OBJECTIVES: Fluid volume optimization guided by stroke volume measurements reduces complications of colorectal and high-risk surgeries. We studied whether dehydration or a strong hemodynamic response to general anesthesia increases the probability of fluid responsiveness before surgery begins. METHODS: Cardiac output, stroke volume, central venous pressure and arterial pressures were measured in 111 patients before general anesthesia (baseline), after induction and stepwise after three bolus infusions of 3 ml/kg of 6% hydroxyethyl starch 130/0.4 (n = 86) or Ringer's lactate (n = 25). A subgroup of 30 patients who received starch were preloaded with 500 ml of Ringer's lactate. Blood volume changes were estimated from the hemoglobin concentration and dehydration was estimated from evidence of renal water conservation in urine samples. RESULTS: Induction of anesthesia decreased the stroke volume to 62% of baseline (mean); administration of fluids restored this value to 84% (starch) and 68% (Ringer's). The optimized stroke volume index was clustered around 35-40 ml/m2/beat. Additional fluid boluses increased the stroke volume by ≥10% (a sign of fluid responsiveness) in patients with dehydration, as suggested by a low cardiac index and central venous pressure at baseline and by high urinary osmolality, creatinine concentration and specific gravity. Preloading and the hemodynamic response to induction did not correlate with fluid responsiveness. The blood volume expanded 2.3 (starch) and 1.8 (Ringer's) times over the infused volume. CONCLUSIONS: Fluid volume optimization did not induce a hyperkinetic state but ameliorated the decrease in stroke volume caused by anesthesia. Dehydration, but not the hemodynamic response to the induction, was correlated with fluid responsiveness.

A metagenômica independente de cultura é um meio atraente e promissor para explorar pequenas moléculas bioativas únicas de esponjas marinhas que abrigam micro-organismos simbiontes não cultiváveis. Foi realizada uma triagem funcional da biblioteca metagenômica da esponja marinha japonesa Discodermia calyx. O fracionamento bio-guiado do extrato cultivado em placas do clone bactericida pDC113 produziu onze ciclodipeptídeos: Ciclo(L-Thr-L-Leu) (1), Ciclo(L-Val-D-Pro) (2), Ciclo(L-Ile-D-Pro) (3), Ciclo(L-Leu-L-Pro) (4), Ciclo(L-Val-L-Leu) (5), Ciclo(L-Leu-L-Ile) (6), Ciclo(L-Leu-L-Leu) (7), Ciclo(L-Phe-L-Tyr) (8), Ciclo(L-Trp-L-Pro) (9), Ciclo(L-Val-L-Trp) (10) e Ciclo(L-Ile-L-Trp) (11). Eles são os primeiros ciclodipeptídeos isolados a partir de uma biblioteca metagenômica. A análise sequencial indicou que os ciclodipeptídeos isolados não foram sintetizados por peptídeo sintetases não ribossomais e não havia indícios significativos de sintetases ciclodipeptídicas.

Culture-independent metagenomics is an attractive and promising approach to explore unique bioactive small molecules from marine sponges harboring uncultured symbiotic microbes. Therefore, we conducted functional screening of the metagenomic library constructed from the Japanese marine sponge Discodermia calyx. Bioassay-guided fractionation of plate culture extract of antibacterial clone pDC113 afforded eleven cyclodipeptides: Cyclo(L-Thr-L-Leu) (1), Cyclo(L-Val-D-Pro) (2), Cyclo(L-Ile-D-Pro) (3), Cyclo(L-Leu-L-Pro) (4), Cyclo(L-Val-L-Leu) (5), Cyclo(L-Leu-L-Ile) (6), Cyclo(L-Leu-L-Leu) (7), Cyclo(L-Phe-L-Tyr) (8), Cyclo(L-Trp-L-Pro) (9), Cyclo(L-Val-L-Trp) (10) and Cyclo(L-Ile-L-Trp) (11). To the best of our knowledge, these are first cyclodepeptides isolated from metagenomic library. Sequence analysis suggested that isolated cyclodipeptides were not synthesized by nonribosomal peptide synthetases and there was no significant indication of cyclodipeptide synthetases.