Characterization of l‑Digitoxosyl-phenanthroviridin from <i>Streptomyces venezuelae</i> ISP5230

The jadomycin-derived compound l-digitoxosyl-phenanthroviridin was isolated from fermentations of <i>Streptomyces venezuelae</i> ISP5230 grown in nutrient-deficient media with l-lysine as the sole nitrogen source. Structural elucidation was accomplished using a combination of high-resolution MS, LC-MS/MS, and 1D- and 2D-NMR. The compound was evaluated against the National Cancer Institute (NCI) 60 human tumor cell line screen in both the one-dose and five-dose screens, and cytotoxicity was compared to a small library of jadomycin analogues to probe the structure–activity relationship

Synthesis and Evaluation of l‑Rhamnose 1C-Phosphonates as Nucleotidylyltransferase Inhibitors

We report the synthesis of a series of phosphonates and ketosephosphonates possessing an l-rhamnose scaffold with varying degrees of fluorination. These compounds were evaluated as potential inhibitors of α-d-glucose 1-phosphate thymidylyltransferase (Cps2L), the first enzyme in Streptococcus pneumoniae l-rhamnose biosynthesis, and a novel antibiotic target. Enzyme–substrate and enzyme–inhibitor binding experiments were performed using water-ligand observed binding via gradient spectroscopy (WaterLOGSY) NMR for known sugar nucleotide substrates and selected phosphonate analogues. IC₅₀ values were measured and <i>K</i>_i values were calculated for inhibitors. New insights were gained into the binding promiscuity of enzymes within the prokaryotic l-rhamnose biosynthetic pathway (Cps2L, RmlB–D) and into the mechanism of inhibition for the most potent inhibitor in the series, l-rhamnose 1C-phosphonate

Peripheral intravenous infusion in newborns infants: reasons for infusion discontinuance and involveed factors

A terapia intravenosa periferica, parte da assistencia de enfermagem ao recem-nascido, fica sob cuidados e responsabilidade da enfermagem. A partir da prescricao medica, e a enfermeira que determinara o local, tipo e calibre do dispositivo, modo de fixacao e de instalacao desta terapia intravenosa, incluindo aspectos relacionados a diluicao e incompatibilidade medicamentosa. Com o objetivo de identificar os motivos que acarretam a interrupcao da infusao intravenosa, analisar o tempo de permanencia de cada dispositivo intravascular e solucoes utilizadas, realizou-se um estudo descritivo correlacional prospectivo em 650 insercoes intravenosas perifericas, tendo sido 331(50,9 por cento) realizadas com dispositivo agulha com asas e 319(4 9,1 por cento) com dispositivo cateter platico. Foram estudados 100 recem-nascidos pre-termo, subdivididos em tres grupos de acordo com a idade gestacional. Os dados deste estudo foram coletados no periodo de outubro de 1996 a outubro de 1997. Os resultados revelam que os principais motivos de interrupcao intravenosa foram, em ordem decrescente, a infiltracao , a flebite e a necrose. A agulha com asas e o catetor plastico nao apresentaram diferencas significante em relacao ao local de insercao(cabeca, membros superiores e membros inferiores) e tempo de permanencia. A presenca de flebite foi mais frequente (19,1 por cento) no dispositivo cateter plastico do que no dispositivo agulha com asas (8,5 por cento). Oteste de Fisher mostrou associacao significante entre o uso do gluconato de calcio 10 por cento, do cloreto de potassio 19,1 por cento e a presenca de necrose e entre o uso associado de cloreto de sodio 3 por cento, cloreto de potassio 19,1 por cento e glicose 50 por cento e a presenca de flebite. A escolha inadequada do dispositivo intravascular pode pesar na qualidade de assistencia de enfermagem, de forma a ocasionar sofrimento adicional e, sobretudo, desnecessario ao recem-nascido. Medidas para evitar a infiltracao, flebite e necrose continuam sendo imprescindiveis, pois estas ocorrencias implicam necessariamente, na retirada da insercao e consequente reinsercao, quando incontrolavelmente repetida resulta na inacessibilidade de veias perifericas e, por conseguinte, na inevitabilidade do acesso por via centralBV UNIFESP: Teses e dissertaçõe

CASA-F: Uma Ferramenta para Obtenção de Pontos de Controle por Casamento de Feições

Um problema freqüentemente encontrado em registro de imagens é a obtenção de pontos de controle. Uma quantidade razoável de pontos de controle é necessária para que um processo de registro de imagens seja realizado com sucesso. Em imagens que cobrem uma vasta região, nem sempre estes pontos de controle são encontrados com facilidade. Este artigo apresenta uma ferramenta, que está em fase em desenvolvimento, para a obtenção de pontos de controle a partir da extração e casamento de feições

