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Sesame (Sesamum indicum L.) plant contains large amounts of acteoside, a typical phenylethanoid glycoside (PhG) that exhibits various pharmacological activities. Although there is increasing interest in the biosynthesis of PhGs for improving their production, the pathway remains to be clarified. In this study, we established sesame-cultured cells and performed transcriptome analysis of methyl jasmonate (MeJA)-treated cultured cells to identify enzyme genes responsible for glucosylation and acylation in acteoside biosynthesis. Among the genes annotated as UDP-sugar dependent glycosyltransferase (UGT) and acyltransferase (AT), 34 genes and one gene, respectively, were up-regulated by MeJA in accordance with acteoside accumulation. Based on phylogenetic analysis, five UGT genes (SiUGT1–5) and one AT gene (SiAT1) were selected as candidate genes involved in acteoside biosynthesis. Additionally, two AT genes (SiAT2–3) were selected based on sequence identity. Enzyme assays using recombinant SiUGT proteins revealed that SiUGT1, named UGT85AF10, had the highest glucosyltransferase activity among the five candidates against hydroxytyrosol to produce hydroxytyrosol 1-O-glucoside. SiUGT1 also exhibited glucosyltransferase activity against tyrosol to produce salidroside (tyrosol 1-O-glucoside). SiUGT2, named UGT85AF11, had similar activity against hydroxytyrosol and tyrosol. Enzyme assay using the recombinant SiATs indicated that SiAT1 and SiAT2 had activity transferring the caffeoyl group to hydroxytyrosol 1-O-glucoside and salidroside (tyrosol 1-O-glucoside) but not to decaffeoylacteoside. The caffeoyl group was attached mainly at the 4-positon of glucose of hydroxytyrosol 1-O-glucoside, followed by attachment at the 6-position and the 3-position of glucose. Based on our results, we propose an acteoside biosynthetic pathway induced by MeJA treatment in sesame.

The Japanese Pharmacopoeia (JP) is an official normative publication that is referred to, for establishing the authenticity and properties and maintaining the quality of pharmaceutics in Japan. Partial amendments are periodically made to these guidelines to keep up with the progress of science and technology, and the international harmonization is revised every 5 years. Thus, "Internationalization of the JP" is one of the more important issues to address for the revision of the JP. For example, the incorporation of the test methods that have been used in other pharmacopeias, such as the United States Pharmacopeia (USP) and the European Pharmacopoeia (EP), into the JP is a useful approach. In light of this, we have recently reported changes in test methods in the 17th JP, "Establishment of a quantitative test method for clonidine hydrochloride from using a potentiometric titration method to using HPLC". As a part of our ongoing research to change test methods for internationalization, we selected lorazepam. Lorazepam is analyzed using a potentiometric titration method as listed in the 17th JP; however, both the USP and EP use HPLC for quantitative analysis of this drug. In this study, we synthesized the related impurities of lorazepam listed in the USP and the EP and determined their purities using quantitative NMR. The separation conditions of these compounds, including lorazepam, were examined using HPLC and simultaneous analyses were performed. In addition, lorazepam extracted from the tablets was analyzed using conditions similar to those used for the analysis of the related impurities.

Mogroside V is one of the characteristic and effective components of luohanguo extract, a food additive used as a sweetener in Japan as per Japan's Standards and Specifications for Food Additives (JSFA; 9th ed.). JSFA stipulates that the quantitative determination for mogroside V content in luohanguo extract applies HPLC using analytical standard mogroside V. However, no mogroside V reagents with proven purities are commercially available. Therefore the current JSFA determination method is not particularly suited for daily quality control operations involving luohanguo extract. In this study, we applied an alternative quantitative method using a single reference with relative molar sensitivity (RMS). It was possible to calculate the accurate RMS by an offline combination of 1H-quantitative NMR spectroscopy (1H-qNMR) and an HPLC/variable-wavelength detector (VWD). Using the RMS of mogroside V to a commercial certified reference material grade caffeine, the mogroside V contents in luohanguo extracts could be determined using HPLC/VWD without analytical standard mogroside V. There was no significant difference between the mogroside V contents in luohanguo extracts determined using the method employing single-reference caffeine with the RMS and using the JSFA method. The absolute calibration curve for the latter was prepared using an analytical standard mogroside V whose purity was determined by 1H-qNMR. These results demonstrate that our proposed method using a single reference with RMS is suitable for quantitative determination of mogroside V in luohanguo extract and can be used as an alternative method to the current assay method in JSFA.

