RESUMEN
A novel approach to biotransformation is described using a solid medium matrix and Reemay mesh that gives efficient biotransformation of compounds with minimal matrices in the ensuing gum solids. Using this approach with a newly isolated biotransforming organism, Streptomyces lydicus SX1298, a series of hydroxylations and an O-demethylation is described for selamectin the first endectocide for cats and dogs.
Asunto(s)
Antiparasitarios/farmacocinética , Ivermectina/análogos & derivados , Ivermectina/farmacocinética , Streptomyces/metabolismo , Antiparasitarios/química , Antiparasitarios/metabolismo , Biotransformación , Cromatografía Liquida , Fermentación , Ivermectina/química , Ivermectina/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de MasasRESUMEN
Elaiophylin (1) and two new methyl derivatives, 11-O-monomethylelaiophylin (2) and 11,11'-O-dimethylelaiophylin (3), were isolated from the mycelium cake of Streptomyces strains HKI-0113 and HKI-0114. The structures of 2 and 3 were determined by mass spectrometric and NMR investigations. Compounds 2 and 3 display antimicrobial and moderate cytotoxic activities.
Asunto(s)
Antibacterianos/farmacología , Streptomyces/química , Animales , Antibacterianos/aislamiento & purificación , Bacterias/efectos de los fármacos , Candida albicans/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Macrólidos , Espectroscopía de Resonancia Magnética , Ratones , Espectrofotometría InfrarrojaRESUMEN
New anthracycline antibiotics 3'-O-demethyl mutactimycin (3) and 4-O,3'-O-didemethyl mutactimycin (4) were isolated from two actinomycetes strains, Nocardia transvalensis and Streptomyces sp. GW 60/1571. The chemical structures were elucidated by mass spectrometry and NMR spectroscopy. Antibiotic 3 displayed moderate antimicrobial activity against Gram-positive bacteria and cytotoxicity against P388, L1210 and HeLa tumor cells (IC50; 9.6, >25 and 20 microg/ml, respectively).
Asunto(s)
Antraciclinas , Antibióticos Antineoplásicos/aislamiento & purificación , Antibióticos Antineoplásicos/farmacología , Animales , Antibióticos Antineoplásicos/química , Fermentación , Bacterias Grampositivas/efectos de los fármacos , Células HeLa/efectos de los fármacos , Humanos , Leucemia L1210/tratamiento farmacológico , Leucemia P388/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Nocardia , Estereoisomerismo , Streptomyces , Relación Estructura-ActividadRESUMEN
The purpose of this single-dose, randomized, placebo-controlled, and double-blind study was to evaluate the analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen after third molar surgery. Patients were instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or 400 mg of ibuprofen when the postoperative pain was moderate to severe. Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain relief, and any possible adverse events were recorded on self-administered questionnaires hourly for 6 hours after intake of study medication. If rescue medication was taken, the time of intake was registered. A total of 304 patients entered the study, and 258 complied with the protocol. A positive analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen was observed when evaluated by pain intensity difference, sum of pain intensity difference, pain relief, total pain relief, and survival distribution of patients not taking rescue medication. Although significant pain relief was seen after a dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the longest duration of analgesic effect. Mild transient adverse events were reported by 6.8% of the patients. However, there was no significant difference in frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen dose groups.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Ibuprofeno/administración & dosificación , Tercer Molar/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Analgesia , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Dimensión del Dolor/efectos de los fármacosRESUMEN
A case of a nine year-old girl with a life-threatening episode of profuse bleeding after extraction of a loose deciduous molar is reported. An angiography confirmed the presence of a haemangioma in the right side of the mandible. The lesion was superselectively embolized. Two days later exploration of the haemangioma and resection of the bone was performed, and the bleeding stopped. Special concern must be exercised in cases with hypermobility of the teeth, and when episodes of spontaneous haemorrhage are encountered.
Asunto(s)
Hemangioma/diagnóstico , Neoplasias Mandibulares/diagnóstico , Hemorragia Bucal/diagnóstico , Femenino , Hemangioma/complicaciones , Humanos , Neoplasias Mandibulares/complicaciones , Hemorragia Bucal/etiología , Extracción Dental/efectos adversosRESUMEN
Nocardicyclins A (1) and B (2), new anthracycline antibiotics have been isolated from the mycelial cake of Nocardia pseudobrasiliensis IFM 0624 (JCM 9894). The molecular formulae of 1 and 2 have been determined as C30H35NO11 and C32H37NO12, respectively, and the structures were characterized by 1- and 8-methoxyl groups, a 10-carbonyl group and a novel carbon-methylated aminosugar constituent. Nocardicyclin A (1) exerts cytotoxic activity against L1210 and P388 leukemia. Nocardicyclins A (1) and B (2) are active against Gram-positive bacteria including Mycobacterium spp. and Nocardia spp., but inactive against Gram-negative bacteria.
Asunto(s)
Antraciclinas , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Nocardia/metabolismo , Antibióticos Antineoplásicos/metabolismo , Fermentación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Nocardia/químicaRESUMEN
Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Péptidos , Animales , Antibacterianos/química , Antifúngicos/química , Cromatografía Líquida de Alta Presión , Femenino , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Hongos Mitospóricos , Estructura Molecular , PeptaibolesAsunto(s)
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/aislamiento & purificación , Animales , Antibióticos Antineoplásicos/farmacología , Benzo(a)Antracenos/química , Benzo(a)Antracenos/aislamiento & purificación , Benzo(a)Antracenos/farmacología , Fermentación , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Streptomyces , Células Tumorales CultivadasRESUMEN
The Ekman-Westborg-Julin Syndrome is reveiwed and a new case reported.
