Mogrol stimulates G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and insulin secretion from pancreatic ß-cells and alleviates hyperglycemia in mice.

Target identification is a crucial step in elucidating the mechanisms by which functional food components exert their functions. Here, we identified the G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) as a target of the triterpenoid mogrol, a class of aglycone mogroside derivative from Siraitia grosvenorii. Mogrol, but not mogrosides, activated cAMP-response element-mediated transcription in a TGR5-dependent manner. Additionally, mogrol selectively activated TGR5 but not the other bile acid-responsive receptors (i.e., farnesoid X receptor, vitamin D receptor, or muscarinic acetylcholine receptor M3). Several amino acids in TGR5 (L71A2.60, W75AECL1, Q77AECL1, R80AECL1, Y89A3.29, F161AECL2, L166A5.39, Y240A6.51, S247A6.58, Y251A6.62, L262A7.35, and L266A7.39) were found to be important for mogrol-induced activation. Mogrol activated insulin secretion under low-glucose conditions in INS-1 pancreatic ß-cells, which can be inhibited by a TGR5 inhibitor. Similar effects of mogrol on insulin secretion were observed in the isolated mouse islets. Mogrol administration partially but significantly alleviated hyperglycemia in KKAy diabetic mice by increasing the insulin levels without affecting the ß-cell mass or pancreatic insulin content. These results suggest that mogrol stimulates insulin secretion and alleviates hyperglycemia by acting as a TGR5 agonist.

Epidemiology of child mortality and challenges in child death review in Japan: The Committee on Child Death Review: A Committee Report: The Committee on Child Death Review: A Committee Report.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language.

Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy.

OBJECTIVE: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. METHODS: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm-2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. RESULTS: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. CONCLUSION: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure.

Variations in ORAI1 Gene Associated with Kawasaki Disease.

Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca(2+)/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca(2+) release activated Ca(2+) (CRAC) channel mediating store-operated Ca(2+) entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair in-frame insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca(2+)/NFAT pathway in the pathogenesis of this disorder.

Placental mesenchymal dysplasia differentially diagnosed from molar pregnancy by 3-D inversion mode rendering: a case report.

Placental mesenchymal dysplasia (PMD) is a rare placental vascular anomaly which resembles partial molar pregnancy by 2-D ultrasonography. It is challenging but clinically important to distinguish between them in order to avoid unnecessary termination of pregnancy. A patient was referred to our centre at 13 weeks of gestation and 2-D ultrasound of the placenta showed a widespread vesicular pattern mixed with normal appearing placenta. Amniotic fluid volume was normal, and the fetus appeared to be an appropriate size for gestation without obvious structural abnormalities. 3-D reconstruction imaging of the placenta showed a large multi-cystic area arising from the chorionic plate which was adjacent to normal-appearing placenta. 3-D imaging rendered with 'inversion mode' revealed multiple fluid-filled structures with different sizes and appearances. Her serum hCG level was slightly elevated. All findings taken together, we suspected PMD rather than partial molar pregnancy. Histological examinations of the placenta after termination at 15 weeks confirmed the diagnosis.

Grave outcome of granulocyte colony-stimulating factor-producing endometrial cancer: a case report and literature review.

Granulocyte colony-stimulating factor (G-CSF)-producing nonhematopoietic malignancies have been reported in various organs, and most of them have been associated with poor clinical outcome. However, because of the rarity of reported cases, information regarding G-CSF-producing gynecological malignancies, especially uterine corpus cancer, is limited. We report a case of G-CSF-producing endometrial cancer, which exhibited a grave clinical outcome. Our case strongly indicates the aggressive nature of G-CSF-producing endometrial cancer.

Japanese guidelines for the management of intussusception in children, 2011.