Traumatic anterior cerebral artery (ACA) aneurysms are extremely rare. Traumatic anterior ACA aneurysms are thought to develop when the ACA at the pericallosal segment travel adjacent to immobile falx cerebri. As the majority of aneurysms are pseudoaneurysms, direct neck clipping is usually not possible, and it is often necessary to carry out direct or endovascular trapping in conjunction with proficient bypass techniques. The authors describe the first reported case of a traumatic ACA pseudoaneurysm resulting from avulsion of the falcine branch of an azygos ACA. In this case, the lacerated aneurysm wall was successfully sutured, without the need for a bypass. Neurosurgeons should be aware that avulsion of the falcine branch arising from the ACA can occur, and that this may cause a traumatic aneurysm on the distal ACA. Furthermore, direct suturing of a lacerated arterial wall should be considered a treatment option for this type of traumatic intracranial aneurysm.

Summary: Background: Inguinal hernia is one of the most common surgical diseases, and surgical residents perform inguinal hernia repairs during pediatric surgery rotation. The aims of this study were to examine the clinical outcomes of pediatric inguinal herniorrhaphy performed by surgical residents and to assess the suitability for surgical training. Methods: We extracted data on elective unilateral inguinal hernia repairs performed in children between 2014 and 2018. All eligible cases were divided into surgical resident and attending surgeon groups according to the operator. We reviewed medical records retrospectively and compared some clinical indicators between the 2 groups. Results: Of 294 eligible cases, 163 were performed by 37 surgical residents and 131 were performed by 4 attending surgeons. The median operative times in the resident and attending surgeon groups were 30 and 19 min, respectively. Operative time was statistically longer in the resident group (p

The localization of acteoside and its precursors in different organs of sesame plant (Sesamum indicum L.), including roots, stems (epidermis, cortex, and stele), leaves (blades and petioles), flower petals, and seeds (immature and mature) was investigated. The highest acteoside content was found in leaf blades (12.3% dry weight), followed by in petioles (3.1%) and petals (2.7%) and at a trace levels or not detected in other organs. In contrast, the known precursors of acteoside, cinnamate, p-coumarate, caffeate, tyramine, tyrosol, salidroside, l-3,4-dihydroxyphenylalanine, dopamine, and hydroxytyrosol were not detected in any organs, even by multiple-reaction monitoring analysis by liquid chromatography–electrospray ionization tandem mass spectrometry, despite acteoside being present at high levels in the leaves. The leaves stained with diphenylborinic acid 2-aminoethyl ester (DPBA), producing the acteoside–DPBA complex that was detected by fluorescence at an excitation wavelength of 365 nm, showed accumu...

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants. Daikenchuto, a Japanese herbal drug, has several effects on the digestive system, so we investigated its preventive effects in a rat model of NEC. NEC was induced in newborn rats via asphyxia (100% N2 for 90 s; every 4 h) + LPS (4 mg/kg/day [administered orally on days 0 and 1]). The effects of Daikenchuto were evaluated in four groups (control: 0 g/kg/day, I: 0.3 g/kg/day, II: 0.6 g/kg/day, and III: 1.0 g/kg/day). Daikenchuto was administered into the stomach through a microcatheter. The incidence and severity of NEC were pathologically assessed using the NEC grade in accordance with Dovorak’s previous report. Cell positivity for inflammatory cytokine (IL-6) was also evaluated. Daikenchuto reduced the incidence of NEC in control, Groups I, II, and III to 68.7, 30.0, 30.7, and 13.3%, respectively. High-dose Daikenchuto significantly improved the incidence of NEC, and the rate of IL-6 positive cells in group III was significantly lower than in the control group (p = 0.04). We evaluated the effect of Daikenchuto against NEC and found that it reduced the incidence rate of NEC due to a decrease in the IL-6 production.

