Cytotoxic evaluation of natural and synthetic callipeltins: a revision of cytotoxicity of callipeltin B

<p>The cytotoxic evaluation of natural and synthetic callipeltins is described. Cyclic depsipeptide callipeltin B and linear peptides callipeltins E and M synthesized by us showed no cytotoxic activity. In contrast, natural callipeltin B purified from <i>Callipelta</i> sp. showed CC₅₀ = 130 μM against Hela cells. We found that purified callipeltin B included the contamination of callipeltins C and H at a ratio of approximately 15%. These results suggested that the cytotoxicity of natural callipeltin B was derived from callipeltins C and H.</p

Total Synthesis of Callipeltin B and M, Peptidyl Marine Natural Products

Total synthesis of callipeltins B and M, peptidyl cytotoxic agents isolated from marine sponges, by the combination of Fmoc solid-phase peptide synthesis and cyclization and global deprotection in the solution phase is described. Eight amino acids, including several unusual amino acids, were assembled on a solid support, and effective TFA-mediated deprotection was employed to reach callipeltin M. Callipeltin B was accomplished via the macro­lactonization between the side chain of d-<i>a</i>Thr and the C-terminus carboxylic acid of protected callipeltin M

Ralstonins A and B, Lipopeptides with Chlamydospore-Inducing and Phytotoxic Activities from the Plant Pathogen <i>Ralstonia solanacearum</i>

<i>Ralstonia solanacearum</i> has an orphan hybrid polyketide synthase-nonribosomal peptide synthetase gene cluster. We herein isolate its products (named ralstonins A and B) from <i>R. solanacearum</i> and elucidate their structures and biological activities. Ralstonins are unusual lipodepsipeptides composed of 11 amino acids (containing unique amino acids such as β-hydroxytyrosine and dehydroalanine) and a 3-amino-2-hydroxyoctadecanoic acid, and their production is controlled by quorum sensing, a mechanism of bacterial cell–cell communication. Ralstonins exhibited chlamydospore-inducing activity and phytotoxicity

Association between institutional procedural preference and in-hospital outcomes in laparoscopic surgeries; Insights from a retrospective cohort analysis of a nationwide surgical database in Japan

<div><p>Objective</p><p>To assess the use of laparoscopic surgeries (LS) and the association between its performance and hospitals’ preference for LS over open surgeries.</p><p>Summary background data</p><p>LS is increasingly used in many abdominal surgeries, albeit both with and without solid guideline recommendations. To date, the hospitals’ preference (LS vs. open surgeries) and its association with in-hospital outcomes has not been evaluated.</p><p>Methods</p><p>We enrolled patients undergoing 8 types of gastrointestinal surgeries in 2011–2013 in the Japanese National Clinical Database. We assessed the use of LS and the occurrences of surgery-related morbidity and mortality during the study period. Further, for 4 typical LS procedures, we assessed the hospitals’ preference for LS by modeling the propensity to perform LS (over open surgeries) from patient-level factors, and estimating each institution’s observed/expected (O/E) ratio for LS use. Institutions with O/E>2 were defined as LS-dominant. Using hierarchical logistic regression models, we assessed the association between LS preference and in-hospital outcomes.</p><p>Results</p><p>Among 1,377,118 patients undergoing gastrointestinal procedures in 2,336 participating hospitals, use of LS increased in all 8 procedures (35.1% to 44.7% for distal gastrectomy (DG), and 27.5% to 43.2% for right hemi colectomy (RHC)). Those operated at LS-dominant hospitals were at an increased risk of operative death (OR 1.83 [95%CI, 1.37–2.45] for DG, 1.79 [95%CI, 1.43–2.25] for RHC) compared to standard O/E level hospitals (0.5≤O/E<2.0).</p><p>Conclusions</p><p>LS use widely increased during 2011–2013 in Japan. Facilities with higher than expected LS use had higher mortality compared to other hospitals, suggesting a need for careful patient selection and dissemination of the procedure.</p></div

Proportion of LS among all surgeries by surgical procedure type over time.

<p>Q, quarter.</p

Descriptive statistics over time for total surgical procedure.

<p>Descriptive statistics over time for total surgical procedure.</p

Relationship between annual procedure volume vs. observed/expected operative mortality ratio for all surgeries and for LS by procedure.

<p>O/E, observed/expected.</p

Subgroups analyses for relative odds of surgical mortality in LS dominant hospital (O/E ≥2) compared to standard LS preference hospitals (0.5≤O/E<2) by surgical type (LS vs. OS) and by hospital volume.

<p>Subgroups analyses for relative odds of surgical mortality in LS dominant hospital (O/E ≥2) compared to standard LS preference hospitals (0.5≤O/E<2) by surgical type (LS vs. OS) and by hospital volume.</p

Descriptive statistics for each treatment indication hospital group.

<p>Descriptive statistics for each treatment indication hospital group.</p

Models for LS propensity in each surgical procedure.

<p>Models for LS propensity in each surgical procedure.</p