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Maternal hypotension is a common hemodynamic consequence of spinal anesthesia during cesarean delivery, but low-dose spinal anesthesia (9 mg bupivacaine) ensures stable hemodynamics and reduces motor block. The purpose of this retrospective observational study was to examine the effects of baricity of intrathecal administration of diluted bupivacaine in combined spinal-epidural anesthesia (CSEA) for cesarean delivery on maternal hypotension and motor block after surgery.The anesthesia and nursing records of 35 patients who had given birth by cesarean delivery under CSEA with intrathecal administration of plain or hyperbaric bupivacaine diluted in cerebrospinal fluid were reviewed. All patients were assigned to who received hyperbaric bupivacaine (hyperbaric group) or plain bupivacaine (plain group). Definition of feasibility of cesarean delivery by diluted low dose bupivacaine was set as no requirement of epidural administration of levobupivacaine during surgery. The incidences of hypotension (nadir blood pressure less than 80% of preanesthetic value) and motor block were reviewed.In 24 of the patients (68%), no additional epidural anesthesia was needed during surgery. One patient (3%) required additional epidural anesthesia before delivery. Feasibility of cesarean delivery was not different between hyperbaric group and plain group (p0.99). Eighteen of the patients (51%) did not require vasopressors, while 17 (49%) developed hypotension. There was no difference in incidence of maternal hypotension between hyperbaric and plain group. Only 6 patients (17%) required more than 3 times of administration of vasopressors among all patients. Modified Bromage scale scores were recorded in 28 of the patients (80%); scores of 0 (no motor block) were recorded in seven of them, and 1 in eight of them.Low-dose either plain or hyperbaric bupivacaine diluted in cerebrospinal fluid to approximately twice the volume may provide sufficient analgesia, fast motor recovery. Incidence of maternal hypotension was similar in hyperbaric and plain group.

Phenotypic screening in drug discovery has been revived with the expectation of providing promising lead compounds and drug targets and improving the success rate of drug approval. However, target identification remains a major bottleneck in phenotype-based drug discovery. We identified the lead compounds K542 and K405 with a selective inhibition of cell viability against sphingosine-1-phosphate lyase 1 (SGPL1)-transduced ES-2 cells by phenotypic screening. We therefore performed an in vivo pharmacological examination and observed the antitumor activity of K542 in an HT-1080 tumor-bearing mouse xenograft model. SGPL1 was expected to be a therapeutic target in some cancers, suggesting that these lead molecules might be promising candidates; however, their mechanisms of action still remain unexplained. We therefore synthesized the affinity probe Ind-tag derived from K542 and identified the proteins binding to Ind-tag via a pull-down experiment. Proteomics and biochemical analyses revealed that the target molecule of these lead compounds was Nicotinamide phosphoribosyltransferase (NAMPT). We established K542-resistant DLD-1 and HT-1080 cells, and genetic analyses of these cells identified a missense mutation in the NAMPT-encoding gene. This enzymatic experiment clearly showed that K393 exerts enzymatic inhibition against NAMPT. These proteomics, genetics and biochemical analyses clarified that compounds K542 and K405 were NAMPT inhibitors.

Beta-blockers have been reported to improve prognosis for various cancers, but the usefulness of perioperative administration remains unclear. To assess the efficacy of perioperative administration of landiolol hydrochloride, an intravenous beta-blocker, for lung cancer, we conducted a single-center, retrospective study. This study included patients who participated in a research conducted by Nippon Medical School Hospital from August 2012 to November 2013. The main selection criteria were males and females younger than 85 years old who have undergone anatomic lung resection for lung malignancies. Fifty-seven patients, 28 in the landiolol group and 29 in the control group, were included. The postoperative relapse-free survival rate at 2 years was 0.89 (95% CI, 0.78–1.01) in the landiolol group and 0.76 (95% CI, 0.60–0.91) in the control group (Chi-squared test; P = 0.1828). The relapse-free survival rate tended to be higher in the landiolol group than in the control. Hazard ratio for relapse-free survival in the landiolol group compared to the control was 0.41 (95% CI, 0.13–1.34), demonstrating that relapse free survival was prolonged in the landiolol group (log-rank test; P = 0.1294). It was suggested that relapse-free survival was prolonged when landiolol hydrochloride was administered from the induction to completion of anesthesia. Further studies are needed to confirm our findings.