Jadomycins Derived from the Assimilation and Incorporation of Norvaline and Norleucine

<i>Streptomyces venezuelae</i> ISP5230 is recognized for the production of chloramphenicol and the jadomycin family of natural products. The jadomycins are angucycline natural products containing a unique oxazolone ring incorporating an amino acid present in the minimal culture media. Substitution of different amino acids results in products of varying biological activity. Analysis of cultures of <i>S. venezuelae</i> ISP5230 incubated with l- and d-norvaline and l- and d-norleucine indicated that only the d-configured amino acids were incorporated into the natural products. Subsequently, jadomycin DNV and jadomycin DNL were isolated and characterized (titers 4 and 9 mg L^–1, respectively). The compounds were evaluated in the National Cancer Institute cell line cancer growth inhibition and cytotoxicity screens, for antimicrobial activity against selected Gram-positive and Gram-negative bacteria, and as DNA-cleavage agents <i>in vitro</i>

Eight-Membered Ring-Containing Jadomycins: Implications for Non-enzymatic Natural Products Biosynthesis

Jadomycin Oct (<b>1</b>) was isolated from Streptomyces venezuelae ISP5230 and characterized as a structurally unique eight-membered l-ornithine ring-containing jadomycin. The structure was elucidated through the semisynthetic derivatization of starting material via chemoselective acylation of the l-ornithine α-amino group using activated succinimidyl esters. Incorporation of 5-aminovaleric acid led to jadomycin AVA, a second eight-membered ring-containing jadomycin. These natural products illustrate the structural diversity permissible from a non-enzymatic step within a biosynthetic pathway and exemplifies the potential for discovery of novel scaffolds

150 µm³ axial, saggital and transverse MRI images.

<p>A mouse injected with SOR-C27-SPIO at each MRI time point showing <b><i>i</i></b> baseline tumor site, <b><i>ii</i></b> the accumulation of SPIO at 2 hours post-injection and <b><i>iii</i></b> SPIO persistence at tumor site at 26 hours post-injection (<b>A</b>). A mouse injected with SPIO control bead at each MRI time point showing <b><i>i</i></b> baseline tumor site, <b><i>ii</i></b> the initial accumulation of SPIO at 2 hours post-injection and <b><i>iii</i></b> SPIO clearance at tumor site at 26 hours post-injection (<b>B</b>).</p

<i>In vivo</i> optical imaging of mice bearing SKOV-3 xenograft tumors after i.p. administration of 100 µg of SOR-C27 tagged with Cy5.5.

<p>Dorsal whole-body images at indicated time points after injection of either SOR-C27-Cy5.5 (upper panels of <b>A</b>) or SOR-C27-Cy5.5 competitively blocked by 100 fold excess of SOR-C27 (lower panels of <b>A</b>). Arrows indicate the location of the solid subcutaneous tumor in the flank of the animal. Graph illustrating the changes in average fluorescence concentration in the tumor at indicated times after injection of SOR-C27-Cy5.5 or SOR-C27-Cy5.5 competitively blocked by SOR-C27 (<b>B</b>). <i>Ex vivo</i> optical images of mouse organs 24 hours post-injection of SOR-C27-Cy5.5 alone (left panel of <b>C</b>) or SOR-C27-Cy5.5 competitively blocked by SOR-C27 (right panel of <b>C</b>). Graph illustrating the average fluorescence concentration imaged <i>ex vivo</i> in various tissues 24 hours post-injection of SOR-C27-Cy5.5 or SOR-C27-Cy5.5 competitively blocked by SOR-C27 (<b>D</b>). *Indicates significant difference between SOR-C27-Cy5.5 and SOR-C27-Cy5.5 competitively blocked SOR-C27-Cy5.5 (<i>p</i><0.05). In <b>B</b> and <b>D</b>, data are expressed as mean ± SEM for <i>n</i> = 3 animals.</p

Long (τ₁) and short (τ₂) fluorescence lifetime components and their weighted average value τ_av (%) measured in <i>ex vivo</i> organs of mice bearing SKOV-3 xenograft tumors after injection with SOR-C27-Cy5.5 derived from a two-exponent model.

<p>Long (τ₁) and short (τ₂) fluorescence lifetime components and their weighted average value τ_av (%) measured in <i>ex vivo</i> organs of mice bearing SKOV-3 xenograft tumors after injection with SOR-C27-Cy5.5 derived from a two-exponent model.</p

Amino acid sequences of parent soricidin (accession number P0C2P6), SOR-C27 and SOR-C13.

<p>Amino acid sequences of parent soricidin (accession number P0C2P6), SOR-C27 and SOR-C13.</p