diet-fed rats. In CA-fed rats, soya pulp significantly increased the production of secondary BA such as deoxycholic acid andω-muricholic acids, and soya pulp ingestion alleviated problems related to plasma adiponectin and gut permeability in rats fed the CA diet. The combination ofB. coagulansand soya pulp successfully suppressed the increased production of secondary BA in CA-fed rats compared with soya pulp itself, without impairing the beneficial effects of soya pulp ingestion. In conclusion, it is possible that a combination of prebiotics and probiotics can be used to avoid an unnecessary increase in the production of secondary BA in the large intestine without impairing the beneficial functions of prebiotics.

The term "megalo-saccharide" is used for saccharides with ten or more saccharide units, whereas the term "oligo-saccharide" is used for saccharides containing fewer than ten monosaccharide units. Megalo-type α-1,6-glucosaccharide (M-IM) is a non-digestible saccharide and not utilized by intestinal bacteria, suggesting that ingested M-IM may encounter ileum Peyer's patches that contains immune cells such as macrophages. Macrophages are responsible for antigen incorporation and presentation during the initial step of immune responses. We investigated whether M-IMs modulate macrophage functions such as cytokine production, nitric oxide production, cell viability, and phagocytosis. Primary macrophages collected from the rats were cultured with the existence of M-IM or lipopolysaccharides (LPS). M-IM and LPS induced the production of tumor necrosis factor α (TNFα), interleukin 6 (IL6), and nitric oxide in the primary macrophages. The gene expression profile of inflammatory factors including TNFα, IL6, and ILlβ in M-IM-stimulated cells was similar to that of LPS-stimulated cells. The M-IM did not affect phagocytosis in the primary macrophages. The M-IM-induced TNFα production was suppressed in the cells treated with a tolllike receptor 4 (TLR4) inhibitor called TAK-242. In conclusion, the M-IM modulates cytokine expression via TLR4 signaling and may play a role in the modulation of immune responses.

The aim of this study was to evaluate the chemical quenching system for residual ozone and to determine the operating condition for the quenching system. Hydrogen peroxide (H2O2) and sodium thiosulfate (Na2S2O3) were investigated as quenching reagents for ozone removal, and the tendency of each chemical was notably different. In the case of H2O2, the degradation rate of ozone was increased as the concentration of H2O2 increase, and temperature and pH value have a significant effect on the degradation rate of ozone. On the other hand, the degradation rate of ozone was not affected by the concentration of Na2S2O3, temperature and pH value, due to the high reactivity between the S2O3 2- and ozone. This study evaluates the decomposition mechanism of ozone by H2O2 and Na2S2O3 with consideration for the water quality and reaction time. Furthermore, the removal test for the quenching reagents, which can be remained after reaction with ozone, was conducted by GAC process.

Consumption of a high-fat diet increases some secondary bile acids (BAs) such as deoxycholic acid (DCA) in feces. DCA is derived from cholic acid (CA), a primary BA. We evaluated intestinal epithelial proliferation and BA metabolism in response to oral administration of cholic acid (CA) in rats to determine the influence of a CA diet on the responses of gut epithelia to γ-rays. WKAH/HkmSlc rats were divided into two dietary groups: control diet or CA-supplemented (2 g/kg diet) diet. Some of the rats from each group were irradiated with γ-rays, and epithelial cell proliferation in the colon was analyzed histochemically. Unirradiated CA-fed rats had high levels of DCA and CA in the sera, as well as the presence of taurocholic acid in their feces. Significant increases were observed in both epithelial proliferation and the number of epithelial cells in the colon of the CA-fed rats, and this effect was observed at 8 weeks after γ-ray exposure. Furthermore, extracts from both cecal contents and sera of the unirradiated CA-fed rats promoted proliferation of IEC-6 cells. These results indicate that BAs in enterohepatic circulation promote proliferation and survival of the intestinal epithelium after receiving DNA damage.

