Changes in the plasma protein-binding rate of remifentanil during cardiopulmonary bypass.

AIMS: Cardiopulmonary bypass (CPB) reduces the plasma protein-binding rate of some anaesthetics and can enhance their pharmacological effects by increasing the unbound drug fraction. However, whether these changes occur with remifentanil remains to be explored. We investigated the changes in the protein-binding rate of remifentanil during CPB compared with propofol. METHODS: Thirteen patients (≥18 years old) who were scheduled to undergo cardiovascular surgery with CPB were included. Arterial blood samples were collected to measure the plasma concentrations of remifentanil and propofol before CPB (T1), 30 (T2) and 60 (T3) minutes after the start of CPB, and 30 min after CPB discontinuation (T4). The samples were immediately centrifuged to separate the plasma after blood collection. Equilibrium dialysis was used to separate the unbound fraction. The remifentanil and propofol concentrations were measured by liquid chromatography-mass spectrometry. The protein-binding rate was calculated based on the total and unbound fraction of each drug. RESULTS: The remifentanil protein-binding rates at each time point were 27.9% ± 11.2% (T1), 13.5% ± 4.4% (T2), 14.0% ± 3.3% (T3) and 24.5% ± 6.9% (T4). The propofol protein-binding rates were 97.5% ± 0.7% (n = 4; T1), 95.8% ± 1.4% (T2), 95.3% ± 1.3% (T3) and 95.8% ± 1.1% (T4). The protein binding rates of both drugs decreased during CPB and reversed after CPB. The change in the unbound fraction was 1.2-fold for remifentanil and 1.7-1.9-fold for propofol. CONCLUSIONS: Unlike propofol, remifentanil might not demonstrate significantly enhanced pharmacological effects during CPB.

A Pediatric Epidural Catheter Fracture Suspected to Be Caused by a Glue.

A 65-day-old baby boy underwent the Kasai procedure under general and epidural anesthesia. The epidural catheter was inserted between the T11 and T12 vertebrae under general anesthesia, and secured with sterile tape, ethyl-2-cyanoacrylate glue, and film. Intra- and postoperative epidural analgesia was effective and there was no leakage around the insertion site. On the third day post-surgery, we tried to remove the catheter but discovered it was fractured 67mm from the tip. During the ultrasound examination, we observed a hyper-echoic structure located between the laminae of T11/T12. The pediatric orthopedic surgeon recommended removing the catheter to avoid long-term neurological sequelae of leaving the catheter, such as infection, fibrosis, migration, and irritation of neural tissues. It was surgically removed uneventfully on postoperative day 4. We requested the manufacturer to inspect the cross-section of the catheter under a microscope. The cross-section showed that 20% of the area had undergone tearing due to traction, while the remaining 80% was cracked. We also requested the manufacturer simulation after that. The same catheter, fixed on the polyolefin resin plate instead of skin with the same tape and glue, was easily fractured after three days. It is suspected that using ethyl-2-cyanoacrylate glue caused the catheter to fracture. When using glue containing ethyl-2-cyanoacrylate for pediatric epidural catheter fixation, special care is advised.

Presence of low-energy chlorophylls d in photosystem I trimer and monomer cores isolated from Acaryochloris sp. NBRC 102871.

Acaryochloris species belong to a special category of cyanobacteria possessing chlorophyll (Chl) d. One of the photosynthetic characteristics of Acaryochloris marina MBIC11017 is that the absorption spectra of photosystem I (PSI) showed almost no bands and shoulders of low-energy Chls d over 740 nm. In contrast, the absorption spectra of other Acaryochloris species showed a shoulder around 740 nm, suggesting that low-energy Chls d within PSI are diversified among Acaryochloris species. In this study, we purified PSI trimer and monomer cores from Acaryochloris sp. NBRC 102871 and examined their protein and pigment compositions and spectral properties. The protein bands and pigment compositions of the PSI trimer and monomer of NBRC102871 were virtually identical to those of MBIC11017. The absorption spectra of the NBRC102871 PSIs exhibited a shoulder around 740 nm, whereas the fluorescence spectra of PSI trimer and monomer displayed maximum peaks at 754 and 767 nm, respectively. These spectral properties were different from those of MBIC11017, indicating the presence of low-energy Chls d within the NBRC102871 PSIs. Moreover, we analyzed the NBRC102871 genome to identify amino acid sequences of PSI proteins and compared them with those of the A. marina MBIC11017 and MBIC10699 strains whose genomes are available. The results showed that some of the sequences in NBRC102871 were distinct from those in MBIC11017 and MBIC10699. These findings provide insights into the variety of low-energy Chls d with respect to the protein environments of PSI cores among the three Acaryochloris strains.

Association Between Early Hyponatremia and Clinical Outcomes in Critically Ill Patients: A Retrospective Cohort Study.