Hirschsprung’s disease (HSCR) is a congenital disorder of the enteric nervous system characterized by the absence of ganglion cells in the Auerbach’s and Meissner’s plexuses. Although about 7% of cases are hereditary, the causal mutations have not been completely characterized. We encountered a novel family with inherited HSCR and screened them for causal mutations. A Japanese family of five female patients and six unaffected individuals was subjected to a whole-exome analysis with a next-generation sequencer. After exome sequencing and the annotation of mutations, we identified co-segregated mutations with sequential filtering steps via a standard protocol. Eight mutations were identified: two on chromosome 10 and six on chromosome 11. We used pathogenicity prediction tools such as Genomic Evolutionary Rate Profiling, SIFT, and PolyPhen2 to predict the impact of mutations on the protein activity. S922Y, a novel mutation of RET, was identified as a likely causal mutation. In addition, a mutation of rs2435357T, known as enhancer of RET located in intron 1 of RET, was detected in this family. The coexistence of RET mutations in both the exon (S922Y) and intron1 (rs2435357T) indicated a risk of HSCR in this family.

Summary Background Allied disorders of Hirschsprung's disease (ADHD) have been proposed to be the concept of the functional obstruction of the intestine with the presence of ganglion cells in the terminal rectum. They are classified into two categories based on pathology: (1) abnormal ganglia, including immaturity of ganglia, hypoganglionosis (HG), and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), segmental dilatation (SD), internal anal sphincter achalasia (IASA), and chronic idiopathic intestinal pseudo-obstruction (CIIP). Some of these show poor prognosis, therefore, the establishment of criteria and appropriate treatment strategies is required. Methods The questionnaires were sent to the 161 major institutes of pediatric surgery or gastroenterology in Japan, in order to collect the cases of ADHD during 10 years from 2001 and 2010. Results In total, 355 cases were collected. They included 28 immaturity of ganglia, 130 HG (121 congenital, 9 acquired), 18 intestinal neuronal dysplasia, 33 MMIHS, 43 SD, three IASA, and 100 CIIP. Of the 95 institutes, 69 (72.6%) had their own criteria for ADHD. Criteria were based on clinical symptoms and signs, and conventional pathological examinations. Prognosis was poor in congenital HG, MMIHS, and CIIP, while the others showed good survival rates. Conclusion Almost all Japanese cases of ADHD in the past 10 years were collected. Congenital HG and CIIP showed relatively high incidence, whereas acquired HG and IASA were extremely rare in Japan. The criteria of each disorder were also collected and summarized. Prognosis was poor in congenital HG, MMIHS, and CIIP.

Hirschsprung’s disease shows transit disorder of intestinal content, delayed meconium excretion, abdominal distention, bilious vomiting, constipation, and intestinal dilatation (megacolon) at proximal side, resulting from aperistalsis and lack of the recto-anal reflex caused by aganglionosis of the distal segment. In the pediatric surgery field, the disease has been widely recognized, the condition has been elucidated, and the therapy has been developed. In these clinical and research settings, there is a disease group which has symptoms and laboratory findings similar to those of Hirschsprung’s disease despite the presence of ganglion cells in the rectum. It has been called “allied Hirschsprung’s disease” in Japan. However, the disease concept and diseases included in the group have been changed over time, and a consensus is not yet established among specialists.

