Time-Dependent Inhibition of CYP1A2 by Stiripentol and Structurally Related Methylenedioxyphenyl Compounds via Metabolic Intermediate Complex Formation.

Stiripentol (STP), an antiepileptic agent, causes drug-drug interactions by inhibiting cytochrome P450 (P450) enzymes. STP contains a methylenedioxyphenyl (MDP) group, which could form inhibitory metabolic intermediate complexes (MICs) with P450. The present study examined the possible time-dependent inhibition of CYP1A2 via MIC formation by STP and structurally related MDP compounds such as isosafrole. Time-dependent inhibition was observed in human liver microsomes for CYP1A2, but not CYP3A4. Spectral analysis of the liver microsomes from CYP1A-induced rats incubated with STP and NADPH revealed a Soret peak at approximately 455 nm, which was largely eliminated by potassium ferricyanide. Similar spectra were obtained for all the other MDP compounds, albeit in varying amounts. Thus, the extent of time-dependent CYP1A2 inhibition and MIC formation were in good agreement. In addition, the dissociation of MIC by potassium ferricyanide partially attenuated the impairment of CYP1A2 activity, suggesting that MIC is involved in the time-dependent inhibition of CYP1A2 by STP. In conclusion, STP, like other MDP compounds, caused time-dependent CYP1A2 inhibition via MIC formation, and this may be involved in drug-drug interactions associated with the clinical use of STP. Significance Statement The present study found that stiripentol, an antiepileptic agent, caused a time-dependent inhibition of CYP1A2. Stiripentol like isosafrole has a methylenedioxyphenyl group and generated MI complexes with CYP1A2. This is a new case of the time-dependent CYP inhibition by a methylenedioxyphenyl containing drug via MI complex formation.

Effect of radiofrequency heating of vacuum-packed nitrite-free sausage on quality properties and microorganism inactivation.

The effect of radiofrequency (RF) heating technology at 27 MHz and 8 kW on the quality properties of vacuum-packed nitrite-free sausages was investigated. One of the several advantages of RF heating technology is the use of less time compared to retort heating. RF heating at 125 °C for a holding time of 2 min and retort heating at 121 °C for 7 min reduced Bacillus subtilis to 7 log cfu/g. In addition, the textural properties of the RF-heated sausages were better than those of retort-heated samples. Furthermore, the growth of B. subtilis and general live bacteria at 25 °C were not detected after 42 days of shelf life in the sausages that underwent RF heating at 125 °C with a holding time of 2 min.

The effect of radio-frequency heating on vacuum-packed saury (Cololabis saira) in water.

We characterized vacuum-packed whole saury (Cololabis saira) treated using radio-frequency (RF) heating and compared it with that treated using conventional retort heating. RF heating is electrical heating based on dielectric heating. In this study, the effect of RF heating on softening and collagen in backbone was analyzed. RF heating heated the center of fish faster than water. The backbone was softened to a chewable level, and the heating time was shortened to one-third. The amount of crude protein and collagen in backbone decreased with decreasing elasticity, although that heated using RF (131°C) still contained a higher amount than conventional heating. However, ß and γ collagen, and then α1 and α2 collagen chain in backbone disappeared with heating; therefore, collagen was degraded to collagen peptide. Results confirmed that RF heating provided wholly eatable fish containing low-molecular collagen peptide in a short heating time.

Microbial denitrification dominates nitrate losses from forest ecosystems.

Denitrification removes fixed nitrogen (N) from the biosphere, thereby restricting the availability of this key limiting nutrient for terrestrial plant productivity. This microbially driven process has been exceedingly difficult to measure, however, given the large background of nitrogen gas (N2) in the atmosphere and vexing scaling issues associated with heterogeneous soil systems. Here, we use natural abundance of N and oxygen isotopes in nitrate (NO3 (-)) to examine dentrification rates across six forest sites in southern China and central Japan, which span temperate to tropical climates, as well as various stand ages and N deposition regimes. Our multiple stable isotope approach across soil to watershed scales shows that traditional techniques underestimate terrestrial denitrification fluxes by up to 98%, with annual losses of 5.6-30.1 kg of N per hectare via this gaseous pathway. These N export fluxes are up to sixfold higher than NO3 (-) leaching, pointing to widespread dominance of denitrification in removing NO3 (-) from forest ecosystems across a range of conditions. Further, we report that the loss of NO3 (-) to denitrification decreased in comparison to leaching pathways in sites with the highest rates of anthropogenic N deposition.

Development of a radio frequency heating system for sterilization of vacuum-packed fish in water.