BACKGROUND: The Japanese Society of Emergency Pediatrics has formulated evidence-based guidelines for the management of intussusception in children in order to diagnose intussusceptions promptly, to initiate appropriate treatment as early as possible, and to protect intussuscepted children from death. METHODS: Literature was collected systematically via the Internet using the key words "intussusception" and "children." The evidence level of each paper was rated in accordance with the levels of evidence of the Oxford Center for Evidence-based Medicine. The guidelines consisted of 50 clinical questions and the answers. Grades of recommendation were added to the procedures recommended on the basis of the strength of evidence levels. RESULTS: Three criteria of "diagnostic criteria,""severity assessment criteria," and "criteria for patient transfer" were proposed aiming at an early diagnosis, selection of appropriate treatment, and patient transfer for referral to a tertiary hospital in severe cases. Barium is no longer recommended for enema reduction (recommendation D) because the patient becomes severely ill once perforation occurs. Use of other contrast media, such as water-soluble iodinated contrast, normal saline, or air, is recommended under either fluoroscopic or sonographic guidance. Delayed repeat enema improves reduction success rate, and is recommended if the initial enema partially reduced the intussusception and if the patient condition is stable. CONCLUSIONS: The guidelines offer standards of management, but it is not necessarily the purpose of the guidelines to regulate clinical practices. One should judge each individual clinical situation in accordance with experiences, available devices, and the patient's condition.

A genome-wide association study identifies three new risk loci for Kawasaki disease.

We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10(-21)), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10(-11)) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10(-8)). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10(-6)) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.

Characteristics of neuropsychological functions in inpatients with poorly-controlled type 2 diabetes mellitus.

UNLABELLED: Aims/Introduction: It has been suggested that type 2 diabetes is associated with cognitive impairment. We investigated the neuropsychological profile of inpatients with poorly controlled type 2 diabetes and assessed the effects of clinical factors on neuropsychological functions. MATERIALS AND METHODS: Forty-two patients with type 2 diabetes and 32 non diabetic control subjects were matched for age, sex ratio, and level of education. Attention & working memory, processing speed, verbal memory, visuospatial memory, visuoconstruction, and executive function were tested. Information about physical function, alcohol use, hypertension, dyslipidemia, and myocardial infarction was retrieved from personal interviews and medical records. RESULTS: Diabetic patients demonstrated mild cognitive deterioration in attention & working memory, processing speed, verbal memory, and executive function. In particular, neuropsychological decline became prominent when tasks related with speed and verbal stimuli became unstructured and complex. Age was significantly associated with the majority of neuropsychological tests, whereas tasks dealing with working memory and executive function were associated with age only in the diabetic group. Duration of diabetes was associated with Backward Digit Span. CONCLUSIONS: Accelerated aging had a major influence on cognitive decline in the diabetic group, whereas diminished performance in working memory and executive function might have been more related to diabetes-related cognitive impairment. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00170.x, 2011).

Effects of blood glucose level on FDG uptake by liver: a FDG-PET/CT study.

UNLABELLED: In FDG-PET for abdominal malignancy, the liver may be assumed as an internal standard for grading abnormal FDG uptake both in early images and in delayed images. However, physiological variables of FDG uptake by the liver, especially the effects of blood glucose level, have not yet been elucidated. METHODS: FDG-PET studies of 70 patients examined at 50 to 70 min after injection (60 ± 10 min: early images) and of 68 patients examined at 80 to 100 min after injection (90 ± 10 min: delayed images) were analyzed for liver FDG uptake. Patients having lesions in the liver, spleen and pancreas; patients having bulk tumor in other areas; and patients early after chemotherapy or radiotherapy were excluded; also, patients with blood glucose level over 125 mg/dl were excluded. RESULTS: Mean standardized uptake value (SUV) of the liver, blood glucose level and sex showed no significant differences between early images and delayed images. However, liver SUV in the delayed image showed a larger variation than that in the early image and showed significant correlation to blood glucose level. The partial correlation coefficient between liver SUV and blood glucose level in the delayed image with adjustment for sex and age was 0.73 (P < .0001). Multivariate regression coefficient (95% confidence interval) of blood glucose was 0.017 (0.013-0.021). CONCLUSION: Blood glucose level is an important factor affecting the normal liver FDG uptake in nondiabetic patients. In the case of higher glucose level, liver FDG uptake is elevated especially in the delayed image. This may be due to the fact that the liver is the key organ responsible for glucose metabolism through gluconeogenesis and glycogen storage.

Human C-reactive protein enhances vulnerability of immature rats to hypoxic-ischemic brain damage: a preliminary study.