We recently reported that Pseudomonas sp. ITH-SA-1 can transform the lignin-derived aromatic compound syringaldehyde (SYAL) into nonaromatic polymeric substances with fluorescent activity (NAPSFA). NAPSFA are particularly rare organic substances that fluoresce despite the absence of aromatic rings. In this study, we developed a simple method for producing NAPSFA using a nonbiological process. Incubation of the SYAL metabolite 3-O-methyl gallate (3-MGA) produced by Pseudomonas sp. ITH-SA-1 with Marine Broth (MB) or Luria–Bertani broth (LB) produced fluorescence even in the absence of bacteria, suggesting that fluorescent substances were produced from 3-MGA by a nonbiological process. 3-MGA reacted with tryptone and peptone, which are the primary nitrogen and phosphate sources in MB and LB, to produce the fluorescent substances. The fluorescent substances produced by the reaction of 3-MGA with tryptone exhibited excitation and emission peaks at 370 and 505 nm, respectively, which are nearly identical to tho...

Agnus Castus Fruit is defined in the European Pharmacopoeia as the dried ripe fruit of Vitex agnus-castus. In Europe it is used as a medicine targeting premenstrual syndrome and climacteric disorder. In Japan, Agnus Castus Fruit is becoming popular as a raw material for over-the-counter drugs and health food products, though its congenic species, Vitex rotundifolia and Vitex trifolia, have been used as Shrub Chaste Tree Fruit in traditional medicines. Therefore, it is important to discriminate these Vitex plants from the viewpoint of regulatory science. Here we tried to identify putative marker compounds that distinguish between Agnus Castus Fruit and Shrub Chaste Tree Fruit. We analyzed extracts of each crude drug by liquid chromatography-mass spectrometry, and performed differential analysis by comparison of each chromatogram to find one or more peaks characteristic of Agnus Castus Fruit. A peak was isolated and identified as an equilibrium mixture of new compounds named chastol (1) and epichastol (1a). The planar structures of 1 and 1a were determined spectroscopically. Their relative configurations were revealed by nuclear Overhauser effect spectroscopy and differential nuclear Overhauser effect-NMR data. Since avoiding contamination from closely related species is needed for the quality control of natural pharmaceuticals, this information will be valuable to establish a method for the quality control of both, Agnus Castus Fruit and Shrub Chaste Tree Fruit products.

Shrub Chaste Tree Fruit (SCTF) is defined as the fruits of Vitex rotundifolia L. f. and V. trifolia L. and has been used as a component of some traditional Japanese medicines (Kampo formulations). Agnus Castus Fruit (ACF) is defined as the dried ripe fruits of V. agnus-castus L.; it is used in traditional European medicines, but is becoming popular in Japan as both an over-the-counter drug and as an ingredient in health foods for treating premenstrual syndrome (PMS). To ensure the efficacy and safety of both SCTF and ACF products, it is important to precisely authenticate their botanical origins and to clearly distinguish between SCTF and ACF. Therefore, we tried to identify SCTF-specific marker compounds based on LC/MS metabolic analysis. The multivariate analysis of LC/MS data from SCTF and ACF samples furnished candidate marker compounds of SCTF. An SCTF-specific marker was isolated from SCTF crude drugs and identified as 3-O-trans-feruloyl tormentic acid on the basis of spectroscopic data from NMR and MS. Since avoiding contamination from closely related species is a significant requirement for pharmaceuticals of natural origin, this information will be valuable for the quality control of both SCTF and ACF products from the viewpoint of regulatory science.

