Search

Nephrolithiasis is a common renal disease with no effective medication. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, an anti-diabetic agent, have diuretic and anti-inflammatory properties and could prevent nephrolithiasis. Here, we investigated the potential of SGLT2 inhibition against nephrolithiasis using large-scale epidemiological data, animal models, and cell culture experiments.This study included the data of diabetic patients (n = 1,538,198) available in the Japanese administrative database and divided them according to SGLT2 inhibitor prescription status. For animal experiments, renal calcium oxalate stones were induced by ethylene glycol in Sprague-Dawley rats, and phlorizin, an SGLT1/2 inhibitor, was used for the treatment. The effects of SGLT2-specific inhibition for renal stone formation were assessed in SGLT2-deficient mice and a human proximal tubular cell line, HK-2.Nephrolithiasis prevalence in diabetic men was significantly lower in the SGLT2 inhibitor prescription group than in the non-SGLT2 inhibitor prescription group. Phlorizin attenuated renal stone formation and downregulated the kidney injury molecule 1 (Kim1) and osteopontin (Opn) expression in rats, with unchanged water intake and urine volume. It suppressed inflammation and macrophage marker expression, suggesting the role of the SGLT2 inhibitor in reducing inflammation. SGLT2-deficient mice were resistant to glyoxylic acid-induced calcium oxalate stone formation with reduced Opn expression and renal damages. High glucose-induced upregulation of OPN and CD44 and cell surface adhesion of calcium oxalate reduced upon SGLT2-silencing in HK-2 cells.Overall, our findings identified that SGLT2 inhibition prevents renal stone formation and may be a promising therapeutic approach against nephrolithiasis.

Electrical properties of metal/SiC/p-Si(100) structures have been examined under conditions with and without light exposure. SiC films are formed by thermal chemical vapor deposition using a monomethylsilane gas, and are amorphous. The dark current density of the metal/SiC/p-Si structure at positive voltages is lower than that at negative voltages. The difference between the photo and dark current of metal/SiC/p-Si structures is relatively large at positive voltages. A SnO2/SiC/p-Si structure has high sensitivity compared with an Al/SiC/p-Si structure. Metal/SiC/p-Si structures can be used as photodetectors at positive voltages.

We have developed an advanced infrastructure and technologies for collaborative remote operations, enabling multiple operators with large physical separation to control multiple slave robots in a common environment over the network. Human operators’ delayed visual perception arising from communication time delays seriously affects the performance of collaborative multi-site operations and accordingly requires supplementary information locally available to operators irrespective of time delays. Few facilities exist to investigate remote multi-site operations, thus we have built an experimental test bed connecting Tsukuba and Kawasaki in Japan via an integrated services digital network. In particular, an on-line predictive graphics simulator is incorporated to cope with image feedback delays from the remote site. Specifically, exploiting audio-visual features of the simulator, operators can detect a priori the possibility of collision between robots and guide them towards task goal through time delays. To verify the validity of the simulator assisted approach, we have performed a demonstration of prototype plant maintenance in April 2000 between Tsukuba and Kawasaki.

Effects of nivalenol (NIV), a trichothecene mycotoxin, on hepatic drug-metabolizing activity and aflatoxin B 1 (AFB 1 ) metabolism were investigated in male rats. In rats fed the diets containing 6–12 ppm NIV for 2 or 4 wk, decreases in initial feed uptake, terminal weight gain and organ weights were evident. An increase in cytochrome P -450 activity was observed in the hepatic microsomes, and Western blot analysis revealed a transient increase in P 4502B1/2, together with a slight induction of P 4501A2. The activity of cytosolic glutathione S -transferase (GST) enzymes was also enhanced in the rats, and Western blot analysis demonstrated an elevation of GST 1–2. The formation of aflatoxin B 1 -DNA adducts (AFB 1 DNA) was increased in experiments using hepatic microsomal preparations from rats fed the NIV diet, whereas supplementation with cytosol prepared from NIV-treated rats reduced the microsomal potential for adduct formation. In in vivo experiments, the AFB 1 DNA concentration in NIV-treated rats was lower than that in the controls. These results suggest that activities of cytochrome P − 450 and GST enzymes were increased in rats fed NIV for several weeks. Alteration of these phase 1 and phase 2 enzyme levels resulted in the modulation of AFB 1 adduction to DNA in vitro and in vivo .

We found that a 2.1-kbp KpnI fragment bearing the PDR4 (YAP1/PAR1/SNQ3) gene of Saccharomyces cerevisiae, conferring pleiotropic drug resistance to S. cerevisiae, confers resistance of the cells to 5 μg of cerulenin per ml when ligated into a multicopy vector and to 1 μg of cerulenin ligated into a single copy vector. This 2.1-kbp KpnI fragment lacks the C-terminal coding region of the published nucleotide sequence (Hussain, M. and Lenard, J.: Gene, 101, 149–152, 1991). This dosage-dependent cerulenin resistance induced by the 2.1-kbp KpnI fragment of PDR4 is useful as a dominant selective marker in genetic studies and in transformation of prototrophic S. cerevisiae strains. We constructed a pair of tester strains for mating-type determination by introducing the multicopy plasmid bearing the 2.1-kbp KpnI fragment into a and α haploid strains of S. cerevisiae.

Lanosterol metabolism was eleveted in yeast cells cultured both aerobically and semi-anaerobically by increased expression of lanosterol 14α-demethylase P450 (P450 14DM or CYP51). However, despite increases in the diene-intermediates of ergosterol biosynthesis, the ergosterol content was not affected. These results suggested that the levels of cellular sterols are controlled in at least tow stages, and that the concomitant elevation of P450 14DM and ergostadienols desaturase (P450 22DS ) is required to increase the cellular ergosterol content.

Purpose To evaluate restoration of the photoreceptor outer segment and visual outcomes in closed macular holes. Design Retrospective case series. Methods We retrospectively observed the reparative process of macular holes in 28 eyes one, three, and six months postoperatively using spectral-domain optical coherence tomography. We evaluated the reflective line at the junction between the photoreceptor inner and outer segment (IS/OS) and the best-corrected visual acuity (BCVA). Results The outer photoreceptor layer showed a foveal detachment, a disrupted IS/OS line, or both one month postoperatively. No eye had a continuous IS/OS line. These abnormalities were gradually restored at various levels. At six months, nine eyes had a normal outer photoreceptor layer, four eyes outer foveal defects with a continuous IS/OS line, 12 eyes a disrupted IS/OS line, and three eyes outer foveal defects with a disrupted IS/OS line. The mean BCVAs were significantly ( P = .017) lower in groups with a disrupted IS/OS line compared to groups with a continuous IS/OS line with or without outer foveal defects. Conclusions Macular hole closure is attained by bridge formation (foveal detachment) and the IS/OS line heals in varying degrees. The visual outcomes were significantly better in eyes with a continuous IS/OS line than in those with a disrupted IS/OS line.