Fetal 24-Segment Sphericity Index and Ventricular Fractional Shortening Between 12 and 20 Weeks of Gestation.

BACKGROUND: Although the fetal sphericity index (SI) and fractional shortening (FS) of 24 transverse segments have been previously reported after the 20th gestational week, there have been no reports during the first and early second trimester. OBJECTIVE: This study aimed to clarify the SI and FS of 24 transverse segments in normal fetuses before the 20th gestational week. METHODS: A total of 101 normal fetuses aged between 12 and 20 gestational weeks were examined. The displacement of the ventricular endocardium during the cardiac cycle was computed using speckle-tracking software (GE Healthcare, Milwaukee, WI). We analyzed the length of 24 end-diastolic lateral segments and the end-diastolic basal (seg1-6)- middle (Seg7-15)-apical (Seg16-24) distribution from the base to the apex of each ventricle, according to the method described by DeVore et al. The SI and FS were computed for each of the 24 segments by dividing the mid-basal-apical length by the transverse size. RESULTS: The SI for each segment was independent of the gestational age. The SI of the right ventricle was significantly lower than that of the left ventricle for segments 1-14, suggesting that the right ventricle was more spherical than the left ventricle in the basal segment only. The FS of the right ventricle was significantly lower than that of the left ventricle in segments 1 to 2 and 13 to 24. CONCLUSION: The morphology of the ventricles before 20 weeks of gestation differs from that between 20 and 40 weeks of gestation. This difference may be related to myocardial densification or performance.

Gut microbiota of one-and-a-half-year-old food-allergic and healthy children.

BACKGROUND: Intestinal bacteria may play a role in the development of food allergies. This study aimed to analyze and compare the gut microbiota of food-allergic children with that of healthy children of the same age. METHODS: Stool samples were collected from one-and-a-half-year-old food-allergic (FA group, n = 29) and healthy controls (HC group, n = 19). A questionnaire was provided to examine the children's birth, dietary, medical, and social histories. The gut microbiota was profiled by 16S rRNA sequencing. Differences in taxonomic composition were assessed using linear discriminant analysis effect size (LEfSe), and microbial functional profiles were predicted with Tax4Fun2. RESULTS: No significant difference in the alpha diversity index between the two groups; however, a negative correlation was observed between the Shannon diversity index and the relative abundance of Bacteroides. A significant difference was observed in beta diversity (permutational multivariate analysis of variance) in the bacterial composition between the FA and HC groups (P < 0.05). The FA group had a higher abundance of Escherichia and Anaeromassilibacillus and a lower abundance of Bacteroides, Oscillibacter, Ruminococcus, Hungateiclostridium and Anaerotaenia than the HC group (LEfSe: linear discriminant analysis score >2). The FA group showed a predicted increase in the expression levels of genes associated with intestinal pathogenicity compared with that in the HC group. CONCLUSIONS: The gut microbiota of food-allergic children has a higher abundance of bacteria involved in intestinal inflammation and a lower abundance of bacteria involved in immune tolerance than that of healthy children. This dysbiosis may also be associated with food allergies.

A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations.

Background: Allergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed. Objective: We sought to detect genetic variants associated with differences in immune responsiveness against allergen components. Methods: The participants of the present study were recruited from the Tokyo Children's Health, Illness, and Development study, and allergen component-specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16). Results: We performed GWAS on 564 participants of the Tokyo Children's Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10-8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10-8). Conclusions: Our data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.

Middle meatus microbiome in patients with eosinophilic chronic rhinosinusitis in a Japanese population.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease and is subdivided into eosinophilic and noneosinophilic forms. There are few reports investigating the nasal microbiome and its pathological functions in patients with CRS. OBJECTIVE: We sought to analyze factors contributing to variations of the nasal microbiome in CRS, and on the basis of these factors, to elucidate whether the bacterial metabolites were related to the pathogenesis. METHODS: Nasal swabs were collected, and the V3 to V4 variable region of the 16S ribosomal RNA gene was amplified and sequenced. Factors contributing to variations of the nasal microbiome in patients with CRS were compared. The most influential factor was whether CRS was eosinophilic, and we compared α- and ß-diversity, bacterial species, and predictive bacterial functions between the 2 patient groups. In addition, the metabolites of the key bacteria were extracted, and we evaluated the predicted bacterial functions in airway epithelial cells. RESULTS: In total, 110 patients with CRS and 33 control subjects were enrolled. On the basis of the factors of variation, it was found that patients with eosinophilic CRS (n = 65) had different microbiomes with weighted UniFrac ß-diversity and lower α-diversity compared with those with noneosinophilic CRS (n = 45). A higher abundance of Fusobacterium nucleatum and an increased LPS pathway were observed in patients with noneosinophilic CRS compared with those with eosinophilic CRS. In airway epithelial cells, LPS derived from F nucleatum suppressed the expression levels of ALOX15 induced by TH2 cytokines. CONCLUSIONS: The differences in the nasal microbiome may play a key role in the pathophysiology of CRS.

Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

OBJECTIVES: A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. METHODS: Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. RESULTS: Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. CONCLUSIONS: PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

Methylthioacetic acid, a derivative of aroma compounds from Cucumis melo var. conomon dose-dependently triggers differentiation and apoptosis of RCM-1 human colorectal cancer cells.

Methylthioacetic acid (MTA) is an acid-hydrolyzed derivative of a natural aroma compound, methylthioacetic acid ethyl ester isolated from Cucumis melo var. conomon (Katsura-uri, Japanese Picking Melon), and induces a villiform-like structure dome in RCM-1 human colorectal cancer cell culture. Thus far, the physiological and molecular properties of MTA-mediated dome formation remain unknown. Herein, MTA (not more than 2 mM) was demonstrated to differentiate the unorganized cell mass into the dome in RCM-1 cell culture by disclosing the correlation between dome formation and several intestinal differentiation markers such as alkaline phosphatase activity and the protein levels of dipeptidyl peptidase 4, villin, and Krüppel-like factor 4. Dome formation in RCM-1 cell culture was additively enhanced by the simultaneous administration of MTA and butyric acid (BA), suggesting that MTA directs the differentiation of RCM-1 cells, potentially through the same or similar pathway(s) shared with BA. Notably, a high dose of MTA (2 mM or more) elevated several apoptosis markers, such as DNA fragmentation, caspase-3/7 activity, and cleavage of poly(ADP-ribose) polymerase. Altogether, in addition to RCM-1 cell differentiation, MTA triggers apoptosis. These results indicate that MTA is a potential anticarcinogenic agent applicable in differentiation therapy and traditional chemotherapy against colorectal cancers.

Cat-Ear-Line: A Sonographic Sign of Cortical Development?

OBJECTIVES: Diagonal echogenic lines outside the lateral ventricle have often been observed in the anterior coronal planes of the normal fetal brain by neurosonography. We have observed abnormal shapes of these echogenic lines in cases of malformation of cortical development (MCD). We named the ultrasound finding "cat-ear-line" (CEL). This study aimed to examine how and when CEL develops in normal cases compared with MCD cases. METHODS: We retrospectively examined the fetal brain volume dataset acquired through transvaginal 3D neurosonography of 575 control cases and 39 MCD cases from 2014 to 2020. We defined CEL as the hyperechogenic continuous lines through subplate (SP) and intermediate zone (IZ), pre-CEL as the lines that existed only within the SP, and abnormal CEL as a mass-like or mosaic shadow-like structure that existed across the SP and IZ. All fetuses in the MCD group had some neurosonographic abnormalities and were ultimately diagnosed with MCD. RESULTS: The CEL was detected in 97.9% (369/377) of the control group from 19 to 30 weeks. The CEL visualization rate of the MCD group in the same period was 40.0% (14/35) which was significantly lower than that of the control group (P < .001). CONCLUSIONS: From this study, it appears that the CEL is an ultrasound finding observed at and beyond 19 weeks in a normally developing fetus. In some MCD cases, pre-CEL at and beyond 19 weeks or abnormal CEL was observed. Maldeveloped CEL at mid-trimester may help identify cases at-risk of subsequent MCD.

Classification of Southeast Asian mints (Mentha spp.) based on simple sequence repeat markers.