In this paper, we discuss the first two cases who underwent colostomy closure using ICG fluorescence system (Stryker, PINPOINT System®). Case 1 11-months-old female with 21 trisomy and anorectal malformation (rectal atresia without fistula). She had sigmoid loop colostomy in neonatal period and Posterior Sagittal Anorectoplasty (PSARP) in 9 months of life. During the colostomy closure, ICG was intravenously administered to evaluate blood flow of anastomotic site. Twenty-two hours after operation, she had the first defecation which was positive for ICG fluorescence. Case 2 16-months old male with postoperative state of tracheoesophageal fistula and rectovestivular fistula. He had transverse loop colostomy in neonatal period and PSARP in 12 months of life. During the colostomy closure, ICG was intravenously administered to evaluate blood flow of anastomotic site. Twenty-five hours after operation, he had the first defecation which was negative for ICG fluorescence. Forty hours after operation, he had ICG-positive defecation. There were no postoperative complications for both of patients. ICG fluorescence system has two merits for pediatric colostomy closure evaluation of anastomotic blood flow and postoperative bowel function.

Acquired isolated hypoganglionosis (A-IH) is a late-onset intestinal pseudo-obstruction disorder and shows different pathophysiological findings from congenital isolated hypoganglionosis (C-IH). In this study, we retrospectively examined five cases of A-IH and investigated the features of A-IH. Five cases of A-IH were extracted from a nationwide retrospective cohort study in 10 years, from which totally 355 cases of Allied Disorders of Hirschsprung’s Disease (ADHD) were collected. Ages of onset were between 13 and 17 years in three cases, and 4 years and 4 months in ones. Initial symptoms were abdominal distension and/or chronic constipation in 4 cases, whereas one exhibited intestinal perforation. Affected lesions varied from case to case, extending various length of intestinal tracts. All cases underwent multiple operations (average: 4.6 times), such as enterostomy, resection of dilated intestines, and/or pull-through. Pathological findings showed the decreased numbers of ganglion cells and degeneration of ganglion cells, whereas the size of the plexus was normal. Currently, all cases were alive and almost all eat regular food without requiring parenteral feeding. A-IH is rare, but distinct entity characterized by different clinical courses and pathological findings from those of C-IH. The outcome is considered to be favorable after a resection of affected intestine.

We examined bacteria capable of transforming lignin-derived compounds into industrially or economically valuable substances from the seawater after the Great East Japan Earthquake-caused tsunami. Pseudomonas sp. ITH-SA-1 produced water-soluble fluorescent substances from the lignin-derived aromatic, syringaldehyde (SYAL). They: are polymeric substances derived from 3-O-methyl gallate produced through transformation of SYAL via syringate; are not known compounds reported previously; have excitation/emission peaks at 365/498 nm, respectively; and have an average molecular weight of 7.2 kDa. Despite the fact that aromatic structure generally plays an important role in the planarity and rigidity of organic fluorescent substance, the spectroscopic analyses revealed that aromatic rings were not detected in the molecules. Their activity is particularly rare and the biotransforming capabilities will contribute to the development of new basic techniques for the effective utilization of lignin.

Background Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. Methods These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. Results We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. Conclusions Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Of all brain metastases, the most common primary lesion is derived from the lung. These types of metastases enlarge aggressively with unfavorable prognoses. We report the case of a 75-year-old male patient who had a history of pulmonary resection for Stage IA non-small cell lung cancer(NSCLC), and received chemotherapy. One year after NSCLC surgery, he experienced a cardiogenic cerebral infarction, and anticoagulant therapy was initiated. Mass lesions with hemorrhage were detected bilaterally in the frontal lobes through magnetic resonance imaging three years after the NSCLC surgery. The lesions slowly enlarged during follow-up. However, there were no clinical symptoms. There was no finding indicating a local recurrence or metastasis through positron emission tomography(PET). Two and a half years after the detection of the lesion, left hemiplegia was observed. Massive hemorrhage from the right frontal lobe lesion was observed on computed tomography(CT). Craniotomy and evacuation of the hematoma were performed. The histopathological findings showed adenocarcinoma and the diagnosis was brain metastasis of the lung cancer. This case reveals brain metastasis of lung cancer that progressed without extracranial metastases for three years. The brain tumor enlarged, accompanied by hemorrhage, extremely slowly without any symptoms. It was difficult to differentiate between metastasis and cavernous hemangioma, considering the extremely slow progress and image analyses. Of the reported prognostic factors associated with postoperative brain metastasis from surgically resected NSCLC, three factors were applicable to this case:adenocarcinoma, a small number of brain metastases, and the absence of extracranial metastases at the diagnosis of brain metastasis. We should consider the possibility of a metastatic brain tumor secondary to lung cancer even long after thoracic surgery.

