Effects of Astaxanthin Preparation Form on the Efficiency of Egg Yolk Pigmentation in Laying Hens.

This study investigated the effects of the preparation form of astaxanthin on egg yolk pigmentation and egg quality in laying hens. The following four astaxanthin sources were prepared in this study: (1) dried cell powder of Paracoccus carotinifaciens (Panaferd-AX), (2) fine cell powder of P. carotinifaciens (Panaferd-P), (3) astaxanthin oil suspension, and (4) water-soluble astaxanthin powder. These astaxanthin preparations were added to the basal diet at a final concentration of 2 mg/kg and fed to White Leghorn laying hens for 14 days. Although the administration of these astaxanthin preparations did not largely affect egg quality (i.e., egg weight, yolk weight, albumen height, and Haugh unit), feeding significantly improved astaxanthin concentration and yolk color fan score. When water-soluble astaxanthin powder was fed, the yolk astaxanthin concentration and color fan score were most improved, followed by Panaferd-P. These results indicated that astaxanthin pulverization and water solubilization significantly improved its bioavailability in laying hens. Furthermore, although diets rich in (all-E)-astaxanthin were fed to the hens, approximately 30% of astaxanthin was present as the Z-isomers in the egg yolk. These findings may contribute to improving not only the egg quality but the nutritional value of hen eggs.

Oral Supplementation with Z-Isomer-Rich Astaxanthin Inhibits Ultraviolet Light-Induced Skin Damage in Guinea Pigs.

The effect of oral supplementation with astaxanthin of different Z-isomer ratios on ultraviolet (UV) light-induced skin damage in guinea pigs was investigated. Astaxanthin with a high Z-isomer content was prepared from the all-E-isomer via thermal isomerization. Intact (all-E)-astaxanthin and the prepared Z-isomer-rich astaxanthin were suspended in soybean oil and fed to guinea pigs for three weeks. The UV-light irradiation was applied to the dorsal skin on the seventh day after the start of the test diet supplementation, and skin parameters, such as elasticity, transepidermal water loss (TEWL), and pigmentation (melanin and erythema values), were evaluated. The accumulation of astaxanthin in the dorsal skin was almost the same after consumption of the all-E-isomer-rich astaxanthin diet (E-AST-D; total Z-isomer ratio = 3.2%) and the Z-isomer-rich astaxanthin diet (Z-AST-D; total Z-isomer ratio = 84.4%); however, the total Z-isomer ratio of astaxanthin in the skin was higher in the case of the Z-AST-D supplementation. Both diets inhibited UV light-induced skin-damaging effects, such as the reduction in elasticity and the increase in TEWL level. Between E-AST-D and Z-AST-D, Z-AST-D showed better skin-protective ability against UV-light exposure than E-AST-D, which might be because of the greater UV-light-shielding ability of astaxanthin Z-isomers than the all-E-isomer. Furthermore, supplementation with Z-AST-D resulted in a greater reduction in skin pigmentation caused by astaxanthin accumulation compared to that of E-AST-D. This study indicates that dietary astaxanthin accumulates in the skin and appears to prevent UV light-induced skin damage, and the Z-isomers are more potent oral sunscreen agents than the all-E-isomer.

Extraction of Fucoxanthin Isomers from the Edible Brown Seaweed Undaria pinnatifida Using Supercritical CO2: Effects of Extraction Conditions on Isomerization and Recovery of Fucoxanthin.