Mentha is a complex genus encompassing many species as a consequence of their interspecific hybridization and polyploidy. Southeast Asian mints have been poorly distinguished though they are widely used for culinary and medical purposes. In this study, we have analyzed Southeast Asian mints and known varieties as well as a related Lamiaceae species (Nepeta sp.) using simple sequence repeat (SSR) markers and leaf morphology. Two types of mints were clearly distinguished based on their venation pattern and leaf shape index. We developed 12 SSR markers that allowed good amplification in the Mentha and another Lamiaceae species. In the SSR-based phylogram, the Mentha lines could be delimited into groups I-VI. The Southeast Asian mints divided into groups I and II, and the phylogram separated most of the available species, with groups I and II containing the known species M. × cordifolia and M. arvensis, respectively. The separation of the two groups was supported by a population structure analysis. The SSR markers developed in this study enabled the simultaneous classification of mints and will help improve our understanding of the genetic composition of known mint varieties and as yet unclassified Southeast Asian mints.

Behavior and possible function of Arabidopsis BES1/BZR1 homolog 2 in brassinosteroid signaling.

Two key transcription factors (TFs) in brassinosteroid (BR) signaling BRASSINOSTEROID INSENSITIVE 1-EMS-SUPPRESSOR 1 (BES1) and BRASSINAZOLE RESISTANT 1 (BZR1), belong to a small family with four BES1/BZR1 homologs (BEH1-4). To date, in contrast to the wealth of knowledge regarding BES1 and BZR1, little is known about BEH1-4. Here, we show that BEH2 was expressed preferentially in the roots and leaf margins including serrations, which was quite different from another member BEH4, and that BRs downregulated BEH2 through a module containing GSK3-like kinases and BES1/BZR1 TFs, among which BES1, rather than BZR1, contributed to this process. In addition, BEH2 consistently existed in the nucleus, suggesting that its subcellular localization is not under BR-dependent nuclear-cytoplasmic shuttling control. Furthermore, gene ontology analysis on RNA-seq data indicated that BEH2 may be implicated in stress response and photosynthesis. These findings might assist in the future elucidation of the molecular mechanisms underlying BR signaling.

Oral antibiotics and a low-residue diet reduce the incidence of anastomotic leakage after left-sided colorectal surgery: a retrospective cohort study.

PURPOSE: Anastomotic leakage is a potential complication after colorectal surgery. We investigated the effects of oral antibiotics and a low-residue diet on the incidence of anastomotic leakage after left-sided colorectal surgery. METHODS: Outcomes were retrospectively compared between 64 patients who underwent mechanical bowel preparation alone (group A) and 183 patients who underwent mechanical bowel preparation with addition of oral kanamycin and metronidazole (group B) on the day before left-sided colorectal surgery. After surgery, patients in group A received a normal diet containing dietary fiber and those in group B received a low-residue diet. The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were rates of other postoperative complications, length of postoperative hospital stay, and laboratory data. RESULTS: Anastomotic leakage, surgical site infection, and diarrhea were less common in group B than in group A (4.9% vs 18.8%, 6.6% vs 23.4%, and 25.7% vs 43.8%, respectively). Postoperative C-reactive protein levels were significantly lower in group B. The median postoperative hospital stay was significantly shorter in group B than in group A (8 days vs 9 days, P = 0.010). Adaptive double least absolute shrinkage and selection operator regression revealed that use of preoperative oral antibiotics and a postoperative low-residue diet were associated with lower incidence of anastomotic leakage (odds ratio 0.163, 95% confidence interval 0.062-0.430; P < 0.001). CONCLUSION: Oral antibiotics and a low-residue diet reduced the incidence of anastomotic leakage and shortened the postoperative hospital stay by 1 day.

Clinical Validation of Fetal cfDNA Analysis Using Rolling-Circle-Replication and Imaging Technology in Osaka (CRITO Study).