Background The use of nuclear medicine for the management of malignant tumor, such as radioguided surgery and sentinel lymph node biopsy (SLNB), has been widely accepted in the adult practice. However, there are very few studies to apply those techniques for pediatric diseases. The aim of this study was to investigate the feasibility of application of nuclear medicine in surgery for neuroblastoma (NB) or rhabdomyosarcoma (RMS) in children. Methods Radioguided surgery using 123I-metaiodobenzylguanidine was performed on six children with NB. SLNB using technetium-labeled tin or sulfur colloid was performed on two children with perineal RMS. Histological evaluation of resected specimens was performed to determine the accuracy of intraoperative detection and SLNB. All patients were evaluated for overall survival and complications. Results Intraoperative tumor localization using hand-held gamma probe was helpful in 85.7% of NB patients. Sensitivity and specificity of this technique were 81.8% and 93.3%, respectively. There were no postoperative complications, and four out of five patients with high-risk NB experienced disease-free survival (median follow up, 57 months). Sentinel lymph nodes were easily detected in patients with perineal RMS, and histological assessment revealed complete consistency with regional lymph node status. Conclusions Nuclear medicine may have a potential application in the use of less invasive surgery for advanced NB or perineal RMS, the two most challenging pediatric malignancies.

Steroidal estrogens are potent endocrine-disrupting chemicals that enter natural waters through the discharge of treated and raw sewage. Because estrogens are detrimental to aquatic organisms at sub-nanogram per liter concentrations, many studies have measured so-called "free" estrogen concentrations in wastewater effluents, rivers, and lakes. Other forms of estrogens are also of potential concern because conjugated estrogens can be easily converted to potent free estrogens by bacteria in wastewater treatment plants and receiving waters and halogenated estrogens are likely produced during wastewater disinfection. However, to the best of our knowledge, no studies have concurrently characterized free, conjugated, and halogenated estrogens. We have developed a method that is capable of simultaneously quantifying free, conjugated, and halogenated estrogens in treated wastewater effluent, in which detection limits were 0.13-1.3 ng L(-1) (free), 0.11-1.0 ng L(-1) (conjugated), and 0.18-18 ng L(-1) (halogenated). An aqueous phase additive, ammonium fluoride, was used to increase the electrospray (negative mode) ionization efficiency of free and halogenated estrogens by factors of 20 and 2.6, respectively. The method was validated using treated effluent from the greater Boston metropolitan area, where conjugated and halogenated estrogens made up 60-70% of the steroidal estrogen load on a molar basis.

Children with short bowel syndrome face life-threatening complications. Therefore, there is an urgent need for a new therapy to induce effective adaptation of the remnant intestine. Adaptation occurs only during feeding. We focused on preprandial acyl ghrelin and des-acyl ghrelin, and postprandial glucagon-like peptide-2 (GLP-2), which are known to have active orexigenic and trophic actions. This study aims to clarify the secretion trends of these hormones after massive small bowel resection and to obtain basic data for developing a new treatment. Sixty-three growing male rats were used: 3 were designated as controls receiving no operation and 60 were randomized into the 80% small bowel resection (80% SBR) group and the transection and re-anastomosis group. Changes in body weight, food intake, and remnant intestine morphology were also assessed for 15 days after the operation. Acyl ghrelin and des-acyl ghrelin levels increased immediately, equivalently in both operation groups (P = 0.09 and 0.70). Interestingly, in 80% SBR animals, des-acyl ghrelin peaked on day 1 and acyl ghrelin peaked on day 4 (P = 0.0007 and P = 0.049 vs controls). GLP-2 secretion was obvious in 80% SBR animals (P = 2.25 × 10^{−6}), which increased immediately and peaked on day 4 (P = 0.009 vs. controls). Body weight and food intake in 80% SBR animals recovered to preoperative levels on day 4. Morphological adaptations were evident after day 4. Our results may suggest a management strategy to reinforce these physiological hormone secretion patterns in developing a new therapy for short bowel syndrome.

