Dose responses of scattered- and direct-X-ray-irradiated CR-39 and methylviologen-encapsulated silica nanocapsule-doped CR-39 and their mechanisms

The photoexcited emissions of direct- and scattered-X-ray-irradiated CR-39 and methylviologen-encapsulated silica nanocapsule (MV2+@SiO2 NC)-doped CR-39 were observed, and they showed a dose response. The benzophenone radical was formed in a shallow trap in CR-39 upon X-ray irradiation from 10 to 30 Gy, and the fluorescence intensity increased with the dose. Methylviologen in SiO2 NCs competitively captured electrons generated by X-ray irradiation, and the captured electrons were reverse transferred to the shallow traps with time. A minimum dose rate of 300 µGy/s was observed between 1 and 5 Gy. Finally, a dose response of less than 2 mGy for scattered X-rays was obtained in this system

Emission image of X-ray-irradiated CR-39 stick doped with methylviologen-encapsulated silica nanocapsules using LED light

Light-emitting diode (LED)-light-excited emission images of 6 MeV-X-ray (10 Gy)-irradiated CR-39 doped with methylviologen-encapsulated silica nanocapsules (MV @SiO2 NCs) were observed using an iPhone 5S for the first time. The excitation and fluorescence spectra were also observed, and the emission peak at 580 nm produced by the X-ray irradiation was confirmed. Emission intensities of 80 kV-X-ray (0.5, 1, 1.5, and 2 Gy)-irradiated CR-39 doped with MV @ SiO2 NCs could be measured using a portable fluorometer (FC-1), and a good linear relationship between their emission intensity and dose was clearly observed

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

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Isoflurane induces c-Fos expression in the area postrema of the rat

IntroductionVolatile anesthetics are speculated to cause postoperative nausea and vomiting via stimulation of the chemoreceptor trigger zone (CTZ). However, the precise mechanism underlying the emetic action of these drugs is not well understood. In this study, we assessed whether isoflurane induced the expression of c-Fos, a neuronal activation marker, in the area postrema (AP), the locus of the CTZ, in rats, which do not have vomiting action.Materials and methodsMale rats were exposed to 1.3% isoflurane for 0-240min, or to various concentrations of isoflurane (0, 1.3%, or 2.6%) for 120min. Finally, the rats were exposed to 1.3% isoflurane for 120min after ondansetron administration. After the treatments, immunohistochemistry of the rat AP was performed using c-Fos antibody staining.ResultsOne-way analysis of variance showed that isoflurane exposure significantly increased c-Fos expression in the AP; however, the rats pretreated with 4mg/kg ondansetron showed significantly decreased c-Fos expression. Moreover, we evaluated the effect of the anesthetic on inducing pica in the rats, and found that kaolin intake was not influenced by isoflurane exposure.ConclusionOverall, these results suggest that isoflurane activates AP neurons and may be involved in the emetic mechanism of isoflurane. This study further suggests the feasibility of using rats as a model for studying emetic mechanisms of drugs, despite their lack of vomit action

Influence of nitrous oxide on granule cell migration in the dentate gyrus of the neonatal rat

For several decades, the neurotoxicities of anesthetics to the developing brain have been reported by many researchers focusing on various phenomena such as apoptosis, neurodegeneration, electrophysiological aberrations, and behavioral abnormalities. According to these reports, signals via N-methyl-D-aspartate receptors (NMDA-r) and/or γ-aminobutyric acid type A receptors (GABA(A)-r) are implicated in the anesthetic neurotoxicity. On the other hand, during brain development, NMDA-r and GABA(A)-r are also recognized to play primary roles in neural cell migration. Therefore, anesthetics exposed in this period may influence the neural cell migration of neonates, and increase the number of hilar ectopic granule cells, which are reported to be a cause of continuous neurological deficits. To examine this hypothesis, we investigated immunohistochemically granule cell distribution in the hippocampal dentate gyrus of Wistar/ST rats after nitrous oxide (N2O) exposure. At postnatal day (P) 6, 5-bromo-2'-deoxyuridine (BrdU) was administered to label newly generated cells. Then, rats were divided into groups (n = 6 each group), exposed to 50% N2O at P7, and evaluated at P21. As a result, we found that ectopic ratios (ratio of hilar/total granule cells generated at P6) were decreased in rats at P21 compared with those at P7, and increased in N2O exposed rats for over 120 min compared with the other groups. These results suggest that 50% N2O exposure for over 120 min increases the ratios of ectopic granule cells in the rat dentate gyrus