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Arief Rahadian Daiju Fukuda Hotimah Masdan Salim Shusuke Yagi Kenya Kusunose Hirotsugu Yamada Takeshi Soeki Masataka Sata 《Journal of atherosclerosis and thrombosis》2020,27(11):1141
Aim: Recent studies have demonstrated that selective sodium–glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism.Method: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE−/−) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed.Result: Canagliflozin decreased blood glucose (P < 0.001) and total cholesterol (P < 0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P < 0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P < 0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P < 0.05, both). Methylglyoxal also decreased the phosphorylation of eNOSSer1177 and Akt but increased the phosphorylation of eNOSThr495 and p38 MAPK in HUVECs.Conclusion: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE−/− mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms. 相似文献
997.
Shunsuke Yamada Yasuhiro Kawai Shoji Tsuneyoshi Hiroaki Tsujikawa Hokuto Arase Hisako Yoshida Kazuhiko Tsuruya Toshiaki Nakano Takanari Kitazono 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2020,24(1):72-80
Preserving residual kidney function (RKF) is important in the management of patients on peritoneal dialysis. However, few studies have examined the association between serum albumin level and the risk of RKF loss. We prospectively recruited 104 patients who began peritoneal dialysis treatment at our hospital between 2006 and 2016. The primary outcome was complete RKF loss, defined as urine volume < 100 mL/day. Serum albumin level at baseline was the main exposure. During a median observation period of 24 months, 33 patients developed RKF loss. A Cox proportional hazards model showed that hypoalbuminemia was associated with an increased risk of RKF, even after adjustments for potential confounding factors. Multivariable‐adjusted linear regression analysis also showed that hypoalbuminemia was associated with greater rates of decline in 24‐h urine volume and in renal Kt/V urea. Our findings suggest that hypoalbuminemia is associated with an increased risk of RKF loss in patients with peritoneal dialysis. 相似文献
998.
Seishi Aihara Shunsuke Yamada Satoru Shichijo Kento Fukumitsu Mika Kondo Yutaro Hirashima Hideaki Oka Taro Kamimura Atsumi Harada Toshiaki Nakano Kazuhiko Tsuruya Takanari Kitazono 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2020,24(1):34-41
Vascular access intervention therapy (VAIVT) is necessary to maintain vascular access in patients undergoing hemodialysis. VAIVT‐associated vasodilatation is painful. However, few reports have focused on effective pain relief at the time of VAIVT. The present study was performed to determine whether lidocaine‐propitocain cream, a eutectic mixture of local anesthetics (EMLA), effectively reduces VAIVT‐associated pain in patients undergoing hemodialysis. This placebo‐controlled, double‐blind, crossover study was conducted in a single center. Among 210 patients who underwent a total of 437 VAIVT procedures from August 2017 to June 2018, 30 patients were randomly allocated to either the EMLA–placebo arm or placebo–EMLA arm at the time of VAIVT. EMLA application significantly reduced the visual analog scale score compared with placebo (47.0 ± 21.1 vs. 68.6 ± 20.7 mm, respectively; P < 0.05). EMLA is a safe and effective treatment for relief of VAIVT‐associated pain in patients undergoing hemodialysis. 相似文献
999.
Junya Yamamoto Daigo Nakazawa Saori Nishio Yasunobu Ishikawa Minoru Makita Yoshihiro Kusunoki So Nagai Yuichiro Fujieda Masahiko Takahata Kanji Yamada Tsuyoshi Yamamura Akihiko Yotsukura Masanobu Saito Masaru Shimazaki Tatsuya Atsumi 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2020,24(2):146-153
Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH. 相似文献
1000.
Hidetomo Nakamoto Xue‐Qing Yu Suhnggwon Kim Hideki Origasa Hongguang Zheng Jianghua Chen Kwon Wook Joo Suchai Sritippayawan Qinkai Chen Hung‐Chun Chen Yoshiharu Tsubakihara Hirofumi Tamai Sang Heon Song Indralingam Vaithilingam Kang Wook Lee Kuo‐Hsiung Shu Stanley Hok‐King Lo Masanao Isono Hajimu Kurumatani Kiyonobu Okada Hiroyuki Kanoh Takashi Kiriyama Shunsuke Yamada Toshiro Fujita 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2020,24(1):42-55
TRK‐100STP, a sustained‐release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK‐100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double‐blind, placebo‐controlled study conducted at 160 sites in seven Asia‐Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK‐100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end‐stage renal disease. No significant differences were observed in composite endpoints between TRK‐100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK‐100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms. 相似文献