Background Chronic intestinal pseudo-obstruction (CIPO) is a rare disabling and life-threatening disorder characterized by severe impairment of gastrointestinal peristalsis. While a number of pharmacotherapeutics have been developed, only a few trials have been carried out for improvement of the pathological condition of CIPO patients. This report describes the results of a nationwide survey on the pharmacotherapy used in pediatric CIPO in Japan. Methods In 2012, a nationwide survey was conducted to identify the clinical presentation of CIPO in Japan. Information was gathered on pharmacotherapy. Four categories were created for medicines used in pharmacotherapy: “probiotics”, “Japanese herbal medicines (Kampo medicines)”, “laxatives”, and “prokinetics”. Results Ninety-two responses were collected from 47 facilities. Of the 62 patients who met the diagnostic criteria, 52 were treated with medications, while the remaining 10 were not. Thirty-four patients were given a total of 49 probiotics; 39 were treated with a total of 50 Kampo medicines; 20 were treated with a total of 28 laxatives; and 26 were given a total of 30 prokinetics, 70% of whom were treated specifically with mosapride. Conclusion Traditional Japanese medicines such as Kampo medicines and mosapride are often used to treat CIPO in Japan. Two combinations, that is, probiotics and Kampo medicines; and Kampo medicines and prokinetics, were often used for pediatric CIPO in Japan.

Interleukin-1 beta (IL-1β) induces endothelial dysfunction and reduces nitric oxide (NO) production. IL-1β also enhances adhesion molecule expression and induces arteriosclerosis. Conversely, high-density lipoprotein (HDL) induces endothelial NO synthase (eNOS), paraoxonase-1 (PON-1) activity, and maintains vascular health. Diet-derived β-carotene prevents arteriosclerosis, but its mode of action is not understood. The purpose of this study was to examine the HDL-like mechanisms of β-carotene in endothelial cells. We added IL-1β and/or β-carotene to cultured human endothelial cells and examined its effects on the regulation of HDL signal transduction pathways using RT-PCR, real-time PCR, Western blot (WB), and endothelial-U937 adhesion analysis. IL-1β decreased the expression of Ca2+/calmodulin-dependent kinase II (CaMKII), eNOS, PON-1, phosphatidylinositol 3-kinase (PI3K), PSD-95/Dlg/ZO-1 (PZK1), and liver kinase B1 (LKB1). Conversely, it increased the expression of intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein 1 (MCP-1). In contrast, β-carotene increased the expression of CaMKKII, PI3K, PZK1, LKB1, eNOS, PON-1, and reduced the expression of ICAM-1 and MCP-1. β-carotene also induced phospho-AMP-activated protein kinase (p-AMPK), phospho-eNOS and PON-1 proteins. Importantly, β-carotene upregulated the IL-1β-mediated decrease of CaMKKII, PZK1, LKB1, eNOS and PON-1. β-carotene inhibited IL-1β-mediated cell adhesion of U937 to endothelial cells. The effect of β-carotene was reversed by a CaMKK inhibitor, STO-609. These findings indicate that β-carotene regulates the expression of PON-1, eNOS and adhesion molecules via CaMKK pathway activation. β-carotene may contribute to the functional maintenance of vascular endothelial cells in a manner similar to HDL, protecting them against stimuli such as IL-1β.