INTRODUCTION: Hyponatremia, frequently encountered in intensive care (ICU) settings, plays a critical role in shaping patient outcomes. Despite its prevalence, contemporary research into its newly classified severity categories and their implications on mortality, renal function, and length of stay remains limited. This study aims to fill this gap by examining the impact of hyponatremia severity on these critical outcomes. METHODS: A retrospective analysis of ICU patients aged >18 years who were admitted between March 2019 and December 2022 was conducted at Hamamatsu University Hospital, Shizuoka, Japan. Patients who were readmitted or had incomplete data were excluded. Hyponatremia was categorized as mild (130-135 mmol/L), moderate (125-129 mmol/L), or severe (<125 mmol/L), following the criteria set by the European Society of Intensive Care Medicine. This classification utilized the lowest sodium concentration within 24 hours of ICU admission. The outcomes were in-hospital mortality, ICU mortality, newly implemented renal replacement therapy (RRT), and length of hospital and ICU stay. Outcomes were analyzed using multivariable logistic and linear regression models, adjusting for relevant covariates including age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) III scores, and the use of mechanical ventilation. RESULTS: Of the 3,538 patients analyzed, 1,072 (30.3%) experienced hyponatremia: 894 (25.3%) mild, 144 (4.1%) moderate, and 34 (1.0%) severe. Multivariable analysis revealed no significant association between hyponatremia severity and in-hospital mortality rates across normonatremia (3.8%), mild (5.2%), moderate (11.8%), and severe (23.5%) groups, nor with ICU mortality. However, compared to normonatremia, moderate and severe hyponatremia were associated with increased RRT initiation (odds ratios = 3.83 and 6.36, respectively) and prolonged hospital stay (mean difference = 7.06 and 9.66 days, respectively), and ICU stays (mean difference, 1.02 and 2.70 days, respectively). Mild hyponatremia was not significantly associated with RRT or length of stay. CONCLUSION: Moderate-to-severe hyponatremia did not influence mortality but was associated with increased RRT initiation and prolonged hospital and ICU stay. By contrast, mild hyponatremia was not associated with any clinical outcome. Further research is required to determine if correcting hyponatremia directly improves ICU patient outcomes, given the observational nature of the study.

Predicted effect-site concentrations of remimazolam for i-gel insertion: a prospective randomized controlled study.

This study is the first to report 50% and 95% effect-site concentrations (EC50 and EC95, respectively) of the new short-acting benzodiazepine, remimazolam, for the successful insertion of i-gels with co-administration of fentanyl. Thirty patients (38 ± 5 years old, male/female = 4/26) were randomly assigned into five groups to receive one of five different remimazolam doses (0.1, 0.15, 0.2, 0.25, and 0.3 mg/kg bolus followed by infusion of 1, 1.5, 2, 2.5, and 3 mg/kg/h, respectively, for 10 min), which were designed to maintain a constant effect-site concentration of remimazolam at the time of i-gel insertion. At 6 min after the start of remimazolam infusion, all patients received 2 µg/kg fentanyl. i-gel insertion was attempted at 10 min and the success or failure of insertion were assessed by the patient response. Probit analysis was used to estimate the EC50 and EC95 values of remimazolam with 95% confidence intervals (CIs). In the five remimazolam dose groups, two, two, four, five, and six of the six patients in each group had an i-gel successfully inserted. Two patients in the lowest remimazolam dose group were conscious at the time of i-gel insertion and were counted as failures. The EC50 and EC95 values of remimazolam were 0.88 (95% CI, 0.65-1.11) and 1.57 (95% CI, 1.09-2.05) µg/ml, respectively. An effect-site concentration of ≥ 1.57 µg/ml was needed to insert an i-gel using remimazolam anesthesia, even with 2 µg/kg fentanyl. Trial registration: The study was registered in Japan Registry of Clinical Trials on 19 April 2021, Code jRCTs041210009.

The structure of PSI-LHCI from Cyanidium caldarium provides evolutionary insights into conservation and diversity of red-lineage LHCs.

Light-harvesting complexes (LHCs) are diversified among photosynthetic organisms, and the structure of the photosystem I-LHC (PSI-LHCI) supercomplex has been shown to be variable depending on the species of organisms. However, the structural and evolutionary correlations of red-lineage LHCs are unknown. Here, we determined a 1.92-Å resolution cryoelectron microscopic structure of a PSI-LHCI supercomplex isolated from the red alga Cyanidium caldarium RK-1 (NIES-2137), which is an important taxon in the Cyanidiophyceae. We subsequently investigated the correlations of PSI-LHCIs from different organisms through structural comparisons and phylogenetic analysis. The PSI-LHCI structure obtained shows five LHCI subunits surrounding a PSI-monomer core. The five LHCIs are composed of two Lhcr1s, two Lhcr2s, and one Lhcr3. Phylogenetic analysis of LHCs bound to PSI in the red-lineage algae showed clear orthology of LHCs between C. caldarium and Cyanidioschyzon merolae, whereas no orthologous relationships were found between C. caldarium Lhcr1-3 and LHCs in other red-lineage PSI-LHCI structures. These findings provide evolutionary insights into conservation and diversity of red-lineage LHCs associated with PSI.

Oxygen-evolving photosystem II structures during S1-S2-S3 transitions.

Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0-4) at the Mn4CaO5 cluster1-3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4-7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O-O bond formation.