Electromagnetic Simulation for THz Antenna-Coupled Microbolometers Operated at Room Temperature

Room-temperature terahertz (THz) detectors with higher performance are necessary for utilizing the THz wave in various sensing, spectroscopy and imaging, but even the best ones in the present are still insufficient for the practical applications. This issue is essential especially in the region around 1 THz at which there exists a large technology gap between microwave and middle-infrared. Therefore, we study to develop an antenna-coupled microbolometer to achieve a high-performance THz detector operated at a room-temperature for sensing at around 1 THz frequency wave. In this paper, we present several important features and results obtained from electromagnetic simulations, which help to design a structure of the antenna and heater to absorb efficiently the power of THz wave

Electromagnetic Simulation for THz Antenna-Coupled Microbolometers Operated at Room Temperature

Room-temperature terahertz (THz) detectors with higher performance are necessary for utilizing the THz wave in various sensing, spectroscopy and imaging, but even the best ones in the present are still insufficient for the practical applications. This issue is essential especially in the region around 1 THz at which there exists a large technology gap between microwave and middle-infrared. Therefore, we study to develop an antenna-coupled microbolometer to achieve a high-performance THz detector operated at a room-temperature for sensing at around 1 THz frequency wave. In this paper, we present several important features and results obtained from electromagnetic simulations, which help to design a structure of the antenna and heater to absorb efficiently the power of THz wave.Keywords: detector, dipole antenna, electromagnetic simulation, microbolometer, terahertz (THz

SGLT2阻害薬であるイプラグリフロジンは2型糖尿病自然発症モデルであるOLETFラットにおいて肝線維化進展を抑制する。

BACKGROUND: It is widely understood that insulin resistance (IR) critically correlates with the development of liver fibrosis in several types of chronic liver injuries. Several experiments have proved that anti-IR treatment can alleviate liver fibrosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules, improving IR. The aim of this study was to elucidate the effect of an SGLT2 inhibitor on the development of liver fibrosis using obese diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and their littermate nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. METHODS: Male OLETF and LETO rats were intraperitoneally injected with porcine serum twice a week for 12 weeks to augment liver fibrogenesis. Different concentrations of ipragliflozin (3 and 6 mg/kg) were orally administered during the experimental period. Serological and histological data were examined at the end of the experimental period. The direct effect of ipragliflozin on the proliferation of a human hepatic stellate cell (HSC) line, LX-2, was also evaluated in vitro. RESULTS: OLETF rats, but not LETO rats, received 12 weeks of porcine serum injection to induce severe fibrosis. Treatment with ipragliflozin markedly attenuated the development of liver fibrosis and expression of hepatic fibrosis markers, such as alpha smooth muscle actin, collagen 1A1, and transforming growth factor beta (TGF-β), and improved IR in a dose-dependent manner in OLETF rats. In contrast, the proliferation of LX-2 in vitro was not affected, suggesting that ipragliflozin had no significant direct effect on the proliferation of HSCs. CONCLUSION: In conclusion, our dataset suggests that an SGLT2 inhibitor could alleviate the development of liver fibrosis by improving IR in naturally diabetic rats. This may provide the basis for creating new therapeutic strategies for chronic liver injuries with IR.博士（医学）・甲第665号・平成29年3月15日© Japanese Society of Gastroenterology 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s00535-016-1200-6

アンジオテンシン受容体拮抗薬は、肝硬変ラットの骨格筋萎縮に対して、分岐鎖アミノ酸製剤による保護効果を増強する。

Scope: This study investigated the combined effect of the angiotensin II (AT-II) receptor blocker losartan and branched-chain amino acids (BCAAs) on skeletal muscle atrophy in rats with cirrhosis and steatohepatitis. Method and Results: Fischer 344 rats are fed a choline-deficient l-amino acid-defined (CDAA) diet for 12 weeks and treated with oral losartan (30 mg kg−1 day−1) and/or BCAAs (Aminoleban EN, 2500 mg kg−1 day−1). Treatment with losartan and BCAAs attenuated hepatic inflammation and fibrosis and improved skeletal muscle atrophy and strength in CDAA-fed rats. Both agents reduced intramuscular myostatin and pro-inflammatory cytokine levels, resulting in inhibition of the ubiquitin–proteasome system (UPS) through interference with the SMAD and nuclear factor-kappa B pathways, respectively. Losartan also augmented the BCAA-mediated increase of skeletal muscle mass by promoting insulin growth factor-I production and mitochondrial biogenesis. Moreover, losartan decreased the intramuscular expression of transcription factor EB (TFEB), a transcriptional inducer of E3 ubiquitin ligase regulated by AT-II. In vitro assays illustrated that losartan promoted mitochondrial biogenesis and reduced TFEB expression in AT-II-stimulated rat myocytes, thereby potentiating the inhibitory effects of BCAAs on the UPS and caspase-3 cleavage. Conclusion: These results indicate that this regimen could serve as a novel treatment for patients with sarcopenia and liver cirrhosis.博士（医学）・甲第861号・令和5年3月15