Fucoxanthin, a characteristic carotenoid found in brown seaweeds, has been reported to exert beneficial biological activities, including antiobesity and anticancer activities Moreover, the Z-isomers of this compound potentially have greater bioavailability and biological activities than the naturally predominant all-E-isomer. Therefore, the consumption of Z-isomer-rich fucoxanthin through daily meals and dietary supplements may have beneficial effects. In this study, we aimed to investigate the effects of different extraction conditions on the Z-isomer ratio and recovery of fucoxanthin obtained from Undaria pinnatifida using supercritical CO2 (SC-CO2), particularly focusing on the high-temperature conditions that enhance thermal Z-isomerization. High-temperature SC-CO2 extraction at ≥ 120°C was found to enhance the thermal isomerization of fucoxanthin. For example, when the extraction was performed at 40, 80, 120, and 160°C and 30 MPa for 30 min with a co-solvent (ethanol), the total Z-isomer ratios were 11.7, 11.5, 18.7, and 26.5%, respectively. Furthermore, the high-temperature extraction significantly improved fucoxanthin recovery under high-pressure (≥ 30 MPa) conditions in the presence of the co-solvent. For example, when fucoxanthin was extracted at 40, 80, 120, and 160°C under the same conditions as above, the recoveries were 17.5, 20.6, 30.7, and 29.5%, respectively. Hence, the high-temperature SC-CO2 extraction of fucoxanthin from U. pinnatifida would not only enhance health benefits of fucoxanthin via the Z-isomerization but also improve the productivity. Moreover, the use of non-toxic CO2 and a low-toxicity organic solvent (ethanol) ensures that the final fucoxanthin product is safe for consumption. The Z-isomer-rich fucoxanthin obtained using this method is accordingly considered to have potential for use as a dietary supplement.

Application of E/Z-Isomerization Technology for Enhancing Processing Efficiency, Health-Promoting Effects, and Usability of Carotenoids: A Review and Future Perspectives.

Carotenoids are naturally occurring pigments whose presence in the diet is beneficial to human health. Moreover, they have a wide range of applications in the food, cosmetic, and animal feed industries. As carotenoids contain multiple conjugated double bonds in the molecule, a large number of geometric (E/Z, trans/cis) isomers are theoretically possible. In general, (all-E)-carotenoids are the most predominant geometric isomer in nature, and they have high crystallinity and low solubility in various mediums, resulting in their low processing efficiency and bioavailability. Technological developments for improving the processing efficiency and bioavailability of carotenoids utilizing the Z-isomerization have recently been gaining traction. Namely, Z-isomerization of carotenoids induces a significant change in their physicochemical properties (e.g., solubility and crystallinity), leading to improved processing efficiency and bioavailability as well as several biological activities. For the practical use of isomerization technology for carotenoids, the development of efficient isomerization methods and an acute understanding of the changes in biological activity are required. This review highlights the recent advancements in various conventional and unconventional methods for carotenoid isomerization, such as thermal treatment, light irradiation, microwave irradiation, and catalytic treatment, as well as environment-friendly isomerization methods. Current progress in the improvement of processing efficiency and biological activity utilizing isomerization technology and an application development of carotenoid Z-isomers for the feed industry are also described. In addition, future research challenges in the context of carotenoid isomerization have been elaborated upon.

Hungry Bone Syndrome After Living Donor Liver Transplant for Biliary Atresia.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

Evaluation and improvement of storage stability of astaxanthin isomers in oils and fats.

Astaxanthin Z-isomers potentially have greater bioavailability and biological activity than (all-E)-astaxanthin. However, the stability of the Z-isomers is lower than the all-E-isomer, which is a serious problem affecting its practical use. In this study, we investigated the impacts of different suspension media (oils and fats) and additives on astaxanthin isomer stability and identified suitable ones for astaxanthin stabilization. The evaluations showed that several vegetable oils and antioxidants significantly improved astaxanthin isomer stability, e.g., when soybean and sunflower oils were used as the suspension medium, astaxanthin isomers were hardly degraded; however the total Z-isomer ratio decreased from ~80% to ~50% during 6-week storage at 30 °C. Moreover, it was revealed that (9Z)-astaxanthin showed higher stability than the 13Z- and 15Z-isomers. Hence, to maintain astaxanthin concentration and the Z-isomer ratio over long periods, it is important to use suitable suspension mediums and antioxidants, and select a Z-isomerization method that increases (9Z)-astaxanthin ratio.

Astaxanthin Z-isomer-rich diets enhance egg yolk pigmentation in laying hens compared to that in all-E-isomer-rich diets.

