Retinoic acid controls vascular formation by activating transcription of aryl hydrocarbon receptor gene in medakafish Oryzias latipes

Retinoic acid (RA) has been shown to have a role in vascular formation, but how it affects is not fully understood. Previously, we reported that RA and its nuclear receptor (RAR) is required for transcription of ahr1 encoding an aryl hydrocarbon receptor (AHR), and that pharmacological modulation of RA, RAR, and AHR impairs the formation of common cardinal veins (CCVs) on the yolk of medakafish embryos. Here, to delineate a role for ahr1 in the vascular formation, we used an antisense-ahr1 mRNA to suppress ahr1. Following the development of vegfr1-expressing angioblast cells, we show that the antisense-ahr1 greatly inhibited the accumulation of angioblasts at the prospective branchial arch (PBA) where CCVs begin to develop on the yolk and the following CCV formation, demonstrating for the first time the essential role of ahr1 in the embryonic vascular formation of vertebrates. We also show that rarα and ahr1 mRNAs are co-expressed at PBA, suggesting a possible role of the specific expression.This work was supported in part by a grant from the Ministry of Education, Science, Sports and Culture of Japan

Maternal estrogen controls retinoic acid metabolism and signaling in early vertebrate development

Fertilized eggs of lower vertebrates contain substantial amounts of steroidal hormones such as estrogen transferred from mother during oogenesis. However, molecular roles for maternal estrogen in the early embryonic development are largely unknown. Here we show that maternal estrogen and estrogen receptor-α modulate retinoic acid (RA) metabolism and RA-responsive gene expression in medaka embryos. Treatments with excess estradiol, an anti-estrogen (tamoxifen), overexpression or knockdown of estrogen receptor-α (ERα) resulted in misregulation of RA-related gene expression such as raldh2 (retinalaldehyde dehydrogenase), cyp26a1 (RA hydroxylase), fgf8 (fibroblast growth factor), rarα (RA receptor-α), and ahr1 (aryl hydrocarbon receptor). We propose that maternal estrogen/ERα plays a critical role in the feedback control of in vivo level of RA and that it also activates RA signaling for the development of hindbrain and vasculatures. This is the first report demonstrating that maternal estrogen supports successful embryonic development by controlling RA metabolism and signaling in early vertebrate embryos.Supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan

Current status of active cooling, deep body temperature measurement, and face mask wearing in heat stroke and heat exhaustion patients in Japan: a nationwide observational study based on the Heatstroke STUDY 2020 and 2021

Aim The study aimed to determine the current status of face mask use, deep body temperature measurement, and active cooling in patients suffering from heat stroke and heat exhaustion in Japan. Methods This was a prospective, observational, multicenter study using data from the Heatstroke STUDY 2020–2021, a nationwide periodical registry of heat stroke and heat exhaustion patients. Based on the Bouchama heatstroke criteria, we classified the patients into two groups: severe and mild‐to‐moderate. We compared the outcomes between the two groups and reclassified them into two subgroups according to the severity of the illness, deep body temperature measurements, and face mask use. Cramer's V was used to determine the effect sizes for a comparison between groups. Results Almost all patients in this study were categorized as having degree III based on the Japanese Association for Acute Medicine heatstroke criteria (JAAM‐HS). However, the severe group was significantly worse than the mild‐to‐moderate group in outcomes like in‐hospital death and modified Rankin Scale scores, when discharged. Heat strokes had significantly higher rates of active cooling and lower mortality rates than heat stroke‐like illnesses. Patients using face masks often use them during labor, sports, and other exertions, had less severe conditions, and were less likely to be young male individuals. Conclusions It is suggested that severe cases require a more detailed classification of degree III in the JAAM‐HS criteria, and not measuring deep body temperature could have been a factor in the nonperformance of active cooling and worse outcomes

Evaluation of a Novel Classification of Heat-Related Illnesses: A Multicentre Observational Study (Heat Stroke STUDY 2012)

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between 1 June and 30 September 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as Stage III were significantly higher than those of patients classified as Stage I or II. There were no deaths among the patients classified as Stage I. This novel classification may avoid underestimating the severity of heat-related illness