Insulin- and Lipopolysaccharide-Mediated Signaling in Adipose Tissue Macrophages Regulates Postprandial Glycemia through Akt-mTOR Activation.

The physiological role of immune cells in the regulation of postprandial glucose metabolism has not been fully elucidated. We have found that adipose tissue macrophages produce interleukin-10 (IL-10) upon feeding, which suppresses hepatic glucose production in cooperation with insulin. Both elevated insulin and gut-microbiome-derived lipopolysaccharide in response to feeding are required for IL-10 production via the Akt/mammalian target of rapamycin (mTOR) pathway. Indeed, myeloid-specific knockout of the insulin receptor or bone marrow transplantation of mutant TLR4 marrow cells results in increased expression of gluconeogenic genes and impaired glucose tolerance. Furthermore, myeloid-specific Akt1 and Akt2 knockout results in similar phenotypes that are rescued by additional knockout of TSC2, an inhibitor of mTOR. In obesity, IL-10 production is impaired due to insulin resistance in macrophages, whereas adenovirus-mediated expression of IL-10 ameliorates postprandial hyperglycemia. Thus, the orchestrated response of the endogenous hormone and gut environment to feeding is a key regulator of postprandial glycemia.

Pentafluorosulfanyl-substituted biaryl derivatives as MATE-type transporter inhibitors targeting drug-resistant bacteria.

Multidrug and toxin extrusion (MATE) inhibitors improve the antimicrobial susceptibility of drug-resistant bacteria by preventing the efflux of administered antibiotics. In this study, we optimized the chemical structure of a previously identified bacterial-selective MATE inhibitor 1 (EC50 > 30 µM) to improve its activity further. Compound 1 was divided into three fragments (aromatic part, linker part, and guanidine part), and each part was individually optimized. Compound 31 (EC50 = 1.8 µM), a novel pentafluorosulfanyl-containing molecule synthesized following optimized parts, showed antimicrobial activity against MATE-expressing strains at concentrations lower than conventional inhibitor 1 when co-administrated with norfloxacin. Furthermore, 31 was not cytotoxic at effective concentrations. This suggests that compound 31 can be a promising candidate for combating bacterial infections, particularly those resistant to conventional antibiotics by MATE expression.

The Feasibility of Using a Deep Learning-Based Model to Determine Cardiac Computed Tomographic Contrast Dose.

PURPOSE: This study aimed to predict contrast effects in cardiac computed tomography (CT) from CT localizer radiographs using a deep learning (DL) model and to compare the prediction performance of the DL model with that of conventional models based on patients' physical size. METHODS: This retrospective study included 473 (256 men and 217 women) cardiac CT scans between May 2014 and August 2017. We developed and evaluated DL models that predict milligrams of iodine per enhancement of the aorta from CT localizer radiographs. To assess the model performance, we calculated and compared Pearson correlation coefficient ( r ) between the actual iodine dose that was necessary to obtain a contrast effect of 1 HU (iodine dose per contrast effect [IDCE]) and IDCE predicted by DL, body weight, lean body weight, and body surface area of patients. RESULTS: The model was tested on 52 cases for the male group (mean [SD] age, 63.7 ± 11.4) and 44 cases for the female group (mean [SD] age, 69.8 ± 11.6). Correlation coefficients between the actual and predicted IDCE were 0.607 for the male group and 0.412 for the female group, which were higher than the correlation coefficients between the actual IDCE and body weight (0.539 for male, 0.290 for female), lean body weight (0.563 for male, 0.352 for female), and body surface area (0.587 for male, 0.349 for female). CONCLUSIONS: The performance for predicting contrast effects by analyzing CT localizer radiographs with the DL model was at least comparable with conventional methods using the patient's body size, notwithstanding that no additional measurements other than CT localizer radiographs were required.