We investigated to determine whether a variety of acyl-homoserine lactones (AHLs) influences epithelial cell proliferation and mucosal permeability. 3-Oxo-C12-homoserine lactone (HSL) and 3-oxo-C14-HSL significantly suppressed IEC-6 cell proliferation. A significant increase in mucosal permeability was observed in isolated rat colon tissue exposed to C12-HSL, 3-oxo-C12-HSL, and 3-oxo-C14-HSL. These data indicate that AHLs suppress epithelial proliferation and disrupt barrier function in intestinal mucosa.

The signal molecule, 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), is similar to a mammalian hormone in bacteria. Although most studies have examined the effects of high 3-oxo-C12-HSL concentrations (>200 μM) on mammalian cellular functions because ~600 μM 3-oxo-C12-HSL can be secreted in biofilms of Pseudomonas aeruginosa grown in vitro, we previously showed that a low 3-oxo-C12-HSL concentration (30 μM) induces the apoptosis of undifferentiated Caco-2 cells through suppressing Akt activity. Here, we found that a low concentration of 3-oxo-C12-HSL-activated ERK1/2 in undifferentiated Caco-2 cells. Incubating cells with the ERK pathway inhibitor U0126 for 30 min alleviated the mucin 3 (MUC3) expression suppressed by 3-oxo-C12-HSL, and the upregulation of MUC3 expression induced by a 48-h incubation with U0126-reduced cell death. Thus, altered MUC3 expression caused by long-term attenuated ERK1/2 activity might correlate with the death of undifferentiated Caco-2 cells induced by 3-oxo-C12-HSL.

Three solid dispersions containing poorly water-soluble tacrolimus were prepared with hydroxypropyl-β-cyclodextrin (HP-β-CD) and dioctyl sulfosuccinate (DOSS) using a spray-drying technique via the solvent-evaporation method with a methylene chloride/ethanol mixture, the solvent-wetting method with ethanol and the surface-attached method with water, respectively. The solubility and dissolution of the drug in the three solid dispersions were evaluated compared to drug powder. Furthermore, their physicochemical properties were investigated using SEM, DSC and powder X-ray diffraction. The solubility and dissolution of the drug were significantly improved in the order of the tacrolimus-loaded solid dispersion prepared by: solvent-evaporation method > solvent-wetting method > surface-attached method. The solid dispersions prepared by solvent evaporation appeared as an aggregated form with the amorphous form. In particular, the solid dispersion prepared by the solvent-evaporation method improved solubility about 900-fold and dissolution of tacrolimus 15-fold because of its reduced particle size, increased surface area and close contact between the hydrophilic carrier and the drug. In the solvent-wetting method, the drug, which was changed to an amorphous form, was attached onto the surface of undissolved carriers. However, the solid dispersion prepared by the surface-attached method gave an unchanged crystalline form. In this solid dispersion, the carriers were attached to the surface of the undissolved drug, resulting in changing the drug from being hydrophobic to hydrophilic. As the crystal form of drug in this solid dispersion was not converted to the amorphous form unlike other solid dispersions, it gave relatively less solubility and dissolution of the drug than did the others. Thus, in the development of a solid-dispersion system containing poorly water-soluble drugs, the method of preparation plays an important role in the solubility and crystallinity of the drugs.

Desipramine belongs to a group of psychotropic compounds called tricyclic antidepressants that have similar chemical structures and share a variety of pharmacologic actions. They tend to be lipophilic and are found in high concentrations in the myocardium of treated patients.1 Actions responsible for most of their cardiovascular effects include anticholinergic properties, an ability to block norepinephrine reuptake and a type 1 antiarrhythmic action.1,2 A variety of cardiac dysrhythmias have been associated with tricyclic antidepressant usage and especially with overdosage.3 Sustained ventricular arrhythmias are an uncommon complication of nonfatal tricyclic antidepressant overdose4 and usually consist of polymorphous ventricular tachycardia (or ventricular fibrillation). In the present report, we describe a young person without apparent organic heart disease who ingested a large amount of desipramine and who presented with sustained monomorphic ventricular tachycardia which persisted over a 3-day period.