In utero exposure to infection or inflammation is a strong and independent predictor of cerebral palsy. Using a rat model of neonatal hypoxic-ischemic (HI) encephalopathy, we investigated the hypothesis that C-reactive protein (CRP), which is not specific for infection, aggravates vulnerability of the immature brain to HI. Seven-day-old rats were divided into human CRP treated and control groups. After injection of each solution, they underwent left common carotid artery ligation and exposure to 8% hypoxia for 40 minutes. Human CRP, rat CRP, and interleukin 6 (IL-6) concentrations in serum were measured by enzyme-linked immunosorbent assay 30 to 60 minutes after injection of each solution. Four days later, microtubule-associated protein 2 (MAP-2) immunostaining was used to examine the brains for neuronal damage. Human CRP treatment significantly reduced the MAP-2 positive area ratio, compared with control group ( P < .05), suggesting that human CRP-enhanced susceptibility to HI-induced brain damage. Mean serum human CRP concentration in the human CRP group was 1823 +/- 520 ng/mL (range: 365-3964 ng/mL). Interleukin 6 concentrations in serum were moderately elevated in both groups, without significant differences, and rat CRP concentrations were within normal range. C-reactive protein makes the immature brain susceptible to HI insult, even if the insult causes little or no injury by itself.

Digestion and absorption of Siraitia grosvenori triterpenoids in the rat.

When administered to rats, mogroside V (a pentaglucose-conjugated mogroside), the main sweetening component of Siraitia grosvenori, was mostly degraded by digestive enzymes and intestinal microflora, and was excreted in the feces as mogrol (aglycone) and its mono- and diglucosides. However, trace amounts of mogrol and its monoglucoside were found in the portal blood as sulfates and/or glucuronide conjugates.

[18F]Fluorodeoxyglucose-PET/CT differentiation between physiological and pathological accumulations in head and neck.

OBJECTIVES: The purposes of this study were to evaluate various physiological fluorodeoxyglucose (FDG) accumulations in the head and neck and to compare those with tumor (pathological) FDG accumulation. METHODS: One hundred and twelve patients with head and neck carcinomas were studied. PET/computed tomography examinations were performed 1 h after intravenous injection of fluorine-18-labeled FDG. The tumor and the physiological FDG accumulations were identified with PET/computed tomography images, and the maximum of the standardized uptake value (SUVmax) was calculated. RESULTS: Physiological FDG accumulation was observed in tonsil, extraocular muscle, masticatory muscle, vocal cord, and the major salivary glands: parotid, submandibular, and sublingual gland. The accumulation in tonsil, extraocular muscle, and sublingual gland showed relatively high SUVmax. The tumor FDG accumulation was significantly higher than any physiological FDG accumulation. The optimal cut-off values of SUVmax for differentiating physiological FDG accumulation from pathological FDG accumulation were 4.0 for parotid gland, 4.5 for submandibular gland, 5.5 for sublingual gland, 8.0 for tonsil, and 10.0 for extraocular muscle. The right-to-left ratio of SUVmax was less than 1.5 in any physiological accumulation. CONCLUSION: Tonsil, extraocular muscle, and sublingual gland showed relatively high FDG accumulation, which was sometimes similar to tumor accumulation. The right-to-left ratio of SUVmax was considered useful in differentiating tumor from physiological accumulation, and the presence of tumor might be highly suspected in cases with a ratio of 1.5 or more.

Suppressive effect of Siraitia grosvenorii extract on dicyclanil-promoted hepatocellular proliferative lesions in male mice.