A Novel Approach to Detecting Contrast Extravasation in Computed Tomography: Evaluating the Injection Pressure-to-Injection Rate Ratio.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of the injection pressure-to-injection rate (IPIR) ratio for the early detection of contrast extravasation at the venipuncture site during contrast-enhanced computed tomography. METHODS: We retrospectively enrolled 57,528 patients who underwent contrast-enhanced computed tomography examinations in a single hospital. The power injector recorded the contrast injection pressure at 0.25-second intervals. We constructed logistic regression models using the IPIR ratio as the independent variable and extravasation occurrence as the dependent variable (IPIR ratio models) at 1, 2, 3, 4, 5, and 6 seconds after the start of contrast administration. Univariate logistic regression models in which injection pressure is used as an independent variable (injection pressure models) were also constructed as a reference baseline. The performance of the models was evaluated with the area under the receiver operating characteristic curves. RESULTS: Of the 57,528 cases, 46,022 were assigned to the training group and 11,506 were assigned to the test group, which included 112 extravasation cases (0.24%) in the training group and 28 (0.24%) in the test group. The area under the receiver operating characteristic curves for the IPIR ratio models and injection pressure models were 0.555 versus 0.563 at t = 1 (P = 0.270), 0.712 versus 0.678 at t = 2 (P = 0.305), 0.758 versus 0.693 at t = 3 (P = 0.032), 0.776 versus 0.688 at t = 4 (P = 0.005), 0.810 versus 0.699 at t = 5 (P = 0.002), and 0.811 versus 0.706 at t = 6 (P = 0.002). CONCLUSIONS: The IPIR ratio models perform better in detecting contrast extravasation at 3 to 6 seconds after the start of contrast administration than injection pressure models.

Development of progressive multifocal leukoencephalopathy after cord blood transplantation in a patient with refractory angioimmunoblastic T-cell lymphoma.

A patient undergoing cord blood transplantation for refractory angioimmunoblastic T-cell lymphoma was subsequently managed with long-term immunosuppressants for chronic graft-versus-host disease (GVHD). On day 591 post-transplant, she exhibited disorientation and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain revealed two hyperintense foci in the white matter, suggestive of progressive multifocal leukoencephalopathy (PML). However, we did not include PML in the differential diagnosis at that time. Unfortunately, she developed progressive cognitive impairment, and repeated brain MRIs showed a progression in lesion size. She was still taking immunosuppressants to control her GVHD, therefore we suspected PML. The diagnosis of PML was confirmed through the detection of a John Cunningham (JC) virus in the cerebrospinal fluid on day 640 post-transplant. This report highlights the critical need to consider PML in differential diagnoses for post-allogeneic transplant patients, especially those who exhibit progressive neurological symptoms while on prolonged immunosuppressant therapy.

Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406.

Progression-free survival after R-High CHOP/CHASER/LEED with auto-PBSCT in untreated mantle cell lymphoma in JCOG0406 study. A continuous pattern of relapse was observed.

Deep learning-based reconstruction and 3D hybrid profile order technique for MRCP at 3T: evaluation of image quality and acquisition time.

OBJECTIVES: To evaluate the image quality of the 3D hybrid profile order technique and deep-learning-based reconstruction (DLR) for 3D magnetic resonance cholangiopancreatography (MRCP) within a single breath-hold (BH) at 3 T magnetic resonance imaging (MRI). METHODS: This retrospective study included 32 patients with biliary and pancreatic disorders. BH images were reconstructed with and without DLR. The signal-to-noise ratio (SNR), contrast, contrast-to-noise ratio (CNR) between the common bile duct (CBD) and periductal tissues, and full width at half maximum (FWHM) of CBD on 3D-MRCP were evaluated quantitatively. Two radiologists scored image noise, contrast, artifacts, blur, and overall image quality of the three image types using a 4-point scale. Quantitative and qualitative scores were compared using the Friedman test and post hoc Nemenyi test. RESULTS: The SNR and CNR were not significantly different when under respiratory gating- and BH-MRCP without DLR. However, they were significantly higher under BH with DLR than under respiratory gating (SNR, p = 0.013; CNR, p = 0.027). The contrast and FWHM of MRCP under BH with and without DLR were lower than those under respiratory gating (contrast, p < 0.001; FWHM, p = 0.015). Qualitative scores for noise, blur, and overall image quality were higher under BH with DLR than those under respiratory gating (blur, p = 0.003; overall, p = 0.008). CONCLUSIONS: The combination of the 3D hybrid profile order technique and DLR is useful for MRCP within a single BH and does not lead to the deterioration of image quality and space resolution at 3 T MRI. CLINICAL RELEVANCE STATEMENT: Considering its advantages, this sequence might become the standard protocol for MRCP in clinical practice, at least at 3.0 T. KEY POINTS: • The 3D hybrid profile order can achieve MRCP within a single breath-hold without a decrease in spatial resolution. • The DLR significantly improved the CNR and SNR of BH-MRCP. • The 3D hybrid profile order technique with DLR reduces the deterioration of image quality in MRCP within a single breath-hold.

