Prediction of blood pressure changes during surgical incision using the minimum evoked current of vascular stiffness value under sevoflurane anesthesia.

Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = - 0.735 (P < 0.01), similar to that in a previous study with propofol (R = - 0.723). Thus, a high correlation was observed. The slope of the linear regression equation was - 0.27, similar to that obtained in the study on propofol (- 0.28). These results suggest that, as with propofol anesthesia, MECK can be used as a predictive index for ROCBP under 0.7 MAC sevoflurane anesthesia.Clinical trial registration: Registry, University hospital Medical Information Network; registration number, UMIN000047425; principal investigator's name, Noboru Saeki; date of registration, April 8, 2022.

Levonorgestrel causes feminization and dose-dependent masculinization in medaka fish (Oryzias latipes): Endocrine-disruption activity and its correlation with sex reversal.

The effect of a synthetic progestin, levonorgestrel (LNG), on the sex of exposed embryos was examined in medaka fish (Oryzias latipes). The aims of this study are to clarify the dual effect of LNG on sex and the correlation with its androgenic/estrogenic potential in medaka. LNG exposure causes significant dose-dependent masculinization (0.1-100 µg/L), whereas a decrease in the masculinization ratio is observed at 100 µg/L. LNG also causes significant feminization at 1-100 µg/L, but not in a dose-dependent manner. Exposure of estrogen-responsive gene (choriogeninH-EGFP) transgenic embryos to 100 µg/L LNG produced significant fluorescent signals in hatched fry. In vitro transcriptional assays indicated that LNG at 10-7-10-5 M induced significant activity for estrogen receptor (ESR)2a and ESR2b, but not for ESR1. In pre-self-feeding fry at 5 days post hatching (dph), 1-100 µg/L LNG caused a significant increase in the mRNA of choriogeninH, irrespective of genetic sex. Moreover, LNG (10-10-10-5 M) also caused a significant increase in the transcriptional activity of androgen receptor (AR) α and ARß in vitro, and 0.1 µg/L LNG significantly increased the mRNA levels of a testis-differentiation initiation factor, gonadal soma-derived factor (gsdf), as an androgen-upregulated and estrogen-downregulated gene, in 5 dph XX fry to levels similar to those in the control XY fry. However, 100 and 10 µg/L LNG suppressed or did not induce gsdf mRNA expression in XY and XX fry, respectively. Together, these findings show that LNG exerts estrogenic and androgenic activities in different concentration ranges, which correlate with the ratio of LNG-induced sex reversal. These results suggest for the first time, that medaka exposure to LNG can induce masculinization and feminization, based on the balance between androgenic and estrogenic activities, and the protocol applied in this study represents an alternative to the traditional animal model used to screen for endocrine-disrupting potential.

Preself-Feeding Medaka Fry Provides a Suitable Screening System for in Vivo Assessment of Thyroid Hormone-Disrupting Potential.

Endocrine-disrupting chemicals are assessed based on their physiological potential and their potential associated adverse effects. However, suitable end points for detection of chemicals that interfere with the thyroid hormone (TH) system have not been established in nonmammals, with the exception of amphibian metamorphosis. The aims of the current study were to develop an in vivo screening system using preself-feeding medaka fry (Oryzias latipes) for the detection of TH-disrupting chemicals and elucidate the underlying molecular mechanism. 17α-Ethinylestradiol (EE2: <100 ng/L) did not induce mRNA expression of estrogen-responsive genes, vitellogenins (vtgs) mRNA. Meanwhile, coexposure with thyroxin (T4) induced an increase of vtg expression. TH-disrupting chemicals (thiourea (TU), perfluorooctanoic acid (PFOA), and tetrabromobisphenol A (TBBPA)) significantly suppressed EE2 (1,000 ng/L)-induced vtg1 expression, while T4 rescued their expression as well as that of thyroid hormone receptor α (tRα) and estrogen receptors (esrs). These results were supported by in silico analysis of the 5'-transcriptional regulatory region of these genes. Furthermore, the esr1 null mutant revealed that EE2-induced vtg1 expression requires mainly esr2a and esr2b in a TH-dependent manner in preself-feeding fry. Application of preself-feeding medaka fry as a screening system might help decipher the in vivo mechanisms of action of TH-disrupting molecules, while providing an alternative to the traditional animal model.

Pre-Analytical Modification of Serum miRNAs: Diagnostic Reliability of Serum miRNAs in Hemolytic Diseases.

Circulating microRNAs (miRNAs) are useful biomarkers of hemolysis. Since blood cells are the main origins of circulating miRNAs, we evaluated blood cell-related pre-analytical modification of the miRNA signatures during blood drawing and serum processing. The levels of miRNA before and after ex vivo blood drawing were analyzed with the reverse transcriptase-based polymerase chain reaction method. Furthermore, the changes of miRNA signatures caused by different time-lag between blood drawing and serum preparation by 24 h were evaluated. Finally, we compared the miRNA levels between leftover samples and samples of hemolytic diseases. Blood drawing procedure induced increments of red blood cell (RBC)-related miRNAs (miR-451a, miR-486) about 2-fold. One hour standing of blood samples before serum separation induced almost the same increases in RBC-related miRNAs. To test the clinical usefulness of miR-451a as a biomarker of hemolytic diseases, we analyzed miRNAs of samples from 10 normal subjects, 30 leftover samples in the clinical laboratory, and 20 samples from patients with hemolytic diseases. Serum miR-451a significantly increased in patients with hemolytic anemia more than the levels of pre-analytical modification. In conclusion, the pre-analytical modification of serum miRNAs did not disturb the usefulness of RBC-derived miRNAs as biomarkers of hemolytic diseases.