The steroidogenic activities and receptor-binding properties of angiotensin II and des-Asp1-angiotensin II were analyzed and compared with the metabolism of each peptide during incubation with isolated rat and canine adrenal glomerulosa cells. In isolated rat glomerulosa cells, equimolar concentrations of each peptide stimulated aldosterone production similarly over the first 20 min of incubation. However, at later times, the des-Asp1 heptapeptide was consistently less active, with one third the potency of the octapeptide at 40 min, and only one tenth that of the octapeptide after 120 min. In dog glomerulosa cells, the des-Asp1 heptapeptide was less rapidly inactivated and retained one third the potency of the octapeptide after 120 min of incubation. In each species, the maximum aldosterone response to the two peptides was similar at all time intervals studied up to 120 min. Also, no additivity between maximal concentrations of angiotensin II and des-Asp1-angiotensin II was observed. Assay of angiotensin II receptors with radioiodinated and tritiated peptides in rat glomerulosa cells and adrenal particles showed identical receptor concentration for each peptide, with somewhat lower affinity for the heptapeptide (Ka = 0.7 × 109 M-1 for the heptapeptide vs. 2.7 × 109 M-1 for angiotensin II). The metabolism of angiotensin in isolated glomerulosa cells was analyzed by thin layer chromatography and assay of peptides in the incubation medium. Extensive degradation of angiotensin II during incubation with rat cells was detected, with relatively little conversion to the 2–8 and 3–8 peptides. RIA of medium peptides showed decreases to 50% and 30% for angiotensin II and des-Asp1-angiotensin II at 40 min, and to 26% and 10% at 120 min, respectively. Similar results were derived with radioreceptor assay and bioassay by stimulation of aldosterone production in fresh glomerulosa cells. In contrast, metabolism of angiotensin during incubation with dog adrenal glomerulosa cells was less rapid, and both peptides were degraded at the same rate. Analysis of labeled peptides eluted from rat glomerulosa cells after in vivo or in vitro binding of [125I]iodoangiotensin II showed that more than 90% of the bound radioactivity was composed of the octapeptide. These studies have revealed extensive metabolism of angiotensin peptides by isolated rat glomerulosa cells, with more rapid degradation of des-Asp1-angiotensin II than of the native octapeptide. Such peptide metabolism contributes to the apparent discrepancy in biological potencies of angiotensin II and des-Asp1-angiotensin II on aldosterone production in isolated rat glomerulosa cells. It is also evident that angiotensin II acts upon rat and dog glomerulosa cells to evoke aldosterone production without prior conversion to the heptapeptide.
Background: Current AHA guidelines do not recommend routine use of Mechanical CPR devices due to the decline in CPR quality during their preparation and application. However, Manual chest compressions during transport can reduce CPR quality. In situations where maintaining high-quality CPR is challenging, Mechanical CPR devices are essential. We hypothesized that real-time feedback (RF) could help maintain the quality of Manual CPR before Mechanical CPR devices are activated. Objectives: To investigate the impact of RF on the quality of Manual CPR before the activation of Mechanical CPR devices. Methods: This retrospective observational study included OHCA cases where Mechanical CPR using the LUCAS 3® device was performed between May 2023 and February 2024. We compared chest compression quality parameters, including Depth Achievement Rate (≥5cm) (%), Depth (cm), Rate Achievement Rate (100-120/min) (%), Rate (/min), Longest Interruption (s), and Chest Compression Fraction (CCF) (%) during Manual chest compressions before the application of the Mechanical CPR device between two periods, using the ZOLL X Series® monitor. During the first 5 months, RF was not used, and EMS teams could not see RF data, but chest compression quality parameters were recorded. During the subsequent 5 months, RF was displayed, and the same parameters were recorded. Results: The results are summarized in the attached figure. There were 10 cases without RF and 37 with RF. The RF group showed significant improvements in depth achievement rate (≥5cm) and compression depth. The rate achievement rate (100-120/min) and compression rate were similar between groups. The longest interruption time was shorter in the RF group, and the CCF was higher, although these differences were not statistically significant. The median duration of Manual CPR before applying the Mechanical CPR device was longer in the RF group [382s, IQR 110-654] compared to the non-RF group [156s, IQR 67-283], p=0.065. Conclusions: RF significantly improved the depth achievement rate and compression depth during Manual CPR before applying Mechanical CPR devices. Trends towards shorter interruption times and higher CCF in the RF group suggest RF may help maintain CPR quality. However, the retrospective nature and limited sample size may affect the generalizability of the results.