Combination Use of Compressed Sensing and Deep Learning for Shoulder Magnetic Resonance Imaging With Various Sequences.

OBJECTIVE: For compressed sensing (CS) to become widely used in routine magnetic resonance imaging (MRI), it is essential to improve image quality. This study aimed to evaluate the usefulness of combining CS and deep learning-based reconstruction (DLR) for various sequences in shoulder MRI. METHODS: This retrospective study included 37 consecutive patients who underwent undersampled shoulder MRIs, including T1-weighted (T1WI), T2-weighted (T2WI), and fat-saturation T2-weighted (FS-T2WI) images. Images were reconstructed using the conventional wavelet-based denoising method (wavelet method) and a combination of wavelet and DLR-based denoising methods (hybrid-DLR method) for each sequence. The signal-to-noise ratio and contrast-to-noise ratio of the bone, muscle, and fat and the full width at half maximum of the shoulder joint were compared between the 2 image types. In addition, 2 board-certified radiologists scored the image noise, contrast, sharpness, artifacts, and overall image quality of the 2 image types on a 4-point scale. RESULTS: The signal-to-noise ratios and contrast-to-noise ratios of the bone, muscle, and fat in T1WI, T2WI, and FS-T2WI obtained from the hybrid-DLR method were significantly higher than those of the conventional wavelet method ( P < 0.001). However, there were no significant differences in the full width at half maximum of the shoulder joint in any of the sequences ( P > 0.05). Furthermore, in all sequences, the mean scores of the image noise, sharpness, artifacts, and overall image quality were significantly higher in the hybrid-DLR method than in the wavelet method ( P < 0.001), but there were no significant differences in contrast among the sequences ( P > 0.05). CONCLUSIONS: The DLR denoising method can improve the image quality of CS in T1-weighted images, T2-weighted images, and fat-saturation T2-weighted images of the shoulder compared with the wavelet denoising method alone.

Effects of dimension reduction of hyperspectral images in skin gross pathology.

BACKGROUND: Hyperspectral imaging (HSI) is an emerging modality for the gross pathology of the skin. Spectral signatures of HSI could discriminate malignant from benign tissue. Because of inherent redundancies in HSI and in order to facilitate the use of deep-learning models, dimension reduction is a common preprocessing step. The effects of dimension reduction choice, training scope, and number of retained dimensions have not been evaluated on skin HSI for segmentation tasks. MATERIALS AND METHODS: An in-house dataset of HSI signatures from pigmented skin lesions was prepared and labeled with histology. Eleven different dimension reduction methods were used as preprocessing for tumor margin detection with support vector machines. Cluster-wise principal component analysis (ClusterPCA), a new variant of PCA, was proposed. The scope of application for dimension reduction was also investigated. RESULTS: The components produced by ClusterPCA show good agreement with the expected optical properties of skin chromophores. Random forest importance performed best during classification. However, all methods suffered from low sensitivity and generalization. CONCLUSION: Investigation of more complex reduction and segmentation schemes with emphasis on the nature of HSI and optical properties of the skin is necessary. Insights on dimension reduction for skin tissue could facilitate the development of HSI-based systems for cancer margin detection at gross level.

