The Effects of the Use of Diluted Bupivacaine in Sequential Combined Spinal and Epidural Anesthesia for Cesarean Delivery on Maternal Hypotension and Motor Block after Surgery: A Retrospective Observational Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p>0.99). 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. CONCLUSION: 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.

Nicotinamide phosphoribosyltransferase is a molecular target of potent anticancer agents identified from phenotype-based drug screening.

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.

Perioperative Administration of an Intravenous Beta-Blocker Landiolol Hydrochloride in Patients with Lung Cancer: A Japanese Retrospective Exploratory Clinical Study.

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.

Role of beta-oxidation in jasmonate biosynthesis and systemic wound signaling in tomato.

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 beta-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 beta-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.