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Regional cerebral oxygen saturation (rSO.sub.2) measured using near-infrared spectroscopy has been reported to be significantly lower in hemodialysis (HD) patients than in non-HD ones, but the mechanisms are unknown. The aim of this prospective study was to assess the accuracy of near-infrared spectroscopy to estimate cerebral oxygenation in HD patients undergoing cardiovascular surgery. Our hypothesis was that rSO.sub.2 values would underestimate cerebral oxygenation in HD patients. This study included 113 patients (7 HD patients and 106 non-HD ones) undergoing cardiac or major aortic surgery between December 2015 and November 2017. We evaluated the validity of rSO.sub.2 by comparing it with ipsilateral jugular venous oxygen saturation (SjvO.sub.2). In HD and non-HD patients, rSO.sub.2 and SjvO.sub.2 showed a weak correlation (R.sup.2: 0.46 and 0.28 in HD and non-HD patients, respectively). Bland-Altman analysis revealed that bias (95% limits of agreement) of rSO.sub.2 compared to SjvO.sub.2 was - 19.2% ( - 41.7-3.3%) in HD patients and - 1.9% (- 19.3-15.5%) in non-HD ones. The large negative bias suggests that the rSO.sub.2 values measured using near-infrared spectroscopy substantially underestimate cerebral oxygenation in HD patients., Author(s): Shino Matsukawa [sup.1] , Shinichi Kai [sup.1] , Toshiyuki Mizota [sup.1] Author Affiliations: (Aff1) 0000 0004 0531 2775, grid.411217.0, Department of Anesthesia, Kyoto University Hospital, , 54 Shogoin-Kawahara-Cho, Sakyo-Ku, [...]

Purpose Data on the incidence of, risk factors for, and association with outcomes of acute kidney injury (AKI) after pediatric liver transplantation are scarce. We conducted a retrospective cohort study to determine the incidence of AKI after pediatric liver transplantation. In addition, we examined risk factors for AKI and association of AKI with outcomes. Methods This study included 156 children aged between 3 months and 18 years undergoing liver transplantation at Kyoto University Hospital. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines based on serum creatinine and urine output. We used multivariable logistic regression with stepwise variable selection to identify independent risk factors for AKI. Results AKI occurred in 72 patients (46.2%); 34 (21.8%) had stage 1, 32 (20.5%) had stage 2, and 6 (3.8%) had stage 3 AKI. Factors independently associated with the development of AKI were increased preoperative total bilirubin level (adjusted odds ratio, 1.04 per 1 mg/dl; 95% confidence interval, 1.01-1.09; P = 0.026) and increased intraoperative blood loss (adjusted odds ratio, 1.03 per 10 ml/kg; 95% confidence interval, 1.00-1.06; P = 0.022). AKI was significantly associated with prolonged hospitalization (median, 61 vs. 46 days; P = 0.028). In-hospital mortality rate was 4.2% in patients with AKI and 3.6% in those without AKI (P = 1.000). Conclusion The incidence of AKI after pediatric liver transplantation was 46.2%. Increased preoperative total bilirubin level and increased intraoperative blood loss were independently associated with the development of AKI. AKI was associated with prolonged hospitalization., Author(s): Miho Hamada [sup.1] , Shino Matsukawa [sup.1] , Satoshi Shimizu [sup.1] , Shinichi Kai [sup.1] , Toshiyuki Mizota [sup.1] Author Affiliations: (1) Department of Anesthesia, Kyoto University Hospital, 0000 [...]

Functional dipeptides carnosine and anserine are abundant in muscle. We determined the effect of short‐term dietary histidine (His) content on muscle carnosine and anserine contents and meat quality of broilers. Three groups of 28‐day‐old female broilers were fed diets with His contents of 67%, 100%, or 150% of requirement for 10 days before market (His contents 0.21%, 0.32%, and 0.48%, respectively). The carnosine and anserine contents of 0‐h aged muscle significantly increased with dietary His content; in particular, the carnosine content was 162% higher in the His 0.48% group than in the His 0.32% group. The contents of both peptides also increased with dietary His content in 48‐h aged muscle, but carnosine was not detected in 0‐ and 48‐h aged muscle of the His 0.21% group. The drip loss, cooking loss, shear force, and pH of meat were not affected by the dietary His content. The 2‐thiobarbituric acid‐reactive substances contents of 24‐ and 48‐h aged muscles were lower in the His 0.48% group than in the other groups, and the a* and b* values were lower in the His 0.21% group. These results suggest that short‐term dietary His content affects imidazole dipeptide contents, antioxidative capacity, and color of broiler meat. [ABSTRACT FROM AUTHOR]

The transcription factor hypoxia-inducible factor-1 (HIF- 1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28-32[degrees]C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-l[alpha] protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% [O.sub.2] conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-l-dependent gene expressions induced under 10% [O.sub.2] atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1[alpha] neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings. hypoxia; ischemia doi:10.l152/ajpregu.00732.2009

Remdesivir, a prodrug of the nucleoside analog GS‐441524, plays a key role in the treatment of coronavirus disease 2019 (COVID‐19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID‐19 with special characteristics. In this study, we aimed to measure serum GS‐441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS‐441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd) of GS‐441524. A one‐compartment model described serum GS‐441524 concentration data. The CL and Vd of GS‐441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS‐441524 using retrospectively obtained serum GS‐441524 concentrations in Japanese patients with COVID‐19, which would be helpful for optimal individualized therapy of remdesivir. [ABSTRACT FROM AUTHOR]