A Retinoid X Receptor Agonist Directed to the Large Intestine Ameliorates T-Cell-Mediated Colitis in Mice

Retinoid X receptor (RXR) is a nuclear receptor that heterodimerizes with several nuclear receptors, integrating ligand-mediated signals across the heterodimers. Synthetic RXR agonists have been developed to cure certain inflammatory diseases, including inflammatory bowel diseases (IBDs). However, pre-existing RXR agonists, which are lipophilic and readily absorbed in the upper intestine, cause considerable adverse effects such as hepatomegaly, hyperlipidemia, and hypothyroidism. To minimize these adverse effects, we have developed an RXR agonist, NEt-3IB, which has lipophilic and thus poorly absorptive properties. In this study, we evaluated the effects of NEt-3IB in an experimental murine colitis model induced through the adoptive transfer of CD45RB(high)CD4(+) T cells. Pharmacokinetic studies demonstrated that the major portion of NEt-3IB was successfully delivered to the large intestine after oral administration. Notably, NEt-3IB treatment suppressed the development of T cell-mediated chronic colitis, as indicated by improvement of wasting symptoms, inflammatory infiltration, and mucosal hyperplasia. The protective effect of NEt-3IB was mediated by the suppression of IFN-gamma-producing Th1 cell expansion in the colon. In conclusion, NEt-3IB, a large intestine-directed RXR agonist, is a promising drug candidate for IBDs

Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: “Gestational trophoblastic disease AND Ultrasonography, Doppler.” Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. CONCLUSION: Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia

Sheet Dependence on Superconducting Gap in Oxygen-Deficient Iron-based Oxypnictide Superconductors NdFeAs0.85

Photoemission spectroscopy with low-energy tunable photons on oxygen-deficient iron-based oxypnictide superconductors NdFeAsO0.85 (Tc=52K) reveals a distinct photon-energy dependence of the electronic structure near the Fermi level (EF). A clear shift of the leading-edge can be observed in the superconducting states with 9.5 eV photons, while a clear Fermi cutoff with little leading-edge shift can be observed with 6.0 eV photons. The results are indicative of the superconducting gap opening not on the hole-like ones around Gamma (0,0) point but on the electron-like sheets around M(pi,pi) point.Comment: 8 pages, 3 figure

Serotonin- and Somatostatin-Positive Goblet Cell Carcinoid of the Duodenum

In the duodenum, mixed exocrine-endocrine tumors exhibiting both neuroendocrine and glandular differentiations [cf. appendiceal goblet cell carcinoids (GCCs)] are rare. We present a Japanese case with a duodenal GCC that was found during pathologic examination of a gastrectomy specimen removed for gastric mucosal cancer. The tumor was widely distributed within both the first portion of the duodenum and the gastric antrum, although mucosal involvement was observed only in the duodenum. The tumor cells formed solid nests, trabeculae, or tubules, and some displayed a goblet cell appearance. They were immunoreactive against antibodies for both serotonin and somatostatin, and showed an argentaffin reaction (similar to a “midgut” enterochromaffin cell carcinoid). Ultra-structurally, the tumor cells had an amphicrine nature. Physicians encounter GCC in the duodenum only rarely, and its discovery may be incidental. Its diagnosis will be challenging and will require careful clinical and pathologic examinations