The effects of feeding diets containing astaxanthin with different Z-isomer ratios to laying hens on egg qualities, such as astaxanthin concentration in egg yolk and yolk color, were investigated. As the astaxanthin source, a natural microorganism Paracoccus carotinifaciens was used. Astaxanthin with different Z-isomer ratios was prepared by thermal treatment with different conditions and then added to the basal diet at a final astaxanthin concentration of 8 mg/kg. We found that, as the Z-isomer ratios of astaxanthin in the diet increased, the astaxanthin concentration in egg yolk and the yolk color fan score also increased significantly. Importantly, feeding a 50.6% Z-isomer ratio diet increased astaxanthin concentration in egg yolk by approximately fivefold and the color fan score by approximately 2 compared to that in hens fed an all-E-isomer-rich diet. Moreover, we showed that feeding Z-isomer-rich astaxanthin to laying hens increased plasma astaxanthin concentration by more than five times in comparison to that in hens fed an all-E-isomer-rich diet. These results indicate that Z-isomers of astaxanthin have higher bioavailability than that of the all-E-isomer and thus they exhibit greater egg yolk-accumulation efficiency.

Synergistic Effects of Food Ingredients and Vegetable Oils on Thermal Isomerization of Lycopene.

Recent investigations have demonstrated that some food ingredients and vegetable oils, such as onion, garlic, and sesame oil, enhanced thermal Z-isomerization of (all-E)-lycopene in tomatoes. However, the synergistic effects of these ingredients and oils have not yet been investigated. This study aims at clarifying how the combined use of lycopene Z-isomerization-promoting food ingredients and vegetable oils impacts thermal Z-isomerization of (all-E)-lycopene in tomato puree. Apart from a few exceptions, when olive oil was used as a reaction medium, the combined use of garlic, cabbage, broccoli, shiitake mushroom, and makonbu improved the total Z-isomer ratio of lycopene after heating compared to the separate use of the tested ingredients. However, when onion was used together with the other ingredients, the Z-isomer ratio significantly decreased compared to its individual use. Moreover, when garlic, cabbage, broccoli, shiitake mushroom, and makonbu were used with sesame and mustard oils, that exhibit higher Z-isomerizationpromoting effect than that of olive oil, the lycopene Z-isomerization reaction was further enhanced. However, when onion was combined with these oils, the Z-isomer ratio decreased compared to that measured upon the combined use of onion with olive oil. Our results on these synergistic effects are not only important for the food and drink manufacturing industries but also for daily home cooking.

Production of (Z)-Lycopene-Rich Tomato Concentrate: A Natural Catalyst-Utilized and Oil-Based Study for Practical Applications.

Since lycopene Z-isomers exhibit greater bioavailability and biological activity than the naturally occurring all-E-isomer, efficient manufacturing methods for (Z)-lycopene-rich materials are urgently needed. Herein, a method was developed for Z-isomerization of (all-E)-lycopene in tomato oleoresin using heat treatment and a natural catalyst, viz. allyl isothiocyanate (AITC). For practical application of this isomerization technology, no organic solvents were used, and instead, oils and fats were used as the reaction medium. The Z-isomerization of (all-E)-lycopene was promoted by heating (>120 °C) even when oil and fat media were used. Allyl isothiocyanate enhanced thermal Z-isomerization and improved the (5Z)-lycopene content, which shows higher biological activity compared to the other Z-isomers. The thermal isomerization efficiency with AITC was further improved by using certain vegetable oils such as argan and olive oils. In addition, the storage stability of (Z)-lycopene-rich tomato concentrates dispersed in olive oil was evaluated. The total Z-isomer ratio and lycopene concentration decreased with longer storage periods, and it was revealed that (5Z)-lycopene showed excellent storage stability among the mono-Z-isomers.

Cardiac safety assessment with motion field imaging analysis of human iPS cell-derived cardiomyocytes is improved by an integrated evaluation with cardiac ion channel profiling.