[Efficacy of Bright Greenish-Yellow Fluorescence Sorting on Mycotoxin-Contaminated Nutmeg Selection and Characterization of Fungal Flora Related to Mycotoxin Production].

Spices have been known to be highly contaminated commodities with mycotoxins. The Codex Alimentarius reports that nutmeg is particularly contaminated with aflatoxins (AFs) and ochratoxin A (OTA). To eliminate contaminated commodities, visual sorting and bright greenish-yellow fluorescence (BGYF) sorting are used as low-cost technologies in production engineering. In Indonesia, nutmeg is mainly sorted by visual sorting and classified into three grades according to the Indonesian national standards, with importers further defining their own brand as imported products. In this study, we evaluate the efficacy of BGYF sorting as a further selection method to reduce AFs and OTA using the importer's own brand. Further, the level of these mycotoxins and the relationship between fungal flora and mycotoxin contamination were examined. These results showed that BGYF sorting effectively reduces AFs as well as OTA. In addition, BGYF-positive groups were infected by Aspergillus sections Flavi, Nigri, and Circumdati.

Fluorophenylalkyl-substituted cyanoguanidine derivatives as bacteria-selective MATE transporter inhibitors for the treatment of antibiotic-resistant infections.

Drug efflux pump inhibitors for the multidrug resistance protein HmrM, a member of the multidrug and toxin extrusion (MATE) family of transporters, were investigated to increase the drug susceptibility of multidrug-resistant bacteria and restore the antimicrobial effect of fluoroquinolones, such as norfloxacin. The lead inhibitor, prepared from the known hMATE1 inhibitor cimetidine, reduced the norfloxacin resistance of HmrM-expressing strains by 92% at non-cytotoxic concentrations in human cells, and multidrug resistance protein MdtK-expressing strains by 86%. These results indicated that the inhibitor is a lead candidate for the development of drugs with a novel mechanism of action against infections caused by multidrug-resistant bacteria that act synergistically with antimicrobial drugs.

Mite allergen avoidance decreases allergic symptoms in children in Ishinomaki city of Japan after natural disasters.

OBJECTIVE: We investigated the prevalence of asthma, rhinitis, and atopic dermatitis in children, evaluated the mite allergen levels in their bedding after the Great East Japan Earthquake, and assessed changes in allergic symptoms in children and their families after allergen avoidance practices. METHODS: We performed a survey for the International Study of Asthma and Allergies in Childhood (ISAAC) comprising 1109 children, aged 7-8 years, living in Ishinomaki, Japan. We collected responses from 464 children, and in 2016, measured the level of Dermatophagoides group 1 (Der 1) in the bedding of 202 of these children. The intervention group of children attended at least one allergen avoidance seminar. The levels of Der 1 in their bedding were measured, along with changes in allergic symptoms, in 17 children in 2017 and 14 children in 2018. The nonintervention group comprised children who did not attend an allergen avoidance seminar at any time. RESULTS: Of the 464 children who participated in the ISAAC, 50 (10.8%) reported having asthma, 179 (38.8%) allergic rhinitis, and 126 (27.3%) atopic dermatitis. The average level of Der 1 measured in the bedding of the 202 children in 2016 was 295.8 ng/m2. The levels of Der 1 in the intervention group-but not in the nonintervention group-significantly decreased in 2017 and 2018. The symptoms of asthma, allergic rhinitis, and atopic dermatitis in the children of intervention group and their families decreased after allergen avoidance practices. CONCLUSIONS: Allergen avoidance practices relieved allergic symptoms in school children after the Great East Japan Earthquake.

[Electrophysiological Effect of Citreoviridin on Human InducedPluripotent Stem Cell-derived Cardiomyocytes].

