Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors.

4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-coumaric, caffeic, and ferulic acids, and the regulatory position of 4CL in the phenylpropanoid pathway renders the enzyme an attractive target that controls the composition of phenylpropanoids in plants. In this study, we designed and synthesized mechanism-based inhibitors for 4CL in order to develop useful tools for the investigation of physiological functions of 4CL and chemical agents that modulate plant growth with the ultimate goal to produce plant biomass that exhibits features that are beneficial to humans. The acylsulfamide backbone of the inhibitors in this study was adopted as a mimic of the acyladenylate intermediates in the catalytic reaction of 4CL. These acylsulfamide inhibitors and the important synthetic intermediates were fully characterized using two-dimensional NMR spectroscopy. Five 4CL proteins with distinct substrate specificity from four plant species, i.e., Arabidopsis thaliana, Glycine max (soybean), Populus trichocarpa (poplar), and Petunia hybrida (petunia), were used to evaluate the inhibitory activity, and the half-maximum inhibitory concentration (IC50) of each acylsulfamide in the presence of 4-coumaric acid (100 µM) was determined as an index of inhibitory activity. The synthetic acylsulfamides used in this study inhibited the 4CLs with IC50 values ranging from 0.10 to 722 µM, and the IC50 values of the most potent inhibitors for each 4CL were 0.10-2.4 µM. The structure-activity relationship observed in this study revealed that both the presence and the structure of the acyl group of the synthetic inhibitors strongly affect the inhibitory activity, and indicates that 4CL recognizes the acylsulfamide inhibitors as acyladenylate mimics.

[Optimal catheter position for PreSep central venous oximetry catheter].

BACKGROUND & METHODS: To evaluate optimal catheter position for PreSep central venous oximetry catheter, we inserted the catheter through a sheath introducer with contamination shield and conducted its in vivo calibration in twenty-eight patients. In the event of calibration failure due to unstable signals, the catheter was advanced until calibration became possible. If SQI rose to 3 or 4 during surgery, we readjusted the catheter position to resume reliable monitoring. At the conclusion of surgery, the catheter position was checked radiologically and the distance between the catheter tip and the upper border of the clavicle was measured. RESULTS: In 70% of the patients, calibration was performed successfully when the catheter was inserted for 12-14 cm from the top of the groove between the sternal and clavicular heads of the sternocleidomastoid muscle, which led to positioning of the catheter tip 5-7 cm from the upper border of the clavicle. However, there was a considerable variation within the total patient sample and no definite correlation was found between catheter positions and patient's height. In 30% of the patient, readjustment of the catheter was required during surgery. CONCLUSIONS: Use of a sheath introducer with contamination shield seems to be useful for positioning the PreSep catheter.

Intraoperative cardiac assessment with transesophageal echocardiography for decision-making in cardiac anesthesia.

Transesophageal echocardiography is an invaluable hemodynamic monitoring modality. Extended and anatomically based evaluation of cardiac function with transesophageal echocardiography is essential to prompt and accurate decision-making in anesthetic management during cardiac surgery. Fractional shortening and fractional area changes are indices widely used to assess the global systolic performance of the left ventricle. Monitoring regional function using semi-quantitative scoring has been demonstrated to be a more sensitive indicator of myocardial ischemia. Assessment of left ventricular diastolic function should be performed in a systematic way, measuring transmitral flow, pulmonary venous flow, transmitral color M-mode flow propagation velocity, and mitral annulus tissue Doppler imaging. The unique anatomical features of the right ventricle make echocardiographic evaluation complicated and therefore less frequently employed. Right ventricular fractional area change, tricuspid annular plane systolic excursion, maximal systolic tricuspid annular velocity with tissue Doppler imaging, and myocardial performance index are indices successfully incorporated into intraoperative right ventricular assessment. Left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve may develop after cardiac procedures. Transesophageal echocardiography plays a central role in prevention as well as diagnosis of systolic anterior motion. Transesophageal echocardiography is extremely useful not only for detecting and locating intracardiac air, but also for guiding and evaluating the procedures to remove air. Air is likely to persist in the right and left superior pulmonary vein, left ventricular apex, left atrium, right coronary sinus of Valsalva, and ascending aorta. Accurate evaluation of cardiac function depends on performing TEE examination properly and obtaining optimal images.

[Ultrasound-guided sciatic nerve block in the popliteal fossa for the postoperative pain control after Achilles' tendon repair].

To assess the usefulness of ultrasound-guided sciatic nerve block in the popliteal fossa in the postoperative pain management after Achilles' tendon repair, we compared 15 patients managed by general anesthesia and sciatic nerve block (Group B) with 17 patients managed by general anesthesia alone (Group G). The time required for the nerve block was about 20 minutes on the average, and the success rate was 100%. No significant complication associated with the nerve block was observed. Fentanyl dosing for the postoperative analgesia was significantly smaller in the Group B. Although the postoperative analgesic requirement was comparable, the time to the first postoperative analgesic administration was significantly longer in the Group B. This retrospective study suggests that ultrasound-guided sciatic nerve block in the popliteal fossa provides safe and effective postoperative pain relief after Achilles' tendon repair.

[Bleeding from the optical module connection port of a pulmonary artery catheter].

A 91-year-old man underwent aortic valve replacement using a pulmonary artery catheter (PAC). Intraoperative hemodynamic monitoring with the PAC showed no abnormality except for bleeding from optical module connection port. In the intensive care unit, difficulty in withdrawing the PAC was noted. Surgical removal of the PAC was performed, revealing the PAC sutured to the right atrium. When bleeding from the PAC connection ports is noted, it is advisable to suspect that the PAC might have been sutured.

Hb Nishinomiya [Leu-Gly-inserted between codons 69(E13) and 70(E14) of beta]: a novel unstable hemoglobin with reduced oxygen affinity found in a patient with spherocytic hemolysis.

Substantially decreased oxygen saturation levels were incidentally detected by pulseoxymetry in a patient with spherocytic hemolysis who was undergoing laparoscopic splenectomy. Molecular analysis revealed that he was carrying hemoglobin (Hb) Nishinomiya, a novel Hb variant [Leu-Gly-inserted between codons 69(E13) and 70(E14) of beta]. Amino acid substitutions around positions 70-73(E13-17) of the beta chain are likely to change stability and oxygen affinity, as has been demonstrated in several Hb variants including Hb Seattle. The apparent substitution of the amino acid residues in the heme pocket of the beta chain explains the decreased stability and oxygen affinity of Hb Nishinomiya.