We validated a motion field imaging (MFI) assay with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) as a model to assess multiple cardiac liabilities by comparing the guinea-pig Langendorff heart with hiPS-CMs using 4 reference compounds and 9 internal compounds. We investigated repolarization duration, beating rate (BR), conduction speed, contractility, and inhibitory profile of three cardiac ion channels: hERG, Cav1.2, and Nav1.5. For repolarization, the contraction-relaxation duration (CRDc) of hiPS-CMs was generally consistent with the QTc interval of Langendorff heart. However, 2 internal compounds shortened CRDc despite QTc prolongation in Langendorff heart. Cardiac ion channel profiling revealed that hiPS-CMs could not be used to detect QTc prolongation when the value of Cav1.2 IC50 / hERG IC50 for a compound was between 1 and 10, whereas hiPS-CMs showed responses largely consistent with Langendorff heart when Cav1.2 IC50 / hERG IC50 was below 1 or above 10. The accuracy of hiPS-CMs for the BR was not high, mainly because the BR of hiPS-CMs was increased by an inhibition of Cav1.2. The hiPS-CMs were highly sensitive to conduction speed and contractility, able to detect QRS widening caused by Nav1.5-inhibition, as well as decreased LVdP/dtmax caused by the inhibition of Cav1.2 and/or Nav1.5. In conclusion, the MFI assay with hiPS-CMs would be useful for evaluating multiple cardiac liabilities. The ion channel profile helps to interpret the results of MFI assay and correctly evaluate cardiac risks. Therefore, an integrated cardiac safety assessment with MFI and ion channel profiling is recommended.

Enhanced Z-isomerization of tomato lycopene through the optimal combination of food ingredients.

In tomatoes, most lycopene is present in the all-E-configuration and shows very low bioavailability, whereas the Z-isomers show higher bioavailability. Hence, for health reasons, it is expected that the ingestion of lycopene Z-isomers is preferable. Very recently, it was reported that onion and possibly garlic promoted thermal Z-isomerization of (all-E)-lycopene but there are no reports for other food ingredients. Here we show new food ingredients that enhance thermal Z-isomerization of lycopene in tomatoes and from the results, we guessed some causative components having the Z-isomerization promoting effect. A comprehensive investigation of food ingredients revealed that some vegetables (Allium sp., Brassica sp., and Raphanus sp.), shiitake mushroom (Lentinus edodes), and some edible seaweeds (Saccharina sp. and Ecklonia sp.) markedly promoted Z-isomerization of (all-E)-lycopene in tomato puree with heating at 80 °C for 1 h. Moreover, it was revealed that polysulfides, isothiocyanates, carbon disulfide, and iodine, which were commonly contained in the above food ingredients in considerable quantity, enhanced thermal Z-isomerization of (all-E)-lycopene. Our findings on the food ingredients and the food-derived catalysts having a carotenoid Z-isomerization promoting effect are important, not only for the food, drink, and dietary supplement manufacturing industries, but also for daily home cooking.

The thermal Z-isomerization-induced change in solubility and physical properties of (all-E)-lycopene.

The effect of Z-isomerization of (all-E)-lycopene on its solubility in organic solvents and physical properties was investigated. Lycopene samples containing different Z-isomer contents (23.8%, 46.9%, and 75.6% of total lycopene) were prepared from high-purity (all-E)-lycopene by thermal Z-isomerization in dichloromethane (CH2Cl2). As the Z-isomer content increased, the relative solubility of lycopene significantly improved. Although (all-E)-lycopene barely dissolved in ethanol (0.6 mg/L), the solubilities of lycopene containing 23.8%, 46.9%, and 75.6% Z-isomers were 484.5, 914.7, and 2401.7 mg/L, respectively. Furthermore, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses clearly indicated that (all-E)-lycopene was present in the crystal state, while Z-isomers of lycopene were present in amorphous states. A number of studies have suggested that Z-isomers of lycopene are better absorbed in the human body than the all-E-isomer. This may be due to the change in solubility and physical properties of lycopene by the Z-isomerization.

Safety assessment of a natural tomato oleoresin containing high amounts of Z-isomers of lycopene prepared with supercritical carbon dioxide.