Citreoviridin (CTV) is a mycotoxin produced by various fungi, including Penicillium citreonigrum. One of the toxicities reportedly associated with CTV is neurotoxicity. CTV is also suspected to be associated with acute cardiac beriberi (also known as "Shoshin-kakke") and Keshan disease, which can have adverse effects on the heart, so the in vivo and in vitro toxicity of CTV on the heart or cardiomyocytes in experimental animal models have been reported. However, the toxicity of CTV for the human heart, especially its electrophysiological effect, remains poorly understood. Therefore, to investigate the electrophysiological effect of CTV on the human cardiomyocytes, we conducted a multi-electrode array (MEA) using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The MEA revealed that 30 µmol/L of CTV stopped the beating of hiPSC-CMs, and the field potential duration and first peak amplitude were shortened at 10 µmol/L. Before the hiPSC-CMs stopped beating, the length of the inter-spike interval varied two- to four-fold. These results demonstrated that CTV induced an electrophysiological disturbance on human cardiomyocytes. This is first paper to elucidate the electrophysiological effect of CTV on human heart directly and may aid in analyzing the risk associated with CTV to ensure food safety.

Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study.

A previous dose-finding study has suggested that romiplostim is effective in patients with refractory aplastic anaemia (AA) and 10 µg/kg once weekly was recommended as a starting dose. In this Phase II/III, multicentre, open-label study, romiplostim was administered subcutaneously at a fixed dose of 10 µg/kg once weekly for 4 weeks (weeks 1-4) followed by weekly doses (5, 10, 15 and 20 µg/kg) titrated by platelet response for up to 52 weeks (weeks 5-52). A total of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and thrombocytopenia (platelet count of ≤30 × 109 /l) were enrolled. The primary efficacy endpoint of the proportion of patients achieving any haematological (platelet, neutrophil and erythrocyte) response at week 27 was 84% [95% confidence interval (CI) 66-95%]. Trilineage response was 39% (95% CI 22-58%) at week 53. The most common treatment-related adverse events (AEs) were headache and muscle spasms (each 13%). All AEs were mild or moderate except for three patients with Grade 3 hepatic AEs; no AEs necessitated romiplostim discontinuation. Two patients developed cytogenetic abnormalities, of whom one returned to normal karyotype at last follow-up. High-dose romiplostim is effective and well tolerated in the treatment of patients with AA refractory to IST.

Association between Temporary Housing Habitation after the 2011 Japan Earthquake and Mite Allergen Sensitization and Asthma Development.

INTRODUCTION: We previously reported an increased prevalence of asthma in adults who lived in temporary housing after the 2011 Great East Japan Earthquake. The goal of the current study was to investigate changes in asthma prevalence and mite-specific immunoglobulin E (IgE) titers in temporary housing residents during 2014-2019. METHODS: By using the Global Initiative for Asthma guidelines, we diagnosed asthma in Ishinomaki city temporary housing residents aged 15 years or older. We then analyzed serum antigen-specific IgE levels to Dermatophagoides farinae (Der f), Dermatophagoides pteronyssinus (Der p), and Aspergillus fumigatus. RESULTS: The prevalence of asthma exceeded 20% across all age-groups throughout the study period. The proportion of study participants with a "positive" antigen-specific IgE titer (i.e., ≥0.35 IUA/mL) was higher in asthmatics than in nonasthmatics for Der f and Der p but not for Aspergillus fumigatus. Among residents ≥50 years old who were diagnosed with asthma, the percentage with a Der f-specific IgE titer ≥0.10 IUA/mL was higher than the proportion with ≥0.35 IUA/mL. Among study participants, asthma onset occurred before the earthquake, during residence in shelters or temporary housing, and (starting in 2016) after moving out of temporary housing. The Der p-specific IgE level was positively correlated with the duration of temporary housing (p < 0.05, r = 0.41) and inversely correlated with the time elapsed since moving out of temporary housing (p < 0.05, r = -0.35). CONCLUSION: Mite allergen sensitization was found in both asthmatic and nonasthmatic temporary housing residents after the 2011 Japan earthquake and tsunami; asthma developed even after subjects moved out of temporary housing.

The standardized method and clinical experience may improve the reliability of visually assessed capillary refill time.