蛋白漏出性胃腸症における111In－トランスフェリン腹部イメージングの有用性

金沢大学大学院医学系研究

酢酸亜鉛とリファキシミンの併用療法による腸管バリアー機能維持によるエタノール誘発性肝線維化予防効果

BACKGROUND Hepatic overload of gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease (ALD) by inducing oxidative stress and activating Kupffer cells and hepatic stellate cells through toll-like receptor 4 signaling. Therefore, targeting the maintenance of intestinal barrier integrity has attracted attention for the treatment of ALD. Zinc acetate and rifaximin, which is a nonabsorbable antibiotic, had been clinically used for patients with cirrhosis, particularly those with hepatic encephalopathy, and had been known to improve intestinal barrier dysfunction. However, only few studies focused on their efficacies in preventing the ALD-related fibrosis development. AIM To investigate the effects of a combined zinc acetate with rifaximin on liver fibrosis in a mouse ALD model. METHODS To induce ALD-related liver fibrosis, female C57BL/6J mice were fed a 2.5% (v/v) ethanol-containing Lieber-DeCarli liquid diet and received intraperitoneal carbon tetrachloride (CCl4) injection twice weekly (1 mL/kg) for 8 wk. Zinc acetate (100 mg/L) and/or rifaximin (100 mg/L) were orally administered during experimental period. Hepatic steatosis, inflammation and fibrosis as well as intestinal barrier function were evaluated by histological and molecular analyses. Moreover, the direct effects of both agents on Caco-2 barrier function were assessed by in vitro assays.RESULTSIn the ethanol plus CCl4-treated mice, combination of zinc acetate and rifaximin attenuated oxidative lipid peroxidation with downregulation of Nox2 and Nox4. This combination significantly inhibited the Kupffer cells expansion and the proinflammatory response with blunted hepatic exposure of lipopolysaccharide and the toll-like receptor 4/nuclear factor kB pathway. Consequently, liver fibrosis and hepatic stellate cells activation were efficiently suppressed with downregulation of Mmp-2, -9, -13, and Timp1. Both agents improved the atrophic changes and permeability in the ileum, with restoration of tight junction proteins (TJPs) by decreasing the expressions of tumor necrosis factor α and myosin light chain kinase. In the in vitro assay, both agents directly reinforced ethanol or lipopolysaccharide-stimulated paracellular permeability and upregulated TJPs in Caco-2 cells. CONCLUSION Dual therapy with zinc acetate and rifaximin may serve as a strategy to prevent ALD-related fibrosis by maintaining intestinal barrier integrity.博士（医学）・甲第862号・令和5年3月15

カブトプリル投与中の分腎機能変化-腎血管性高血圧における診断的意義-

金沢大学大学院医学系研究

リファキシミンは腸-肝臓-筋肉軸の調節により肝硬変ラットの骨格筋萎縮に対するL-カルニチンを介した予防効果を増強する

The gut‑liver‑muscle axis is associated with the development of sarcopenia in liver cirrhosis. The present study aimed to illustrate the combined effects of rifaximin and L‑carnitine on skeletal muscle atrophy in cirrhotic rats with steatohepatitis. For this purpose, a total of 344 Fischer rats were fed a choline‑deficient L‑amino acid‑defined (CD AA) diet with the daily oral administration of rifaximin (100 mg/kg) and/or L‑carnitine (200 mg/kg), and measurements of psoas muscle mass index and forelimb grip strength were performed. After feeding for 12 weeks, blood samples, and liver, ileum and gastrocnemius muscle tissues were harvested. The effects of L‑carnitine on rat myocytes were assessed using in vitro assays. Treatment with rifaximin attenuated hyperammonemia and liver fibrosis in the CD AA‑fed rats. Moreover, it improved intestinal permeability with the restoration of tight junction proteins and suppressed the lipopolysaccharide (LPS)‑mediated hepatic macrophage activation and pro‑inflammatory response. In addition, rifaximin prevented skeletal muscle mass atrophy and weakness by decreasing intramuscular myostatin and pro‑inflammatory cytokine levels. Moreover, rifaximin synergistically enhanced the L‑carnitine‑mediated improvement of skeletal muscle wasting by promoting the production of insulin‑like growth factor‑1 and mitochondrial biogenesis, resulting in the inhibition of the ubiquitin‑proteasome system (UPS). The in vitro assays revealed that L‑carnitine directly attenuated the impairment of mitochondrial biogenesis, thereby inhibiting the UPS in rat myocytes that were stimulated with LPS or tumor necrosis factor‑α. On the whole, the present study demonstrates that the combination of rifaximin with L‑carnitine may provide a clinical benefit for liver cirrhosis‑related sarcopenia.博士（医学）・甲第863号・令和5年3月15

99mTc-tetrofosmin uptake in bone metastases from breast cancer

金沢大学大学院医学系研究