Background and Objective: Atrial fibrillation is a common complication after lung resection. We sought to determine the relationship between low-dose landiolol only intraoperatively administration and the incidence of atrial fibrillation development in patients who did not have atrial fibrillation before undergoing lung resection. Methods: Forty-five patients undergoing lung resection (lobectomy or bilobectomy), as indicated for lung cancer at Nippon Medical Hospital, between August 2012 and September 2013. Two patients were excluded from the final analysis. Patients were given either intravenous landiolol (n = 22) or placebo (n = 21) during lobectomy or bilobectomy only intraoperatively. This is prospective, randomized, placebo-controlled study. Main Outcome Measures: The primary end point was the incidence of sustained atrial fibrillation (≥30 min). Results: Postoperative atrial fibrillation occurred in 1 (4.5%) of the 22 patients in the landiolol group and 6 (28.6%) of the 21 patients in the placebo group. No serious adverse effects such as bradycardia and hypotention secondary to landiolol were observed. Conclusion: Low-dose landiolol infusion intraoperatively reduced the incidence of clinically significant atrial fibrillation in patients undergoing pulmonary lobectomy.

BACKGROUND: / Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the 'once-a-day' intervention of a healthy lunch on various metabolic parameters. / / METHODS: / For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. / / RESULTS: / Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. / / CONCLUSIONS: / In summary, the 'once-a-day' intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition.

Background and Objective: Anesthesiologists need to be familiar with perioperative changes in blood volume (BV); however, there is no standard method for repeated evaluation of BV over a short interval of time. We evaluated BV in the operation room using repeatable estimation methods. Method: Eighty-five ASA physical status I-II patients scheduled to undergo endoscopic urosurgery using irrigation fluid under general anesthesia at Nippon Medical School Hospital were included in this study. Irrigation with 3% sorbitol in water was commenced after establishment of general anesthesia and volumetric fluid balance, which was defined as control water balance (WB). Hematocrit (Hct), colloid osmotic pressure (COP), total protein (TP) and albumin (Alb) were repeatedly determined before and during anesthesia. BV was calculated using Allen’s formula and the changes in Hct, COP, TP and Alb. Main Outcome Measures: The main outcome was the accuracy of measuring changes in BV (△BV) calculated using the four serum markers. WB and the estimated △BV calculated from Hct, COP, TP and Alb (△BV-Hct, △BV-COP, △BV-TP, and △BV-Alb) were analysed using Pearson’s correlation coefficient test and Bland-Altman analysis. Results: Sixty-five patients were excluded. In the remaining 20 patients, there was a significant correlation between WB and △BV-COP (R2 = 0.72; P △BV-TP (R2 = 0.59; P △BV-Alb (R2 = 0.57; P △BV-Hct (R2 = 0.06). Conclusion: △BV-COP, △BV-TP and △BV-Alb had correlation with WB. However, since COP can be measured repeatedly with simplified instruments under selected clinical circumstances, while TP and Alb cannot. COP is the most useful marker to measure △BV during perioperative period. Hct does not allow precise estimation of △BV.

Stereoselective installation of two side chains affords the key lactone (VI) in a 60% overall yield from monoacetate (I).

The RTX respirator is a biphasic external cuirass-style ventilator that supports both inspiration and expiration at various cycle rates and pressures, as well as allowing application of the vibration and cough modes. With this respirator, the duration and pressure can be altered in both the inspiratory and expiratory phases, and it can promote the removal of secretions by switching between the vibration mode (which involves external high-frequency oscillation: EHFO) and the cough mode. We used this respirator to remove secretions in two elderly patients with extensive atelectasis. They were nursed in the lateral decubitus position with the cuirass attached to one side of the chest only. The vibration mode removed secretion to reduce the viscosity of secretions and loosen impacted bronchial secretions. The cough mode interrupts the vibration mode and forces secretions towards the pharynx. The lateral decubitus position was useful for postural drainage. The extensive atelectasis of both patients was improved by this procedure. The RTX respirator may be a useful tool for the management of elderly patients with sputum retention.