OBJECTIVE: Reliability of capillary refill time (CRT) has been questionable. The purpose of this study was to examine that a standardized method and clinical experience would improve the reliability of CRT. METHODS: This was a cross-sectional study in the emergency department (ED). Health care providers (HCPs) performed CRT without instruments (method 1) to classify patients as having normal or abnormal (≤2/>2 s) CRT. An ED attending physician quantitatively measured CRT using a chronograph (standardized visual CRT, method 2). A video camera was mounted on top of the hand tool to obtain a digital recording. The videos were used to calculate CRT via image software (image CRT, method 3) as a criterion standard of methods. Additionally, 9 HCPs reviewed the videos in a separate setting in order to visually assess CRT (video CRT, method 4). RESULTS: We enrolled 30 patients in this study. Standardized visual CRT (method 2) identified 10 abnormal patients, while two patients were identified by CRT without instruments (method 1). There was no correlation (κ value, 0.00) between CRT without instruments (method 1) and image CRT (method 3), however the correlation between standardized visual CRT (method 2) and image CRT (method 3) was strong (r = 0.64, p < 0.01). Both intra-observer reliability and correlation coefficient with image CRT (method 3) was higher in video CRT (method 4) by more experienced clinicians. CONCLUSIONS: Visual assessment is variable but a standardized method such as using a chronograph and/or clinical experience may aid clinicians to improve the reliability of visually assessed CRT.

Importance of the Azole Moiety of Cimetidine Derivatives for the Inhibition of Human Multidrug and Toxin Extrusion Transporter 1 (hMATE1).

Herein, we describe the design and synthesis of cimetidine analogs, as well as their inhibitory activity toward the human multidrug and toxin extrusion transporter 1 (hMATE1), which is related to nephrotoxicity of drugs. Cimetidine is the histamine H2-receptor antagonist, but also inhibits hMATE1, which is known to cause renal impairment. We designed and synthesized cimetidine analogs to evaluate hMATE1 inhibitory activity to reveal whether the analogs could reduce the inhibition of hMATE1. The results showed that all analogs with an unsubstituted guanidino group exhibited hMATE1 inhibitory activity. On the other hand, there was a clear difference in the hMATE1 inhibitory activity for the other compounds. That is, compounds with a methylimidazole ring exhibited hMATE1 inhibition, while compounds with a phenyl ring did not. The results suggest that the ability to form hydrogen bonds at the azole moiety is strongly involved in the hMATE1 inhibition.

Evaluation of accuracy of capillary refill index with pneumatic fingertip compression.

Capillary refill time (CRT) is a method of measuring a patient's peripheral perfusion status through a visual assessment performed by a clinician. We developed a new method of measuring CRT using standard pulse oximetry sensor, which was designated capillary refill index (CRI). We evaluated the accuracy of CRI in comparison to CRT image analysis. Thirty healthy adult volunteers were recruited for a derivation study and 30 patients in the emergency department (ED) were for validation. Our high fidelity mechanical device compresses and releases the fingertip to measure changes in blood volume using infrared-light (940 nm). CRT was calculated by image analysis software using recorded fingertip videos. CRI and CRT were measured at: room temperature (ROOM TEMP), 15 °C cold water (COLD), and 38 °C warm water (REWARM). Intra-rater reliability, Bland-Altman plots, and correlation coefficients were used to evaluate the accuracy of the novel CRI method. CRI (4.9 [95% CI 4.5-5.3] s) and CRT (4.0 [3.6-4.3]) in the COLD group were higher than the ROOM TEMP and REWARM groups. High intra-rater reliability was observed in both measurements (0.97 [0.95-0.98] and 0.98 [0.97-0.99], respectively). The Bland-Altman plots suggested a systematic bias: CRI was consistently higher than CRT (difference: + 1.01 s). There was a strong correlation between CRI and CRT (r = 0.89, p < 0.001). ED patients had higher CRI (3.91 [5.05-2.75]) and CRT (2.21 [3.19-1.23]) than those of healthy volunteers at room temperature. The same difference and correlation patterns were verified in the ED setting. CRI was as reliable as CRT by image analysis. The values of CRI was approximately 1 s higher than CRT.