We developed equipment that quickly and uniformly heats packed whole fish in circulating tap water using radio frequency (RF) heating. Four vacuumed plastic-packed Pacific sauries in tap water were set in a radial arrangement between coaxial cylindrical electrodes in a closed vessel. For sterilization testing, Bacillus subtilis spores added in the center of the sauries were counted after treatment. For quality assurance, meat color and backbone hardness were measured after treatment. The temperature at the center of the sauries was increased up to 130 °C for 19 min using 9 kW RF heating, and up to 119 °C for 45 min using conventional heating (CH) at 120 °C. B. subtilis spores were decreased by five logarithmic orders using RF heating and by four logarithmic orders using CH. The RF-treated meat was brighter than the CH-treated meat, and the RF-treated backbone was softer than CH-treated one.

[Serotonin syndrome in a patient with small cell lung cancer].

The patient was a 67-year-old male who had been treated for several years with 150 mg fluvoxamine maleate due to depression. He visited our hospital with primary symptoms of swelling of the right upper extremity and dyspnea in August, XXXX. As a result of examinations, he was diagnosed with stage IIIB extended small cell lung cancer(T4N3M0). One course of carboplatin/etoposide(CBDCA/VP-16)therapy was started on October 1. Since the tumor size was reduced, thoracic effusion disappeared, and superior vena cava syndrome was alleviated, the therapy was changed to cisplatin/irinotecan (CDDP/CPT-11)on October 23, and the 3rd course was initiated on November 22. Anxiety and tremor appeared on the 4th day of the 3rd course and because they were exacerbated, and myoclonus appeared, a diagnosis of serotonin syndrome was made on the 38th day, and the administration of fluvoxamine maleate was discontinued. The symptoms were alleviated after the discontinuation, and the 4th course could be implemented. In this patient, serotonin syndrome was considered to have been induced by serotonin secretion promoted by the CDDP administration, and by serotonin in the brain increasing abnormally due to the SSRI.

Spread of a chromosomal cefixime-resistant penA gene among different Neisseria gonorrhoeae lineages.

In Neisseria gonorrhoeae, the mosaic type of penA, which encodes penicillin-binding protein 2 (PBP 2), is associated with reduced susceptibility to oral cephalosporins. To investigate the relatedness of N. gonorrhoeae clinical isolates with reduced susceptibility, we sequenced the penA genes of 32 isolates. Five different amino acid sequence types of PBP 2 were identified, but all seemed to be derivatives of pattern X of PBP 2 (PBP 2-X). However, multilocus sequence typing of the isolates showed that the isolates belonged to six different sequence types. As PBP 2-X was identified in three different sequence types, horizontal transfer of the penA allele encoding PBP2-X was suggested. We demonstrated that the penA gene could be transferred from an isolate with reduced susceptibility to a sensitive isolate by natural transformation. Comparison of the sequence of the penA-flanking regions of 12 transformants with those of the donor and the recipient suggested that at least a 4-kb DNA segment, including the penA gene, was transferred. During horizontal transfer, some of the penA alleles also acquired variations due to point mutations and genetic exchange within the allele. Our results provide evidence that the capacity for natural transformation in N. gonorrhoeae plays a role in the spread of chromosomal antibiotic resistance genes and the generation of diversity in such genes.

Spray technology applications of xanthan gum-based edible coatings for fresh-cut lotus root (Nelumbo nucifera).

In this study, the effect of spraying method as an application technique for xanthan gum-based edible coatings was investigated, based on its barrier and microbial properties on fresh-cut lotus root. Xanthan gum solutions (0.1%, 0.3%, and 0.5%) were prepared and incorporated with 2% (w/w) citric acid as an anti-browning agent and 1% (w/w) glycerol as plasticizer. The coatings were then sprayed using a pilot spray system to 5 mm-thick slices of fresh-cut lotus root for 20 s, packed in polyethylene bags, stored for 16 d at 5 °C and analyzed for color, pH, morphology and microbial counts. It was found that spray-coated fresh-cut lotus root samples had significant reduction in the total color changes as compared to non-coated samples. The experimental results suggested that the spray coating treatments were effective in decreasing the enzymatic browning of fresh-cut lotus root during storage which could potentially increase its shelf-life in the market. In addition, we have also found that the xanthan gum-based spray coated treatments were also effective against inhibiting the growth of Bacillus subtilis during 24 h of incubation which were indicated by the lower microbial counts recorded as compared to non-coated fresh-cut lotus root samples. In this part of the work, the author highlighted the spray coating technique of xanthan gum-based edible coatings as a promising strategy in improving the storage stability of fresh-cut lotus root during post-harvest storage. Overall, the application of edible coatings is a promising strategy in extending the shelf life of fresh-cut lotus root. In the future, the author aims to widen the scope of the application of these coatings to other agricultural products which are prone to degradation during storage in the market.

[Storage and transport of isolated M. tuberculosis at public and private health institutions in Japan].

