Effects of Volatile Anesthetics on Oral Tissue Blood Flow in Rabbits: A Comparison Among Isoflurane, Sevoflurane, and Desflurane.

PURPOSE: The aim of this study was to compare the concentration-dependent effects of isoflurane, sevoflurane, and desflurane on oral tissue blood flow. MATERIALS AND METHODS: Thirty male Japan White rabbits were randomized to receive 1 of 3 volatile anesthetics: isoflurane (group Iso), sevoflurane (group Sevo), or desflurane (group Des). The end-tidal concentration of each volatile anesthetic was regulated to 0.5, 1, and 1.5 minimum alveolar concentrations (MACs). The observed variables were heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, common carotid arterial blood flow, tongue mucosal blood flow, mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow, and lower alveolar tissue blood flow (LBF). RESULTS: The blood pressure in each group tended to decrease depending on the concentration of each volatile anesthetic, with the smallest effect in group Des. BBF and MBF in group Iso were higher than those in group Des at 1 MAC, and MBF and LBF in group Iso were highest at 1.5 MAC. CONCLUSION: The results of this study suggest that each volatile anesthetic produced unique effects on blood flow in oral tissues and circulatory parameters. Among the 3 volatile anesthetics, desflurane produced the smallest effects on oral tissue blood flow.

Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

PURPOSE: To determine whether continuous administration of nitrous oxide and remifentanil­either alone or together­alters blood flow in oral tissues during sevoflurane anesthesia. METHODS: Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 µg/kg/min remifentanil, and their combination) for 20 min. RESULTS: Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. CONCLUSIONS: Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

Bioconversion of small molecules by cytochrome P450 species expressed in Escherichia coli.

P450 (cytochrome P450) enzymes catalyse the mono-oxygenation of a wide range of compounds such as steroids, fatty acids, vitamins and drugs. In the present paper we demonstrate a system for bioconverting diverse compounds [flavanone, DHEA (dehydroepiandrosterone) and 7-ethoxycoumarin] using P450 species expressed in Escherichia coli. First, we expressed four P450 species: rabbit CYP2B (P450 family 2, subfamily B), fruitfly (Drosophila) CYP317A, rat CYP3A23 and mouse CYP2J5. Next, we added substrates directly to the incubation medium. The resulting metabolites were extracted and analysed by HPLC and spectrofluorimetry. The first substrate, 7-ethoxycoumarin, was de-ethylated by CYP2B; CYP2J5 and CYP3A23 showed weak activity, and CYP317A had no activity for 7-ethoxycoumarin. We next used flavanone, a flavonoid, as a substrate for these four P450 species and other P450 species expressed previously. As a result, CYP2B, CYP2C43 and CYP2C29 catalysed flavanone 2-hydroxylation. CYP2A5 catalysed 2- and 4-hydroxylations. Finally, to produce diverse modified compounds, variants of CYP2A5 with point mutations were incubated with a steroid (DHEA) and an antioxidant (flavanone) in vivo. HPLC analysis indicated that two P450 species produced a 7-beta-hydroxy-DHEA and two P450 species produced a 2-alpha-hydroxy-DHEA. Four P450 species catalysed flavanone 2- and 4-hydroxylations. These results indicate that bioconversion by P450 is a useful technique to modify small molecules (steroids, coumarin and flavanone) and produce new, diverse hydroxylated compounds, which could be used for high-throughput screening for drug discovery.

Bioconversion by functional P450 1A9 and P450 1C1 of Anguilla japonica.

We indicated that two P450s (1A9 and 1C1) from Japanese eel (Anguilla japonica) metabolized 7-ethoxycoumarin, 7-ethoxyresorufin, and flavanone. At first, we constructed expression vectors for two types of P450 (1A9 and 1C1). The reduced CO-difference spectra of Escherichia coli cells transformed with these plasmids showed Soret peaks (450 nm) that were typical of P450s. We performed bioconversion experiments in which substrates were added directly to incubation medium. The resulting metabolite(s) were extracted and analyzed by high-performance liquid chromatography and spectrofluorometer. Incubation of 50 nmol 7-ethoxyresorufin with P450 1C1 yielded 0.773 nmol of deethylated product, whereas 50 nmol 7-ethoxycoumarin resulted in 4.76 nmol. P450 1A9 metabolized 50 nmol of 7-ethoxyresorufin and 7-ethoxycoumarin to yield 6.54 and 20.9 nmol of deethylated product, respectively. Incubation of 50 nmol flavanone with P450 1C1 yielded 1.46 nmol and 0.69 nmol of products, whereas 50 nmol flavanone with P450 1A9 resulted in 1.10 nmol. In this system, 4'-hydroxy flavanones were formed by P450 1A9 and P450 1C1. P450 1A9 also metabolized 50 nmol of 17 beta-estradiol to yield 4.25 nmol of product. In this system, 2-hydroxy estradiol was formed by P450 1A9 using 17 beta-estradiol as a substrate. This study is the first to identify the substrates that P450 1C1 and 1A9 metabolize.

Design, fabrication, and evaluation of crystal-cored fibers for efficient second-harmonic generation based on Cerenkov-radiation-type phase matching.

A formulation for calculating the optical second-harmonic power based on the Cerenkov-radiation-type phase matching is derived for a crystal-cored fiber. The prerequisite condition for high efficiency is expressed by a simple relation by use of the refractive indices of a core crystal, a core radius, and a fundamental wavelength. An organic crystal-cored fiber is designed and practically fabricated by the guiding principle derived here. A blue second-harmonic wave of 1.4 mW is obtained from a 1-mm-long fiber by use of a 60-mW semiconductor laser, and the second-harmonic intensity agrees well with the prediction. Degradation of the organic core crystal caused by the generated blue wave is observed, and the lifetime of the device is evaluated.