[In vivo and In vitro Mitigation Effects of Lactic Acid Bacteria Derived from Fresh Vegetables on Aflatoxins].

Aflatoxins (AFs) are known to be oncogenic mycotoxins. This study investigated the mitigation effects of lactic acid bacteria (LAB) isolated from four types of vegetable, cucumber, Chinese cabbage, Japanese radish and eggplant, which are used to make Japanese traditional fermented pickles, on AFs. Using aflatoxin M1 (AFM1) binding assay for screening, four representative strains were selected (one from each vegetable) from total 94 LAB strains, based on the highest binding ratio. The ranges of the binding ratio of these representative strains to aflatoxin B1 (AFB1), aflatoxin B2, aflatoxin G1, aflatoxin G2 and AFM1 were 57.5%-87.9% for the LAB strain derived from cucumber, 18.9%-43.9% for the LAB strain derived from Chinese cabbage, 26.4%-41.7% for the LAB strain derived from Japanese radish, and 15.0%-42.6% for the LAB strain derived from eggplant. The strains isolated from cucumber, Chinese cabbage, Japanese radish and eggplant were identified as Lactococcus lactis subsp. lactis, Weissella cibaria, Leuconostoc mesenteroides and Leu. mesenteroides, respectively. An in vitro binding assay of the four strains under acidic conditions showed that the number of living bacteria decreased, while the binding ratio increased in some strains, suggesting that the LAB maintained their capacity to bind aflatoxins even in an environment that imitated the stomach. An in vivo experiment using L. lactis subsp. lactis derived from cucumber revealed that the bacteria significantly inhibited the absorption of AFB1 into blood. These results showed that the LAB used for Japanese vegetable pickles was an effective binding agent of AFs and suggested that they might play a role in mitigating AF absorption.

[Analysis of Ciguatoxins in Variola louti Captured off the Ogasawara (Bonin) Islands].

Ciguatera poisoning (CP) is one of the most abundant seafood poisonings in the world. CP frequently occurred in the tropical and subtropical Indo-Pacific Ocean and the Caribbean Sea. In Japan, CP cases have been reported annually, from the subtropical regions, including Okinawa Prefecture and Amami Islands, Kagoshima Prefecture. The principal toxins, named ciguatoxins (CTXs), are bio-synthesized by benthic dinoflagellate of genera Gambierdiscus and Fukuyoa. They are bio-transferred herbivorous animals to carnivorous fishes via the food chain.The Ogasawara Islands comprise more than 30 islands, Mukojima Islands, Chichijima (Bonin) Islands, Hahajima Islands, Iwo Islands, Nishinoshima, Minamitorishima, and Okinotorishima, which locate in the tropical to subtropical regions. The Mukojima Islands, Chichijima Islands, and Hahajima Islands locate approximately the same latitude as Okinawa. The distance from Tokyo is approximately 1,000 km for Chichijima, 1,700 km for Okinotorishima (the southernmost tip of Japan), and 1,900 km for Minamitorishima (the easternmost tip of Japan). These islands exist in a wide range of waters, latitudes from 20°25' to 27°44' North and longitudes from 136°04' to 153° 59' East. We collected 65 specimens of a grouper, Variola louti, the most frequent species implicated in CP in Japan, from the waters around the Chichijima, Mukojima, and Hahajima islands. The fish flesh specimens were analyzed CTXs using the liquid chromatography-tandem mass spectrometer (LC-MS/MS). While the peak whose retention time is almost identical to that of CTX1B was detected in all specimens on our routine protocol, no 52-epi-54-deoxyCTX1B nor 54-deoxyCTX1B was detected. The peak retention time was quite different from that of CTX1B when re-analyzing by changing the analytical column. Thus, the CTXs in the specimens in the waters of these islands seemed to be undetectable levels.