Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice.

PURPOSE: Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. METHODS: The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. RESULTS: Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. CONCLUSIONS: Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.

Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice.

Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into two groups and fed a normal diet (ND) or a low-iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared with the LID group. Augmented deposition of extracellular matrixes was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NADPH oxidase 4 (NOX4) were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress.

Association of severe COVID-19 outcomes with radiological scoring and cardiomegaly: findings from the COVID-19 inpatients database, Japan.

PURPOSE: We aimed to characterize novel coronavirus infections based on imaging [chest X-ray and chest computed tomography (CT)] at the time of admission. MATERIALS AND METHODS: We extracted data from 396 patients with laboratory-confirmed COVID-19 who were managed at 68 hospitals in Japan from January 25 to September 2, 2020. Case patients were categorized as severe (death or treatment with invasive ventilation during hospitalization) and non-severe groups. The imaging findings of the groups were compared by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for sex, age, and hospital size (and radiographic patient positioning for cardiomegaly). Chest X-ray and CT scores ranged from 0 to 72 and 0 to 20, respectively. Optimal cut-off values for these scores were determined by a receiver-operating characteristic (ROC) curve analysis. RESULTS: The median age of the 396 patients was 48 years (interquartile range 28-65) and 211 (53.3%) patients were male. Thirty-two severe cases were compared to 364 non-severe cases. At the time of admission, abnormal lesions on chest X-ray and CT were mainly observed in the lower zone/lobe. Among severe cases, abnormal lesions were also seen in the upper zone/lobe. After adjustment, the total chest X-ray and CT score values showed a dose-dependent association with severe disease. For chest X-ray scores, the area under the ROC curve (AUC) was 0.91 (95% CI = 0.86-0.97) and an optimal cut-off value of 9 points predicted severe disease with 83.3% sensitivity and 84.7% specificity. For chest CT scores, the AUC was 0.94 (95% CI = 0.89-0.98) and an optimal cut-off value of 11 points predicted severe disease with 90.9% sensitivity and 82.2% specificity. Cardiomegaly was strongly associated with severe disease [adjusted OR = 24.6 (95% CI = 3.7-166.0)]. CONCLUSION: Chest CT and X-ray scores and the identification of cardiomegaly could be useful for classifying severe COVID-19 on admission.

A reduced physiological 18F-fluorodeoxyglucose uptake in the brain and liver caused by malignant lymphoma being deprived of the tracer.

Purpose : To investigate whether or not the physiological brain and liver FDG uptake are decreased in patients with highly accelerated glycolysis lesions. Methods : We retrospectively analyzed 51 patients with malignant lymphoma. We compared the FDG uptake in the brain and liver of the patients with that in a control group. In 24 patients with a complete response (CR) or partial response (PR) to treatment, we compared the brain and liver uptake before and after treatment. Results : The maximum standardized uptake value (SUVmax) and total glycolytic volume (TGV) of the brain as well as the SUVmax and mean standardized uptake value (SUVmean) of the liver in malignant lymphoma patients were 13.1 ±â€…2.3, 7386.3 ±â€…1918.4, 3.2 ±â€…0.5, and 2.3 ±â€…0.4, respectively ; in the control group, these values were 14.9 ±â€…2.4, 8566.2 ±â€…1659.5, 3.4 ±â€…0.4, and 2.5 ±â€…0.3, respectively. The SUVmax and TGV of the brain and the SUVmean of the liver in malignant lymphoma patients were significantly lower than the control group. The SUVmax and TGV of the brain after treatment were significantly higher than before treatment. Both the SUVmax and SUVmean of liver after treatment were higher than before treatment, but not significant. Conclusion : A decreased physiological brain and liver FDG uptake is caused by highly accelerated lesion glycolysis. J. Med. Invest. 68 : 181-185, February, 2021.

Ultraselective transcatheter arterial embolization with small-sized microcoils for acute lower gastrointestinal bleeding.

PURPOSE: To evaluate the clinical outcome of ultraselective transcatheter arterial embolization (TAE) with small-sized microcoils for acute lower gastrointestinal bleeding (LGIB). MATERIALS AND METHODS: The subjects were 17 consecutive patients (mean age, 69 years) with LGIB who were treated with ultraselective TAE using small-sized microcoils between December 2013 and December 2019. Ultraselective TAE was defined as embolization of one or both of the long or short branches of the vasa recta. The etiologies of bleeding were colonic diverticulosis in 16 patients (94%) and malignancy in one patient (6%). The bleeding foci were in the ascending colon in 11 patients (65%), transverse colon in 2 patients (12%), and sigmoid colon in 4 patients (23%). A total of 18 branches (diameter: range 0.5-1.5 mm, mean 1.1 mm) of the vasa recta in 17 patients were embolized with small-sized microcoils (size range 1-3 mm, mean combined lengths of all microcoils 7.6 cm). The mean follow-up period was 19 months (range 1-80 months). The technical and clinical success rate, recurrent bleeding rate, major complications and long-term clinical outcomes were retrospectively evaluated. RESULTS: Technical and clinical success was achieved in all patients (17/17). The rates of early recurrent bleeding (within 30 days of TAE) and major complications were 0% (0/17). Recurrent bleeding occurred in one patient at 2 months after TAE, but was stopped with conservative treatment. There were no other bleeding episodes or complications in the follow-up period. CONCLUSION: Ultraselective TAE with small-sized microcoils is a highly effective and safe treatment modality for LGIB.