BACKGROUND: Z-isomers of lycopene, which are abundantly present in processed tomato products, are more bioavailable than (all-E)-lycopene found predominantly in raw tomatoes. Despite extensive studies on the bioavailability and biological activities of Z-isomers of lycopene, detailed studies on their safety and toxicology are limited. RESULTS: The geno-, acute and subacute toxicities of tomato oleoresin that contained high amounts of lycopene Z-isomers (10.9% lycopene with 66.3% Z-isomer content) and had been prepared with supercritical carbon dioxide were investigated. The oleoresin was non-mutagenic in the Ames test with and without metabolic activation (S9 mix). The medial lethal dose (LD50 ) of the oleoresin in rats, as determined by a single-dose oral test, was more than 5000 mg kg body weight-1 (bw) [361 mg (Z)-lycopene kg bw-1 ]. In the 4-week repeated-dose oral toxicity test, rats were administered oleoresin at 4500 mg kg-1 day-1 [325 mg (Z)-lycopene kg bw-1 day-1 ]. There were no clinically significant changes with respect to vital signs, physical examination outcomes and laboratory test values during the test period. CONCLUSION: Based on our findings and as supported by its long history of consumption, tomato oleoresin that contains high amounts of Z-isomers of lycopene prepared with supercritical carbon dioxide can be considered as safe for human consumption. © 2016 Society of Chemical Industry.

Enhanced E/Z Isomerization of (All-E)-lycopene by Employing Iron(III) Chloride as a Catalyst.

UNLABELLED: Catalytic isomerization of (all-E)-lycopene to Z-isomers using iron(III) chloride was investigated and optimized under various conditions of solvents, concentrations of iron(III) chloride, and reaction temperatures. The total contents of Z-isomers converted were higher in the order of CH2 Cl2 (78.4%) > benzene (61.4%) > acetone (51.5%) > ethyl acetate (50.8%) at 20 °C for 3 h using 1.0 × 10(-3) mg/mL iron(III) chloride for 0.1 mg/mL (all-E)-lycopene. However, the decomposition of lycopene was markedly accelerated in CH2 Cl2 : the remaining lycopene after the reaction for 3 h and 12 h was only 79.4% and 47.5%, respectively. As the concentration of catalyst increased in acetone, the Z-isomerization ratio of lycopene increased to more than 80%, followed by rapid degradation of lycopene to undetectable levels using >4.0 × 10(-3) mg/mL iron(III) chloride with the above concentration of (all-E)-lycopene. Finally, greater isomerization (79.9%) was attained at 60 °C in acetone for 3 h in the presence of 1.0 × 10(-3) mg/mL iron(III) chloride, largely without decomposition of lycopene (remaining ratio of total amount of lycopene isomers after the reaction, 96.5%). As iron(III) chloride has found general use as a food additive for iron fortification and acetone is also widely used in the food field, this method can be applied to the food and beverage processing industry. PRACTICAL APPLICATION: The dietary intake of lycopene, a natural red pigment found in brightly colored vegetables and fruits such as tomatoes and watermelons, has been reported to lower the risk of some diseases, including cancer. Lycopene molecules occur naturally in a long and "straight" shape, but on the other hand lycopene molecules with "bent" forms are highly absorbed by living cells, and showed good antioxidant activity. This study has demonstrated the efficient production of the "bent" lycopene using ionic iron as an accelerator, which is often contained in nutritional supplements.

Spectral characterisation of Z-isomers of lycopene formed during heat treatment and solvent effects on the E/Z isomerisation process.

The geometric isomerisation of (all-E)-lycopene, purified from tomato paste, was investigated in various organic solvents. Isomerisation ratios to the Z-isomers of lycopene in CH2Cl2 and CHCl3 over 24h were calculated to be 19.7% and 11.4% at 4°C and 77.8% and 48.4% at 50°C, respectively. In CH2Br2, more than 60% was attained in the first several hours, independent of temperature. The predominant Z-isomers obtained thermally, (9Z)-lycopene and (13Z)-lycopene, were purified and their absorption maxima and molar extinction coefficients in hexane were determined for the first time. Absorption values at 460 nm were also measured for both Z-isomers along with (all-E)-lycopene to accurately evaluate their concentrations by HPLC analysis. This approach successfully revealed that (13Z)-lycopene formed predominantly in benzene or CHCl3 at 50°C; in contrast, the 5Z-isomer was preferentially obtained in CH2Cl2 or CH2Br2.