The early stages of vascular endothelial dysfunction enhance angiogenic stimulation and strongly influence vascular rearrangement. The aim of this study was to determine whether a short period of high glucose (HG, 30 mM glucose) plus tumor necrosis factor alpha (TNFα) treatment or reoxygenation after hypoxia (H/R) alters the expression levels of apelin in human endothelial cells. In addition, we also examined the effects of the dietary flavonoid apigenin on apelin expression. Human endothelial cell lines were treated with HG plus TNFα or subjected to H/R. The expression levels of genes and proteins were then assessed by the reverse transcriptase polymerase chain reaction, Western blotting and immunofluorescence analyses. The expression level of apelin was significantly higher in the HG group following exposure to reoxygenation or TNFα. Reoxygenation after hypoxia decreased the expression levels of apelin and fatty acid transport protein (FATP) 1 compared with those observed during hypoxia alone and normoxia in a normal glucose concentration. Inversely, apigenin augmented H/R-reduced apelin and FATP1 expression in endothelial cells. Based on our findings, we propose that the early stages of endothelial disorder subtly influence angiogenesis and that HG and H/R stimulate vascular rearrangement and are involved in fatty acid uptake. Furthermore, dietary apigenin might improve the expression of angiogenic genes and fatty acid uptake.

We describe a prenatally diagnosed case with congenital infantile fibrosarcoma, which is a rare malignant tumor, of which there have been only 14 cases reported in the English literature. A giant mass on the left thigh was detected at 24 weeks' gestation by prenatal ultrasonography. Because of its rapid growth and nonreassuring fetal status in utero, the baby was delivered by cesarean delivery at 27 weeks' gestation. The case was complicated by hemorrhagic anemia, coagulopathy, and cardiac failure, and a tumor resection was performed on day 3. As of age 2.5 years, he was healthy without evidence of recurrence. Because some fetal cases with congenital infantile fibrosarcoma have a poor prognosis, termination of pregnancy at an appropriate time and postnatal early treatment are crucial for successful treatment.

我が国におけるゴマ葉の食習慣はほとんどないが，アジアやアフリカではゴマ葉は食用として，あるいは伝統薬・民間薬として利用されている．このゴマ葉はポリフェノールを豊富に含むものの，その成分研究はほとんど行われておらず，不明な点が多い．そこで，ゴマ若葉中の豊富なポリフェノールに着目し，抗酸化性と活性成分について検討した結果，以下の知見を得た．（1） 3つのラジカル消去測定（DPPHラジカル消去活性，ABTSラジカル消去活性，スーパーオキシドアニオンラジカル消去活性）により評価したところ，どの測定法においてもゴマ若葉は大麦若葉やケールよりも高い抗酸化性を示し，その活性は桑葉に次ぐものであった．この活性は含有ポリフェノール量に依存した．（2） ポリフェノール含量当たりで抗酸化性を評価したところ，どの測定法においてもゴマ若葉と桑葉の活性差は小さくなり，中でもDPPHラジカル消去活性ではゴマ若葉は桑葉よりも強い活性を示したことから，ゴマ若葉には強い抗酸化性を示すポリフェノール成分が含まれると考えられた．（3） DPPHポストカラム法を用いて，含有成分並びに活性関与成分を調べたところ，ゴマ若葉中には少なくとも9つのポリフェノール成分が含まれ，うち4つが主要な活性成分であると考えられた．（4） 各種スペクトル分析の結果，主要活性成分の一つはフェニルプロパノイド配糖体であるアクテオシドであり，ゴマ若葉乾燥粉末中に1.2％含まれることが判明した．アクテオシドは様々な生理機能を有し，種々の薬用植物に存在することが明らかにされているが，豊富に含む植物は希である．本研究により，ゴマ若葉にアクテオシドが豊富に含まれることが判明したことから，今後アクテオシドを指標としたゴマ若葉の有効利用が期待される．