BACKGROUND: Noninvasive prenatal genetic testing (NIPT) has been adopted as the first choice for aneuploidy screening. The purposes of this study were to investigate the accuracy of Vanadis® NIPT (hereafter CRITO-NIPT) in order to gain a deeper insight into the reasons for discrepancies, as well as to discuss the role of fetal ultrasound. METHODS: Between 2019 and 2020, CRITO-NIPT was performed in 1218 cases of patients who underwent CVS or amniocentesis after a detailed fetal ultrasound exam and genetic counseling. The CRITO-NIPT results were compared with the genetic results. In cases of test discrepancies, the placentae were collected for detailed genetic research, and the pre-procedure fetal ultrasound findings were referred to. RESULTS: The positive predictive value of T21, T18, and T13 was 93.55%, 88.46%, and 100%, respectively. In 90% of the of false positive (FP) cases, the placentae were examined. In 75% of the CRITO FP-T21 cases, placental mosaicism, or a demised twin's T21, were confirmed. There were complicated mosaic cases, including tetrasomy 21/trisomy7 and monosomy 21/trisomy21 cases. In one of three no-call cases, an intermediate deletion of chromosome 13 was detected. CONCLUSIONS: The CRITO study investigated the mechanism of false positives, and the detailed mechanisms in mosaic and no-call cases. There have hitherto been no reports that have provided insight by partitioning the placenta to compare the NIPT and invasive test results, nor that have provided detailed ultrasound findings in the cases of discordant results, revealing the demonstrated importance of, and necessity for, detailed ultrasonography. This article describes the potential of rolling-circle replication as a powerful biosensing platform, as well as the importance of examining the fetus in detail with ultrasound. However, we should remember that the potential applications raise ethical and social concerns that go beyond aneuploidy and its methodology.

[Questionnaire Survey of Pharmacy Students regarding Long-term In-hospital Practical Training: 8 Years of Changes].

In 2010, the in-hospital practical training period for pharmacy students was extended from 4 to 11 weeks. We have conducted questionnaire surveys of these students every year with the aim of reviewing the quality of training by conduction of surveys and evaluations. However, it was not clear whether reviewing based on the questionnaire results improved student satisfaction with the in-hospital practical training. Therefore, the aim of this study was to verify the validity of reviewing based on the questionnaire results by analyzing the data accumulated during the long-term practical training. A questionnaire survey was conducted of 333 5th-year students upon completion of practical training at Chiba University Hospital from 2010 to 2017. Students self-evaluated their attitude toward practical training on a 6-point scale and their satisfaction level for each component of the practical training on a 5-point scale. The students were also allowed to share their feelings about hospital pharmacy work. Repeated review of the training content can facilitate communication with patients, which was lacking at the beginning of the training period. Improved communication led to higher-quality pharmacy practice and increased student satisfaction. Meanwhile, changes to work procedures may reduce student satisfaction unless the training strategy is reviewed accordingly. Because the work of hospital pharmacists is constantly changing, it is considered that the content of the practical training should be revised accordingly through continuous conduction of surveys and evaluations, thereby enabling optimal practical training.

[Evaluation of the Usefulness of Postoperative Analgesic Solution Preparation by Pharmacists in the Surgical Department].

Pharmacists began preparing drug solutions intraoperatively for postoperative analgesia in the Department of Surgery at Chiba University Hospital from May 2014. To verify the usefulness of pharmacists preparing these drug solutions, we conducted a questionnaire survey among 51 anesthesiologists and received 44 responses (recovery rate 86.3%). Burden on the anesthesiologists was significantly reduced both temporally and mentally when the pharmacists prepared the drug solutions compared with when the anesthesiologists did (p<0.01). The anesthesiologists' degree of anxiety about sometimes having to prepare drug solutions alone without any confirmation was also significantly reduced when pharmacists prepared them (p<0.01), which implies the need for a double-check system. In addition, 88.6% of anesthesiologists said that they were reassured with preparations done by the pharmacists under a sterile environment using a clean bench. Overall, 88.6% of anesthesiologists responded that they were satisfied with the preparation of drug solutions by pharmacists. Based on the results of this survey, pharmacists' preparation of drug solutions for postoperative analgesia is considered to be useful in ensuring the quality and safety of medical care because it reduced anesthesiologists' work to prepare the drug solutions, allowing them to concentrate on anesthesia and related work, it established a double-check system between the two staff teams, and it was done under a sterile environment.

Usability assessment of drug-linking laboratory data listed on prescriptions for outpatients of chiba university hospital.

