Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol

Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen.     

Orally Administrated Ascorbic Acid Suppresses Neuronal Damage and Modifies Expression of SVCT2 and GLUT1 in the Brain of Diabetic Rats with Cerebral Ischemia-Reperfusion

Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid) in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex.     

Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats

We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37–45 weeks after the treatment with STZ (50 or 75 mg/kg, i.v.) and NA (350 mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules.     

Expressions of Iba1 and galectin-3 (Gal-3) in thioacetamide (TAA)-induced acute rat liver lesions

Ionized calcium binding adaptor molecule 1 (Iba1) is associated with membrane ruffling and motility of cells. Galectin-3 (Gal-3) is a β-galactoside binding animal lectin, and regulates fibrogenesis probably through transforming growth factor-β1. To evaluate macrophage properties, expressions of Iba1 and Gal-3 were investigated, in relation to macrophages expressing CD68 (ED1; reflecting increased phagocytosis) and CD163 (ED2; implying proinflammatory factor productions) in centrilobular lesions induced in rat livers with thioacetamide (TAA; 300 mg/kg body weight, once intraperitoneally). In agreement with expression patterns of CD68⁺ and CD163⁺ macrophages, cells reacting to Iba1 and Gal-3 were increased in numbers on post-injection (PI) days 1–5, peaking on day 2; thereafter, the positive cells gradually decreased to control levels until PI days 7 and 10. The increased expressions of Iba1 and Gal-3 were confirmed at mRNA levels by the RT-PCR. Double immunofluorescence staining on PI days 2 and 3 demonstrated Iba1 expression in 15–46% of CD68⁺ and CD163⁺ macrophages, and Gal-3 expression in 65–82% of CD68⁺ and CD163⁺ macrophages; Gal-3 expression was observed in 84–93% of Iba1⁺ cells. Interestingly, Gal-3 was also expressed in a small number of α-smooth muscle actin-positive myofibroblasts in fibrotic lesions developed in injured centrilobular areas. These findings indicate that macrophages with various functions can participate in development of liver lesions and resultant fibrosis. Besides CD68 and CD163, Iba1 and Gal-3 immunohistochemistry for macrophages would be useful to analyze the pathogenesis behind developing hepatotoxicity.     

Endoscopic submucosal resection with an endoscopic variceal ligation device for the treatment of rectal neuroendocrine tumors

Background

Endoscopic resection is recommended for rectal neuroendocrine tumors <?1 cm in diameter; the three techniques (mucosal resection, submucosal dissection, and mucosal resection with variceal ligation device) of endoscopic resection of neuroendocrine tumor were reported; however, the optimal endoscopic technique remains unclear.

Purpose

We compared the efficacy and safety of three endoscopic rectal neuroendocrine tumor resection methods.

Methods

We retrospectively enrolled 52 patients with rectal neuroendocrine tumors treated by endoscopy at Aichi Medical University Hospital and Nagoya City University Hospital between May 2003 and June 2017. We compared clinical outcomes in three groups based on the endoscopic treatment method.

Results

Fifty-two patients underwent endoscopic rectal neuroendocrine tumor treatment (mucosal resection, 14; submucosal dissection, 19; mucosal resection with an endoscopic variceal ligation device, 19). In the endoscopic mucosal resection, submucosal dissection, and mucosal resection with variceal ligation device groups, R0 resection occurred in 50.0, 94.7, and 89.5%, respectively (mucosal resection vs. mucosal resection with variceal ligation device, p <?0.05; mucosal resection vs. submucosal dissection, p <?0.01), while the median procedure times were 6.5, 43, and 6.0 min, respectively (submucosal dissection vs. mucosal resection with variceal ligation device procedure times, p?<?0.01; mucosal resection vs. submucosal resection procedure times, p <?0.01). Postoperative bleeding occurred after endoscopic mucosal resection (1/14) and endoscopic submucosal dissection (4/19), but not after endoscopic mucosal resection with a ligation device.

Conclusion

Endoscopic mucosal resection with an endoscopic variceal ligation device was a safe, effective treatment for rectal neuroendocrine tumors.

     

Targeted disruption of p70s6k defines its role in protein synthesis and rapamycin sensitivity

Here, we disrupted the p70 S6 kinase (p70^s6k) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70^s6k−/− cells proliferated at a slower rate than parental cells, suggesting that p70^s6k has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70^s6k−/− cells, indicating that other events inhibited by the drug, independent of p70^s6k, also are important for both cell proliferation and the action of rapamycin. In p70^s6k−/− cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70^s6k−/− cells, indicating that these events proceed independently of p70^s6k activity. This study localizes the function of p70^s6k to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.     

Isolation of measles virus from middle ear fluid of infants with acute otitis media

Measles virus was isolated from the middle ear fluid (MEF) of two infant cases of acute otitis media (AOM) associated with measles. This is the first report on the isolation of measles virus from the MEF in patients with AOM, and possibility of the measles virus as a causative agent of AOM was suggested.