Preclinical QT safety assessment: cross-species comparisons and human translation from an industry consortium.

INTRODUCTION: In vivo models have been required to demonstrate relative cardiac safety, but model sensitivity has not been systematically investigated. Cross-species and human translation of repolarization delay, assessed as QT/QTc prolongation, has not been compared employing common methodologies across multiple species and sites. Therefore, the accurate translation of repolarization results within and between preclinical species, and to man, remains problematic. METHODS: Six pharmaceutical companies entered into an informal consortium designed to collect high-resolution telemetered data in multiple species (dog; n=34, cynomolgus; n=37, minipig; n=12, marmoset; n=14, guinea pig; n=5, and man; n=57). All animals received vehicle and varying doses of moxifloxacin (3-100 mg/kg, p.o.) with telemetered ECGs (≥500 Hz) obtained for 20-24h post-dose. Individual probabilistic QT-RR relationships were derived for each subject. The rate-correction efficacies of the individual (QTca) and generic correction formulae (Bazett, Fridericia, and Van de Water) were objectively assessed as the mean squared slopes of the QTc-RR relationships. Normalized moxifloxacin QTca responses (Veh Δ%/µM) were derived for 1h centered on the moxifloxacin Tmax. RESULTS: All QT-RR ranges demonstrated probabilistic uncertainty; slopes varied distinctly by species where dog and human exhibited the lowest QT rate-dependence, which was much steeper in the cynomolgus and guinea pig. Incorporating probabilistic uncertainty, the normalized QTca-moxifloxacin responses were similarly conserved across all species, including man. DISCUSSION: The current results provide the first unambiguous evidence that all preclinical in vivo repolarization assays, when accurately modeled and evaluated, yield results that are consistent with the conservation of moxifloxacin-induced QT prolongation across all common preclinical species. Furthermore, these outcomes are directly transferable across all species including man. The consortium results indicate that the implementation of standardized QTc data presentation, QTc reference cycle lengths, and rate-correction coefficients can markedly improve the concordance of preclinical and clinical outcomes in most preclinical species.

Characterization and thermal isomerization of (all-E)-lycopene.

A large amount of (all-E)-lycopene was successfully purified from tomato paste using an improved method that included a procedure to wash crystalline powder with acetone. The total yield of the pure (all-E) form was at least 30%. The melting point of (all-E)-lycopene was determined to be 176.35 °C by differential scanning calorimetry (DSC) measurements. Bathochromic shifts were observed in the absorption maxima of all solvents tested (at most a 36 nm shift for λ2 in carbon disulfide, as was observed in hexane) and were accompanied by absorbance decreases, namely, a hypochromic effect, showing a higher correlation between the position and the intensity of the main absorption bands. This bathochromic shift was dependent upon the polarizability of the solvent rather than its polarity. The structure of (all-E)-lycopene in CDCl3 and C6D6 was identified on the basis of one- and two-dimensional nuclear magnetic resonance (NMR) spectra, including (1)H and (13)C NMR, homonuclear correlation spectroscopy ((1)H-(1)H COSY), heteronuclear multiple-quantum coherence (HMQC), and heteronuclear multiple-bond connectivity (HMBC). The rate constants of the decrease in (all-E)-lycopene with hexane and benzene were calculated to be 3.19 × 10(-5) and 3.55 × 10(-5) s(-1), respectively. The equilibrium constants between (all-E) and (13Z) isomers were estimated to be 0.29 in hexane and 0.31 in benzene, respectively, from the point at which the amount of (13Z)-lycopene reached its maximum.

Culture of the hydrocarbon producing microalga Botryococcus braunii strain Showa: optimal CO2, salinity, temperature, and irradiance conditions.