To evaluate the impact of pharmacotherapy on efficacy and safety by providing laboratory data information linked to medicines on outpatient prescriptions from the hospital to the community pharmacy. Beginning on October 28, 2014, standardized laboratory data and drug-linking laboratory data were included with outpatient prescriptions at our hospital. We have created a database of drug-linking laboratory data for all drugs that can be prescribed in Japan. We counted the number of prescription inquiries related to laboratory data from community pharmacies, including those leading to prescription changes. Before laboratory data were listed on outpatient prescriptions, 4 prescription inquiries from community pharmacies per year were related to laboratory data. After our hospital started to list laboratory data, this number rose to 643, 576, 563, and 847 in the first, second, third, and fourth year (P < .05). Of these, 132, 143, 152, and 224 inquiries resulted in prescription changes. Listing laboratory data on outpatient prescriptions avoided 153 contraindications and 84 exacerbations of adverse drug reactions in four years by a prescription inquiry that had never been done before. The efficacy and safety of pharmacotherapy can be improved by listing relevant laboratory data on outpatient prescriptions.

Neoantigen prediction in human breast cancer using RNA sequencing data.

Neoantigens have attracted attention as biomarkers or therapeutic targets. However, accurate prediction of neoantigens is still challenging, especially in terms of its accuracy and cost. Variant detection using RNA sequencing (RNA-seq) data has been reported to be a low-accuracy but cost-effective tool, but the feasibility of RNA-seq data for neoantigen prediction has not been fully examined. In the present study, we used whole-exome sequencing (WES) and RNA-seq data of tumor and matched normal samples from six breast cancer patients to evaluate the utility of RNA-seq data instead of WES data in variant calling to detect neoantigen candidates. Somatic variants were called in three protocols using: (i) tumor and normal WES data (DNA method, Dm); (ii) tumor and normal RNA-seq data (RNA method, Rm); and (iii) combination of tumor RNA-seq and normal WES data (Combination method, Cm). We found that the Rm had both high false-positive and high false-negative rates because this method depended greatly on the expression status of normal transcripts. When we compared the results of Dm with those of Cm, only 14% of the neoantigen candidates detected in Dm were identified in Cm, but the majority of the missed candidates lacked coverage or variant allele reads in the tumor RNA. In contrast, about 70% of the neoepitope candidates with higher expression and rich mutant transcripts could be detected in Cm. Our results showed that Cm could be an efficient and a cost-effective approach to predict highly expressed neoantigens in tumor samples.

Analysis of patients' request to switch from a generic drug to the original drug in external prescriptions.

BACKGROUND: Generic drugs are heavily promoted in Japan. The aim of this retrospective single-center study was to clarify whether the frequency and reason that patients request a switch from a generic drug to the original drug differ according to therapeutic category and dosage form. METHODS: This study was performed at Chiba University Hospital. Prescription inquiries about 121 generic drugs from community pharmacies over a 3-year period (from July 2014 to June 2017) were analyzed. RESULTS: Approximately 30% of the requests were related to the efficacy, safety, and comfort of the generic drug. The most cited motive was "patient's desire with no reason given" at 44.5%. According to multiple logistic regression analysis, therapeutic categories and dosage forms were associated with the requests. The median request frequency differed according to therapeutic category and dosage form. The frequency was highest for "agents affecting the central nervous system" and "tablets and capsules", respectively. Among the therapeutic categories, "agents affecting the central nervous system" had the highest median number of requests related to "decreased effectiveness"; "cardiovascular agents" had the highest median number of requests related to "physician's instruction"; and "agents for the epidermis" had the highest median number of requests related to "uncomfortable to use". Among dosage forms, the odds ratio for patients' original drug request for "liniment and patch" was about 1.5 times that for "tablets and capsules". "Liniment and patch" had the highest median frequency of requests related to "decreased effectiveness", "uncomfortable to use", and "patient's desire with no reason given". CONCLUSIONS: The request frequency and reason differed according to therapeutic category and dosage form. Pharmacists should advise each patient properly about the choice and switching of drug brands, taking into account the therapeutic category and dosage form, especially liniments and patches.

Chemical and molecular bases of dome formation in human colorectal cancer cells mediated by sulphur compounds from Cucumis melo var. conomon.