CuCN-catalyzed reaction of the (1 R )-isomer of 4-cyclopentene-1,3-diol monoacetate with TBDPSO(CH 2 ) 6 MgCl produced an S N 2-type product regioselectively in high yield. Mitsunobu inversion of the product and subsequent Claisen rearrangement furnished aldehyde with the two side chains, from which the title compounds were synthesized efficiently.

Jasmonic acid (JA) and methyl jasmonate (MeJA), collectively known as JAs, regulate diverse physiological processes in plants, including the response to wounding. Recent reports suggest that a cyclopentenone precursor of JA, 12-oxo-phytodienoic acid (OPDA), can also induce gene expression. However, little is known about the physiological significance of OPDA-dependent gene expression. We used microarray analysis of approximately 21,500 Arabidopsis (Arabidopsis thaliana) genes to compare responses to JA, MeJA, and OPDA treatment. Although many genes responded identically to both OPDA and JAs, we identified a set of genes (OPDA-specific response genes [ORGs]) that specifically responded to OPDA but not to JAs. ORGs primarily encoded signaling components, transcription factors, and stress response-related genes. One-half of the ORGs were induced by wounding. Analysis using mutants deficient in the biosynthesis of JAs revealed that OPDA functions as a signaling molecule in the wounding response. Unlike signaling via JAs, OPDA signaling was CORONATINE INSENSITIVE 1 independent. These results indicate that an OPDA signaling pathway functions independently of JA/MeJA signaling and is required for the wounding response in Arabidopsis.

Δ 2 -OPC-8:0 (6), designed as a β-oxidation-insensitive analogue, was synthesized starting with 4-cyclopentene-1,3-diol monoacetate (5) in a stereocontrolled manner. The C(3)-C(8) moiety was first attached to the cyclopentene ring by using the Cu-catalyzed S N 2-type reaction with TBDPSO(CH 2 ) 6 MgCl and was later converted into the full side chain by Wittig reaction. In addition, OPC-6:0 (3) was synthesized.

Stereoselective installation of two side chains affords the key lactone (VI) in a 60% overall yield from monoacetate (I).

CuCN-catalyzed reaction of the (1 R )-isomer of 4-cyclopentene-1,3-diol monoacetate with TBDPSO(CH 2 ) 6 MgCl produced an S N 2-type product regioselectively in high yield. Mitsunobu inversion of the product and subsequent Claisen rearrangement furnished aldehyde with the two side chains, from which the title compounds were synthesized efficiently.

Jasmonic acid (JA) is a lipid-derived signal that regulates plant defense responses to biotic stress. Here, we report the characterization of a JA-deficient mutant of tomato (Lycopersicon esculentum) that lacks local and systemic expression of defensive proteinase inhibitors (PIs) in response to wounding. Map-based cloning studies demonstrated that this phenotype results from loss of function of an acyl-CoA oxidase (ACX1A) that catalyzes the first step in the peroxisomal β-oxidation stage of JA biosynthesis. Recombinant ACX1A exhibited a preference for C12 and C14 straight-chain acyl-CoAs and also was active in the metabolism of C18 cyclopentanoid-CoA precursors of JA. The overall growth, development, and reproduction of acx1 plants were similar to wild-type plants. However, the mutant was compromised in its defense against tobacco hornworm (Manduca sexta) attack. Grafting experiments showed that loss of ACX1A function disrupts the production of the transmissible signal for wound-induced PI expression but does not affect the recognition of this signal in undamaged responding leaves. We conclude that ACX1A is essential for the β-oxidation stage of JA biosynthesis and that JA or its derivatives is required both for antiherbivore resistance and the production of the systemic wound signal. These findings support a role for peroxisomes in the production of lipid-based signaling molecules that promote systemic defense responses.

Nine new pamamycin homologues were isolated from the culture broth of Streptomyces alboniger IFO 12738 using a combination of ODS and NH2 HPLCs, and their structures determined by GC-MS. The structural differences in these homologues are in the numbers and positions of methyl and ethyl groups. The aerial mycelium-inducing and growth-inhibitory activities in S. alboniger of these homologues and their antibiotic activity against Bacillus subtilis were examined. The effects of the alkyl substituents on these activities are discussed.