Specific growth rates and hydrocarbon contents of Botryococcus braunii strain Showa were measured under a wide range of CO2, salinity, temperature, and irradiance conditions. The bubbling CO2 concentration of 0.2-5% and no addition of salinity were favorable conditions for growth. The strain cannot grow at 5°C and above 35°C under any irradiance levels. Maximum specific growth rate of 0.5 day(-1) (doubling time of 1.4 days), the highest value reported for B. braunii in the past studies, was observed at 30°C and 850 µmol photons m(-2) s(-1). Since hydrocarbon productivity, shown as the product of hydrocarbon content and specific growth rate, increased with the increasing specific growth rate, we conclude that more efficient hydrocarbon production by the mass culture of strain Showa can be achieved by maintaining higher specific growth rate based on the culture conditions presented in this study.

Inhibitory effects of a tryptamine derivative on ultraviolet radiation-induced apoptosis in MC3T3-E1 mouse osteoblasts.

MS-IPA1 is a new synthetic compound that is synthesized from tryptamine. Recently, our group demonstrated that SST-VED-I-1, which has a similar chemical structure to MS-IPA1, inhibits starvation-induced apoptosis in osteoblasts. However, the effects of MS-IPA1 on apoptosis in osteoblasts have not yet been examined. Therefore, this study examined the effects of this compound on apoptosis in osteoblasts. In this study, MC3T3-E1 mouse osteoblasts were used and apoptosis was induced by ultraviolet radiation (UV). We investigated the effect of MS-IPA1 on apoptosis by analyzing caspase3/7 activity, translocation of phosphatidylserine (PS), and mRNA expression levels of Bcl-2 and Bax. In addition, it was investigated whether MS-IPA1 affects cell proliferation and cell cycle progression. We found that MS-IPA1 had no effect on cell proliferation or cell cycle progression. However, MS-IPA1 suppressed UV-induced cell death in a dose-dependent manner, which was accompanied with the inhibition of caspase activation and translocation of PS. Furthermore, after UV exposure, Bcl-2 expression was increased in the MS-IPA1-treated cells as compared to that in the vehicle-treated cells. In contrast, Bax expression was decreased in the MS-IPA1-treated cell as compared to that in the vehicle-treated cells. These results suggest that MS-IPA1 has an inhibitory effect on apoptosis in osteoblasts through a Bcl-2 family-dependent signaling pathway.

Accurate detection of drug-induced delayed ventricular repolarization with a suitable correction formula in Langendorff guinea pig heart.

The aims of this study were to determine a suitable method to correct the ventricular repolarization period against the RR interval in isolated perfused Langendorff guinea pig heart and to clarify the reliability of this model using several drugs. QT and RR intervals from an electrocardiogram and the epicardial monophasic action potential duration (MAP(90)) were measured. Two drugs clinically known to be QT-prolonging (E-4031, moxifloxacin) and two known to be non-QT-prolonging (verapamil, zatebradine) were used for the study. To determine a method of correcting the ventricular repolarization period against RR interval, heart rates were slowed with 0.3 µM zatebradine, a specific bradycardiac agent, and then accelerated with atrial pacing to obtain a wide range of MAP(90)/RR relationships. An exponential rate-correction model elicited the most appropriate algorithm for the relationship among the four models tested. Based on linear regression analysis, the exponential showed superior dissociation of corrected MAP(90)s against RR intervals than generic Bazett's and Fridericia's formulae. E-4031 and moxifloxacin prolonged the corrected QT (QTc) intervals and MAP(90) under atrial pacing at a cycle length of 0.25 sec (MAP(90(pacing))) dose-dependently; verapamil and zatebradine failed to prolong them, indicating that the reliability of this model was excellent. MAP(90(pacing)) prolongation by moxifloxacin, the positive compound in the clinical "Thorough QT/QTc Study", was seen at around QTc-prolonging concentrations in clinic, suggesting that the sensitivity would be appropriate for QT evaluation. We therefore concluded that the isolated guinea pig heart model is sufficiently sensitive and useful for assessing the potential QT prolongation of drugs.