A new Fe-based amorphous alloy exhibiting the glass transition and supercooled liquid region before crystallization was searched in the composition range of Fe63Co7Nd10−xZrxB20(x=0 to 6 at%). The amorphous alloys containing 4 to 6 at%Zr were found to exhibit the glass transition, followed by a supercooled liquid region. The crystallization from the supercooled liquid of the 4%Zr alloy occurred through three stages of Am→Am′+Fe3B→Am″+Fe3B+γ-Fe+Nd2Fe23B3+Fe2Zr+Fe3Zr→α-Fe+Fe2Zr+Fe3Zr+Nd2Fe14B+Fe2B+ZrB2. In the crystallized state, the 4% and 6%Zr alloys exhibited hard magnetic properties, i.e., saturation magnetization of 1.15 to 1.18 T, remanence of 0.75 to 0.76 T, coercive force of 30 to 58 kA/m and maximum energy product of 7.8 to 13 kJ/m3. The grain sizes of the α-Fe and Nd2Fe14B phases for the 4%Zr alloy subjected to optimum annealing were about 45 and 25 nm, respectively. The fine mixed structure was thought to reveal the hard magnetic properties by the exchange magnetic coupling mechanism even in the coexistent state with Fe2Zr, Fe3Zr, Fe2B and ZrB2. The appearance of the glass transition also implies that the 4%Zr and 6%Zr alloys have a high glass-forming ability leading to the formation of a bulk amorphous alloy. The finding that the amorphous alloys exhibited the glass transition in the as-quenched state and the hard magnetic properties in the crystallized state is important, because the direct production of a bulk hard magnetic alloy by a simple process is expected, such as the crystallization of the cast bulk amorphous alloy.
Sepsis leads to organ dysfunction. Acute kidney injury, a common type of organ dysfunction, is associated with a high mortality rate in patients with sepsis. Kidney replacement therapy can correct the metabolic, electrolyte, and fluid imbalances caused by acute kidney injury. While this therapy can improve outcomes, evidence of its beneficial effects is lacking. Herein, we review the indications for blood purification therapy, including kidney replacement therapy, and the current knowledge regarding acute kidney injury in terms of renal and non-renal indications. While renal indications have been well-documented, indications for blood purification therapy in sepsis (non-renal indications) remain controversial. Excessive inflammation is an important factor in the development of sepsis; blood purification therapy has been shown to reduce inflammatory mediators and improve hemodynamic instability. Given the pathophysiology of sepsis, blood purification therapy may decrease mortality rates in these patients. Further trials are needed in order to establish the effectiveness of blood purification therapy for sepsis.
A preliminary report from a global study showed that remdesivir, a nucleoside analog pro-drug that was originally developed as a therapeutic drug against Ebola virus, may exert clinical efficacy in cases of COVID-19, by shortening the time to recovery. We had the opportunity to use this new drug in the treatment of 7 COVID-19 patients with respiratory failure.
Ginsenoside Rb1 (gRb1) is a main ingredient of ginseng root, which has been prescribed to patients for thousands of years in Asian countries without apparent adverse effects. We investigated the protective effects of gRb1 against ischemic damage of the cochlea. Ischemic insult was loaded by occluding the bilateral vertebral arteries for 15min in a gerbil, which lacks posterior communicating arteries causing the cochlea to be nourished solely by the vertebral arteries. GRb1 was dissolved in isotonic saline. Then, 200μL of gRb1 solution (50μg/200μL) was injected into the left femoral vein 1h after inducing ischemia. Hearing was assessed by recording the auditory brainstem responses (ABR). Seven days after ischemia, the animal showed a 22.5dB increase in ABR threshold, 26.5% loss of the inner hair cells at the basal turn, and 19.3 cells/10000μm2 spiral ganglion cell density on average in 6 ears. In the Ischemia-gRb1 group, the ABR threshold increase was 14.2dB, inner hair cell loss was 8.6%, and the density of spiral ganglion cells was 25.8 cells/10000μm2. These findings suggest that gRb1 inhibited ischemic injury of the inner ear.
Out-of-hospital cardiac arrest (OHCA) is a life-threatening emergency that requires rapid and efficient intervention. Recently, several novel approaches have emerged and have been incorporated into resuscitation systems in some local areas of Japan. This review describes innovative resuscitation systems and highlights their strengths. First, we discuss the deployment of a physician-staffed ambulance, in which emergency physicians offer advanced resuscitation to patients with OHCA on site. In addition, we describe the experimental practice of extracorporeal membrane oxygenation (ECPR) in a prehospital setting. Second, we describe a physician-staffed helicopter, wherein a medical team provides advanced resuscitation at the scene. We also explain their initiative to provide early ECPR, even in remote areas. Finally, we provide an overview of the "hybrid ER" system which is a "one-fits-all" resuscitation bay equipped with computed tomography and fluoroscopy equipment. This system is expected to help swiftly identify and rule out irreversible causes of cardiac arrest, such as massive subarachnoid hemorrhage, and implement ECPR without delay. Although these revolutionary approaches may improve the outcomes of patients with OHCA, evidence of their effectiveness remains limited. In addition, it is crucial to ensure cost-effectiveness and sustainability. We will continue to work diligently to assess the effectiveness of these systems and focus on the development of cost-effective and sustainable systems.