Dicyclanil (DC) generates reactive oxygen species (ROS) due to Cyp1a1 induction, and DNA damage caused by oxidative stress is probably involved in hepatocarcinogenesis in mice. To clarify the modifying effect of the Siraitia grosvenorii extract (SGE), which has antioxidative properties, we employed a 2-stage liver carcinogenesis model in partially hepatectomized male ICR mice. Mice maintained on diet containing DC at a concentration of 1,500 ppm for 9 weeks after a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 30 mg/kg and they were given water containing 2,500 ppm of SGE for 11 weeks including 2 weeks as pre-administration on DC. SGE inhibited the induction of gamma-glutamyltranspeptidase-positive hepatocytes, lipid peroxidation, and gene expression of Cyp1a1, all of which were caused by DC. To examine whether SGE indirectly inhibits Cyp1a1 expression induced by inhibition of aryl hydrocarbon receptor (Ahr)-mediated signal transduction caused by DC, mice with high (C57BL/6J mice) and low affinities (DBA/2J mice) to Ahr were given DC-containing diet and/or SGE-containing tap water for 2 weeks. Cyp1a1 gene expression was significantly lower in C57BL/6J mice administered DC + SGE than in C57BL/6J mice administered DC alone; there was no difference in the Cyp1a1 expression between DBA/2J mice administered DC + SGE and DC alone. These results suggest that SGE suppresses the induction of Cyp1a1, leading to inhibition of ROS generation and consequently inhibited hepatocarcinogenesis, probably due to suppression of Ahr activity.

A case of disseminated peritoneal leiomyomatosis developing after laparoscope-assisted myomectomy.

A 36-year-old nulliparous woman developed multiple extra-uterine fibroids in the pelvic cavity years after laparoscopic myomectomy. Molecular genetic analysis by methylation-specific polymerase chain reaction (MSPCR) of the human X-linked androgen receptor gene and loss of heterozygosity (LOH) analysis at 5 microsatellite loci was performed on the tumors. All tumors showed an identical non-random X-chromosome inactivation pattern by MSPCR and an identical pattern of LOH was found in all the tumors by LOH analysis. This demonstrated that 3 fibroids resected 2 years later and 14 fibroids resected 6 years later were all metastatic tumors originating from the uterine leiomyoma found during the initial surgery, suggesting that morcellation before removal of the leiomyoma nodule during laparoscopic myomectomy may have been associated with the pathogenesis of this case.

Usefulness of PET/CT for detecting a second primary cancer after treatment for squamous cell carcinoma of the head and neck.

PURPOSE: Patients with squamous cell carcinoma of the head and neck have been reported to have a high rate of second primary cancer of the upper aerodigestive tract. This study was performed to determine whether positron emission tomography/computed tomography (PET/CT) is useful for detecting a second primary cancer after treatment for squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: The PET/CT findings in 279 consecutive patients (211 men, 68 women; mean age 62 years) who had been treated for squamous cell carcinomas of the head and neck were examined and compared with the findings obtained by other imaging modalities, the biopsy results, and the clinical data. RESULTS: Thirty second primary cancers were documented in 28 of the 279 subjects. Based on PET/CT findings, the overall risk of a second primary cancer in 1 year was 9.9% and the risk in the upper aerodigestive tract region was 6.8% (19/279). CONCLUSIONS: PET/CT enabled early detection of a second cancer in patients treated for head and neck cancer.

(18)F-FDG-PET/CT findings of granulocyte colony stimulating factor (G-CSF)-producing lung tumors.

Tumors producing granulocyte colony stimulating factor (G-CSF), malignant lung tumors in most cases, are rare, and patients present with abnormal elevations of the white blood cell (WBC) count in the absence of any infectious disease. We present the (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) imaging findings of two cases of G-CSF-producing tumor. PET-CT showed abnormally high uptake of (18)F-FDG not only by the tumor itself but also diffusely throughout the bone marrow. Following resection of the tumor, the blood G-CSF level as well as the WBC count dropped down to normal range in both cases. Histopathological examination of the resected tumor specimens revealed the presence of an enormous number of inflammatory cells within the tumors and positive immunostaining of the tumor cells for G-CSF. The (18)F-FDG-PET/CT findings could be explained by the elevated bone marrow metabolism associated with the excessively active production of granulocytes under G-CSF stimulation, and the (18)F-FDG uptake by the inflammatory cells also contributing to the total tumor uptake of (18)F-FDG. These characteristic imaging findings are expected to be useful for the diagnosis of G-CSF-producing tumors.

A1C but not serum glycated albumin is elevated in late pregnancy owing to iron deficiency.