PURPOSE: To obtain basic data about the present practices on storage and transport of isolated M. tuberculosis at public and private health institutions in Japan. METHOD: Survey forms regarding the practices on storage and transport of isolated M. tuberculosis were distributed and collected by post-mail in January 2007 to 76 local public health institutions, 145 public health centres, and 150 public or private hospitals. The questionnaire was adopted from the guidelines proposed by the Ministry of Health, Labour, and Welfare in 2006 on storage and transport of isolated M. tuberculosis. RESULTS: The respondents of the survey were as follows: 96.1% (73/76) from local public health institutions, 93.8% (136/145) from public health centres, and 73.3% (110/150) from hospitals. In general, local public health institutions conformed well to the proposed standards, however public health centres and hospitals were not compliant to some standards. SUMMARY: Based on the survey conducted on the practice of storage and transport of isolated M. tuberculosis, certain discrepancy was found among public health centres and hospitals.

[Antibiotic susceptibility of Neisseria meningitidis from healthy and diseased persons in Japan].

We examined the susceptibilities of 100 Neisseria meningitidis strains isolated between 1990 and 2004 to 12 antimicrobial agents, finding the MIC50 to be 0.031 microg/mL and that of MIC90 of benzylpenicillin (PCG), a type of penicillin, to be 0.063 microg/mL. Two strains showed intermediate resistance (MIC of 0.125-0.25 microg/mL). Two strains of the same origin also showed intermediate resistance (0.25-1 microg/mL) to ampicillin (ABPC). For cephems, MIC50 and MIC90 of cefotaxime (CTX) were both 0.004 microg/mL, while the MICs of ceftriaxone (CTRX) were all 0.004 microg/mL, showing the strongest antibacterial spectrum. The three carbapenems surveyed meropenem (MEPM), panipenem (PAPM), and imipenem (IPM) also had a strong antibacterial spectrum in ascending order, with the MIC50 and MIC90 of MEPM, which was lowest, being 0.008 microg/mL and 0.016 microg/mL. Some 97% of MICs for ciprofloxacin (CPFX) were 0.004 microg/mL but 3 strains showed resistance (0.125 microg/mL). No difference was seen between MICs of N. meningitidis strains originated from meningitis patients, patients other than meningitis, and healthy carriers. No difference was seen in MICs by serogroup (A, B, C, Y, W135 and NG).

Association between plasma oxidized low-density lipoprotein and diabetic nephropathy.

To investigate the association of oxidized low-density lipoprotein (ox-LDL) with the development of diabetic nephropathy, plasma levels of ox-LDL were measured in 70 patients with type 2 diabetes mellitus. A sandwich enzyme-linked immunoadsorbent assay (ELISA) using the mouse monoclonal antibody FOH1a/DLH3, which specifically recognizes oxidized phosphatidylcholine, and a horseradish peroxidase (HRP)-labeled goat anti-human apolipoprotein B IgG was used to measure ox-LDL levels. The mean age of the patients was 57.0+/-1 3.4 years, and the mean duration of diabetes was 13.4+/-8.5 years. Plasma ox-LDL levels were similar in patients with normoalbuminuria (13.7+/-3.9 U/ml), patients with microalbuminuria (12.8+/-3.9 U/ml), and normal controls (12.5+/-4.2 U/ml). However, the plasma ox-LDL level in patients with macroalbuminuria (16.8+/-7.5 U/ml) was significantly higher than those in the other groups (P<0.05). Hemoglobin A1c (HbA1c) levels were similar in diabetic patients with normoalbuminuria (8.2+/-2.2%), microalbuminuria (7.8+/-1.3%), or macroalbuminuria (7.2+/-1.4%). There was no significant correlation between the ox-LDL level and the HbA1c level. The significantly elevated plasma ox-LDL levels in patients with macroalbuminuria suggest that ox-LDL may play an important role in the progression of diabetic nephropathy.

Estimation of food portion sizes frequently consumed by children 3-6 years old in Japan.

No study has documented Japanese children's food portion sizes. Since this information is essential to establish valid measurement tools and effective education methods for dietary intake, we measured them using one-day, semi-weighed diet records (DRs) for 489 Japanese children aged 3-6 y. Each food's frequency of appearance on the DRs was counted. If a child consumed a certain food more than once per day, an average weight for that food was calculated and used in the portion size calculation as that child's representative value. In total, 67 food items were consumed by twenty or more children. We calculated the mean, standard deviation, median, minimum, and maximum portion size values for these food items. In addition to these 67 items, Chinese noodles and water were included in the analysis. The most frequently consumed food was well-milled rice (mean portion size for rice=79 g), which was consumed by 350 children, followed by soy sauce (4 g), eggs (26 g), and carrots (9 g). Among the five most frequently consumed foods, portion sizes of rice and pork but not milk, eggs, or carrots significantly increased with age, height, and weight. In multivariate linear regression analysis, however, the significant relationships between rice portion size and age were not observed. Regarding pork, only the relationship with height was significant. A sex difference was detected in the rice and milk portion sizes. Most of portion sizes observed here were apparently smaller than those reported among United Kingdom children. This study provides important basic information for the implementation of quantitative nutritional research and educational efforts for Japanese preschool children.