Colorectal cancer was the third most commonly diagnosed malignant tumor and the fourth leading cause of cancer deaths worldwide in 2012. A human colorectal cancer cell line, RCM-1, was established from a colon cancer tissue diagnosed as a well-differentiated rectum adenocarcinoma. RCM-1 cells spontaneously form 'domes' (formerly designated 'ducts') resembling villiform structures. Two sulphur-containing compounds from Cucumis melo var. conomon (Katsura-uri, or Japanese pickling melon), referred to as 3-methylthiopropionic acid ethyl ester (MTPE) and methylthioacetic acid ethyl ester (MTAE), can induce the differentiation of the unorganized cell mass of an RCM-1 human colorectal cancer cell culture into a dome. However, the underlying molecular mechanisms of such dome formation have not been previously reported. Here, we performed a structure-activity relationship analysis, which indicated that methylthioacetic acid (MTA) was the lowest molecular weight compound with the most potent dome-inducing activity among 37 MTPE and MTAE analogues, and the methylthio group was essential for this activity. According to our microarray analysis, MTA resulted in down-regulation of 537 genes and up-regulation of 117 genes. Furthermore, MTA caused down-regulation of many genes involved in cell-cycle control, with the cyclin E2 (CCNE2) and cell division cycle 25A (CDC25A) genes being the most significantly reduced. Pharmacological analysis showed that the administration of two cell-cycle inhibitors for inactivating CDC25A phosphatase (NSC95397) and the cyclin E2/cyclin-dependent kinase 2 complex (purvalanol A) increased the dome number independently of MTA. Altogether, our results indicate that MTA is the minimum unit required to induce dome formation, with the down-regulation of CDC25A and possibly CCNE2 being important steps in this process.

Investigation on the Epoxidation of Piperitenone, and Structure-activity Relationships of Piperitenone Oxide for Differentiation-inducing Activity.

Piperitenone oxide, a major chemical constituent of the essential oil of spearmint, Mentha spicata, induces differentiation in human colon cancer RCM-1 cells. In this study, piperitenone oxide and trans-piperitenone dioxide were prepared as racemic forms by epoxidation of piperitenone. The relative configuration between two epoxides in piperitenone dioxide was determined to be trans by 1H NMR analysis and nuclear Overhauser effect spectroscopy (NOESY) in conjunction with density functional theory (DFT) calculations. Optical resolution of (±)-piperitenone oxide by high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) afforded both enantiomers with over 98% enantiomeric excess (ee). Evaluation of the differentiation-inducing activity of the synthetic compounds revealed that the epoxide at C-1 and C-6 in piperitenone oxide is important for the activity, and (+)-piperitenone oxide has stronger activity than (-)-piperitenone oxide. The results obtained in this study provide new information on the application of piperitenone oxide and spearmint for differentiation-inducing therapy. Furthermore, natural piperitenone oxide was isolated from M. spicata. The enantiomeric excess of the isolated natural piperitenone oxide was 66% ee. Epoxidation of piperitenone with hydrogen peroxide proceeded in a phosphate buffer under weak basic conditions to give (±)-piperitenone oxide. These results suggest that the nonenzymatic epoxidation of piperitenone, which causes a decrease in the enantiomeric excess of natural piperitenone oxide, is accompanied by an enzymatic epoxidation in the biosynthesis of piperitenone oxide.

Contribution of Katsura-uri (Japan's Heirloom Pickling Melon, Cucumis melo var. conomon) at the Completely Ripe Stage to Diabetes Control.

The fruit of Katsura-uri (Japan's heirloom pickling melon, Cucumis melo var. conomon) possesses a fruity aroma and moderate sweetness. The fruit juice has potential to minimize human postprandial blood glucose levels. This study provides information regarding the health benefits of Katsura-uri and its utility in treating diabetes. The study methodology involved measuring the color and firmness of Katsura-uri fruit at five ripening stages, and quantitation of the aroma substances, proximate composition, and sugars. Significant changes were detected in the color, firmness, and level of aroma substances with ripening of Katsura-uri fruit, albeit with no major changes in proximate composition, with the exception of dietary fiber, and sugars. To determine the effects of Katsura-uri juice, the blood glucose levels of ten diabetic volunteers aged 46-75 y were monitored after its consumption, and compared with after consumption of muskmelon juice equivalent to the total weight of Katsura-uri juice. The blood glucose area under the curve level was significantly lower after consumption of Katsura-uri juice (16±5 h • mg/dL) than after consumption of muskmelon juice (55±17 h • mg/dL; p<0.05). The level of the glucose spike was also significantly lower after consumption of Katsura-uri juice (22±5 mg/dL) than after consumption of muskmelon juice (64±6 mg/dL; p<0.05). The completely ripe Katsura-uri fruit provides the best results for diabetic subjects, which is the first case of fruits sweetened with the addition of zero-calorie sweeteners.