OBJECTIVE: A1C levels have been shown to be elevated in relation to glycemia in late pregnancy, although the precise mechanisms remain undetermined. We hypothesized that iron deficiency is involved in the A1C increase in late pregnancy. RESEARCH DESIGN AND METHODS: In study 1, A1C, serum glycated albumin, erythrocyte indexes, and iron metabolism indexes were determined in 47 nondiabetic pregnant women not receiving iron supplementation who were divided into four groups according to gestational period (group I, 21-24 weeks; group II, 25-28 weeks; group III, 29-32 weeks; and group IV, 33-36 weeks). In study 2, these determinants were obtained at two gestational periods (20-23 weeks and 32-33 weeks) in 17 nondiabetic pregnant women. RESULTS: In study 1, A1C levels were higher in groups III and IV than those in groups I and II, whereas serum glycated albumin levels were not different among these four groups. Hemoglobin, mean corpuscular hemoglobin (MCH), serum transferrin saturation, and serum ferritin were lower in groups III and IV. A1C levels were negatively correlated with MCH, serum transferrin saturation, and serum ferritin. In study 2, A1C levels were significantly increased at gestational weeks 32-33 from those at weeks 20-23, whereas serum glycated albumin levels did not differ between the two gestational periods. MCH, serum transferrin saturation, and serum ferritin were decreased at gestational weeks 32-33. A1C levels showed a negative correlation with MCH, serum transferrin saturation, and serum ferritin. CONCLUSIONS: A1C levels were elevated in late pregnancy owing to iron deficiency. Serum glycated albumin may offer a better index for monitoring glycemic control in pregnancy.

Modifying effect of Siraitia grosvenori extract on piperonyl butoxide-promoted hepatocarcinogenesis in rats.

To examine the possible modifying effect of the extract of Siraitia grosvenori (SGE), a naturally occurring antioxidative agent, on piperonyl butoxide (PBO)-promoted hepatocarcinogenesis, male F344 rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) as an initiator followed by administration of a diet containing 2% PBO for 7 weeks with or without SGE (1,000 ppm) in the drinking water. To enhance cellular proliferation, all animals underwent two-thirds partial hepatectomy 1 week after the commencement of PBO administration. Pretreatment with SGE was also applied to the PBO + SGE group for 2 weeks prior to DEN initiation. Liver immunohistochemistry revealed that although the PBO-mediated increase in the number of glutathione S-transferase placental form (GST-P)-positive foci and proliferating cell nuclear antigen-positive cells remained unaltered with SGE coadministration, the area of the GST-P-positive foci was increased. On the contrary, real-time RT-PCR showed that coadministration of SGE increased hepatic GST and glutathione peroxidase (GSH-Px) antioxidant activities and mRNA expression levels of the phase II enzymes that are known to be transcriptionally up-regulated through the Nrf 2-Keap1-antioxidant responsive element (ARE) as well as the phase III enzymes. Furthermore, measurement of thiobarbituric acid-reactive substances showed a decrease in lipid peroxidation by SGE coadministration. The results suggest that SGE may exert hepatic antioxidant activity by up-regulating the genes under the control of the Nrf 2-Keap1-ARE transcriptional machinery; however, this activity was neither effective nor sufficient for suppression of PBO-promoted early hepatocarcinogenesis.

PET/CT evaluation of the physiologic accumulation of 18F-FDG within the gallbladder vesicle.

The aim of this study was to investigate physiological fluorine 18-labeled fluourodeoxyglucose accumulation in the gallbladder (GB) during clinical positron emission tomography (PET) examinations. Three patient groups were included. In Group 1, nine patients with higher fluourodeoxyglucose (FDG) accumulation in the GB than in the liver were examined, followed up and finally diagnosed. In Group 2, the correlations between FDG GB accumulation and various parameters in 286 patients were investigated. In Group 3, changes in FDG GB accumulation between early and delayed PET scans were analyzed in 12 patients. In Group 1, all nine patients who exhibited a high FDG GB accumulation had no evidence of GB disease. In Group 2, FDG GB accumulation was significantly correlated with the injection-scan time interval and inversely correlated with the GB size index. Group 3 showed a significant increase in FDG accumulation in the GB on delayed PET scans, compared with that seen on early scans. In clinical PET studies, FDG accumulation within the GB is infrequently observed but may be due to FDG excretion into the bile. Recognition of this phenomenon may be important to avoid misdiagnosing physiological GB FDG accumulation as indicating a pathologic status and preventing unnecessary examinations.