ナファモスタットメシル酸塩の抗酸化作用により、リネゾリド代謝は抑制される

藤田医科大

Increased intrapharyngeal pressure with combined use of high-flow nasal cannula and a surgical face mask: a preliminary study

OBJECTIVES: Nasal high-flow (NHF) therapy provides continuous positive airway pressure (CPAP), flushes the anatomical dead space, and improves mucociliary clearance. CPAP is usually applied at a flow rate at or above an established threshold value with the mouth closed because it is hard to maintain it with an open mouth. We conducted a prospective study to validate our hypothesis that CPAP can be applied with the mouth open through a surgical face mask. METHODS: We inserted 12-Fr nasogastric tubes through the noses of 18 healthy individuals and fixed each tube within the pharynx to monitor the intrapharyngeal pressure. We monitored the pressure during the following two conditions: NHF oxygen with the mouth open (condition O) and NHF oxygen with the mouth open and wearing a surgical face mask (condition OM). We set the NHF rate at 40 L/min and the oxygen concentration at 21%, under all conditions. We measured the intrapharyngeal pressure five times during each inspiration and expiration, and calculated mean values. RESULTS: The mean expiratory intrapharyngeal pressure (median [interquartile range]) increased significantly from the baseline during conditions O (2.08 [1.58–4.02] cm H(2)O) and OM (3.35 [2.72–3.79] cm H(2)O). In addition, there was a significant difference in pressure between conditions O and OM (p=0.0263, Wilcoxon signed-rank test). CONCLUSIONS: In our healthy volunteers, the intrapharyngeal pressures increased during expiration with an open mouth while wearing a surgical face mask

Recombinant human thrombomodulin inhibits neutrophil extracellular trap formation in vitro

The aim of this study was to investigate the effects of recombinant human-soluble thrombomodulin (rTM) on lipopolysaccharide (LPS)-induced, platelet-dependent neutrophil extracellular trap (NET) formation (NETosis). Human peripheral blood neutrophils and platelets were co-incubated with or without LPS (0.2 μg/ml) in the presence and absence of rTM (2 μg/ml). NETosis was confirmed by immunostaining and confocal microscopy. In the absence of platelets, LPS did not induce NETosis in the neutrophils. NETosis, however, was induced by LPS when neutrophils were co-cultured with platelets (64 % of neutrophils). Notably, rTM was able to fully inhibit NETosis in neutrophils cultured with platelets and in the presence of LPS. rTM did not induce NETosis in this co-culture system (p < 0.01 versus LPS in the absence of rTM). These results show that rTM can suppress LPS-induced platelet-dependent NETosis in vitro

Chronic Muscle Weakness and Mitochondrial Dysfunction in the Absence of Sustained Atrophy in a Preclinical Sepsis Model

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed

Farnesyltransferase inhibitors prevent HIV protease inhibitor (lopinavir/ritonavir)-induced lipodystrophy and metabolic syndrome in mice

Highly active antiretroviral therapy (HAART) has successfully reduced the mortality rate of patients with human immune deficiency virus (HIV) and HIV protease inhibitors (HIV PIs) are key components of HAART. Complications of HAART, particularly those associated with HIV PIs including lipodystrophy and metabolic disturbance, have emerged as an important public health issue. No specific treatment is available to prevent and/or treat HIV PI-associated lipodystrophy and metabolic syndrome. The present study demonstrated that a relatively low-dose of farnesyltransferase inhibitor (FTI), tipifarnib (3 mg/kg/day, subcutaneous injection) and lonafarnib (5 mg/kg/day, subcutaneous injection), prevented the onset of lipodystrophy and metabolic syndrome induced by the combination of two HIV PIs, lopinavir (50 mg/kg/day, intraperitoneal injection) and ritonavir (12.5 mg/kg/day, intraperitoneal injection), in mice. Consistent with previous studies, treatment with lopinavir/ritonavir for 2 weeks decreased body weight, adipose tissue mass, levels of plasma adiponectin and leptin, and increased plasma levels of triglycerides, total cholesterol and insulin. Tipifarnib and lonafarnb prevented or ameliorated all of these alterations in the HIV PI-treated mice. These data identify FTIs as a novel potential strategy to prevent or treat HIV PI-associated lipodystrophy and metabolic syndrome in HIV-infected patients on HAART

Effects of recombinant human soluble thrombomodulin on neutrophil extracellular traps in the kidney of a mouse model of endotoxin shock

journal articl

Effect of multidisciplinary interventions in perioperative management center on duration of preoperative fasting: A single-center before-and-after study

OBJECTIVES: Our aims were to clarify the actual situation regarding preoperative fasting and determine whether multidisciplinary interventions in a perioperative management center shorten the duration of preoperative fasting. METHODS: The cohort of this before-and-after study comprised patients undergoing elective surgery aged 18 years or older who underwent general anesthesia at one of three stages: after starting a short preoperative fasting protocol (Group A), after the anesthesiologist started explaining the protocol (Group B), and after the start of the perioperative management center (Group C). Instructions on drinking clear fluids were given up to 2 h and 4 h before the start of elective surgery to the first patient on the list (on-time) and to the second and subsequent patients (on-call), respectively. Data were collected retrospectively in Groups A and B and prospectively in Group C. RESULTS: The study cohort comprised 89 patients in Group A (50 on-time, 39 on-call), 108 in Group B (65 on-time, 43 on-call), and 284 in Group C (182 on-time, 102 on-call). The difference between the instructed and last drinking time was significantly shorter in Group C than Group A (30 [10, 140] vs. 30 [10, 60] vs. 20 [0, 50] min, p=0.003). The duration of fasting was significantly shorter in Group C than Group B (243 [150, 395] vs. 213 [151, 323] vs. 180 [146, 280] min, p=0.01). CONCLUSIONS: Multidisciplinary interventions at the perioperative management center tended to reduce the duration of fasting, suggesting that this approach may contribute to improved compliance