Asunto(s)
Anomalías Dentarias/patología , Adolescente , Oído Externo/anomalías , Cara/anomalías , Humanos , Masculino , Diente Molar/anomalías , Odontometría , Prognatismo/patología , Síndrome , Corona del Diente/anomalías , Diente Primario/anomalíasRESUMEN
Specific microbial reactions were used for the preparation of metabolites of 3-ketodesogestrel (13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one, the active from of the progestagen desogestrel. Clostridium paraputrificum transformed 3-ketodesogestrel (KDG) to the 5 beta-dihydro and tetrahydro metabolites 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yn-3-one and 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol, respectively. The epimeric compound 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol was obtained by chemical reduction of the 3-oxo compound. Mycobacterium smegmatis converted KDG to metabolites of the 5 alpha H-series: 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yn-3-one, 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol and 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol. The ring A-aromatized analog of KDG 13-ethyl-11-methylene-18,19-dinor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17 beta-diol was obtained by microbial 1-dehydrogenation with Rhodococcus rhodochrous. Additionally, chemical syntheses of the microbially obtained KDG metabolites listed above were carried out. These included Birch reduction, reduction of KDG with sodium borohydride in aqueous pyridine and in methanol, reduction of KDG with potassium selectride in tetrahydrofuran, and dehydrogenation of KDG with cupric-II bromide in acetonitrile. The problems encountered in chemical syntheses favor the microbial procedures. The compounds were characterized by mass spectra (MS), IR, and circular dichroism (CD). Complete assignments of 1H and 13C chemical shifts were made using homo- and heteronuclear 2-DN-NMR spectroscopy. Chromatographic [gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC)] data of all the prepared KDG metabolites are presented.
Asunto(s)
Desogestrel/metabolismo , Congéneres de la Progesterona/metabolismo , Clostridium/metabolismo , Mycobacterium/metabolismo , Rhodococcus/metabolismoRESUMEN
Lipohexin was isolated as a novel lipohexapeptide (I) (C39H68N6O9) from three fungal strains, Moeszia lindtneri HKI-0054, Paecilomyces sp. HKI-0055 and Paecilomyces sp. HKI-0096. The structure was elucidated by detailed mass spectrometric and NMR experiments. The proline-containing peptide displays moderate antibacterial activity against Bacillus subtilis ATCC 6633 and inhibits competitively the prolyl endopeptidase from human placenta.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Lipoproteínas/aislamiento & purificación , Lipoproteínas/farmacología , Péptidos , Serina Endopeptidasas/metabolismo , Inhibidores de Serina Proteinasa/aislamiento & purificación , Inhibidores de Serina Proteinasa/farmacología , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Humanos , Lipoproteínas/química , Pruebas de Sensibilidad Microbiana , Hongos Mitospóricos/metabolismo , Estructura Molecular , Paecilomyces/metabolismo , Prolil Oligopeptidasas , Inhibidores de Serina Proteinasa/químicaRESUMEN
Four new members of peptaibol antibiotics, designated as chrysospermins A, B, C, and D, were isolated from the mycelium of Apiocrea chrysosperma Ap101 by solvent extraction, silica gel chromatography and preparative recycling HPLC. Their structures as new nonadecapeptides were settled by detailed spectroscopic analysis and chemical degradation experiments. The chrysospermins display antibacterial and antifungal activity, and induce pigment formation by the fungus Phoma destructiva.
Asunto(s)
Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Secuencia de Aminoácidos , Aminoácidos/análisis , Antibacterianos/farmacología , Antifúngicos/farmacología , Péptidos Catiónicos Antimicrobianos , Ascomicetos , Fermentación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Peptaiboles , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
Aurantimycins A (1), B (2) and C (3) were isolated from the mycelium of Streptomyces aurantiacus JA 4570 as new representatives of the azinothricin group of hexadepsipeptide antibiotics. Their structures were settled by X-ray diffraction analysis of crystalline aurantimycin A (1), high field homo- and heteronuclear 2D NMR experiments, high-resolution mass spectrometry and amino acid analysis. Aurantimycins are characterized by a new side chain containing fourteen carbon atoms. They display strong activity against Gram-positive bacteria and cytotoxic effects against L-929 mouse fibroblast cells.
Asunto(s)
Antibacterianos/biosíntesis , Péptidos , Streptomyces/metabolismo , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Línea Celular , Citotoxinas/biosíntesis , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Espectrometría de Masa Bombardeada por Átomos Veloces , Difracción de Rayos XRESUMEN
Helioferins A and B were detected as novel aminolipopeptides in cultures of Mycogone rosea DSM 8822 in the course of a screening for mediators of helianthate anion transfer from aqueous to toluene phases. Their structures as novel antibiotics and cytotoxic agents were elucidated by mass spectrometry and NMR spectroscopic methods. Antimicrobial activity was estimated against Candida albicans and Gram-positive bacteria including Mycobacterium spp.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Hongos Mitospóricos/química , Péptidos , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Espectrometría de Masa Bombardeada por Átomos VelocesAsunto(s)
Inhibidores de Fosfodiesterasa/aislamiento & purificación , Streptomyces/química , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Bovinos , Cromatografía Líquida de Alta Presión , Fermentación , Espectroscopía de Resonancia Magnética , Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/farmacología , EstereoisomerismoRESUMEN
The effect of a single preoperative dose of metronidazole in the prevention of alveolitis sicca dolorosa (ASD) after surgical removal of one impacted, non-infected mandibular third molar was investigated. A patient sample of 270 were given either 1000 mg of metronidazole or placebo at least 30 min before surgery. The preoperative recordings included gender, age, tooth to be removed, experience of surgeon, time of test medication, and duration of surgery. No difference was found between the metronidazole and placebo groups in the occurrence of ASD. The duration of surgery and the experience of the operating surgeons had no effect on the occurrence of ASD. The present study failed to demonstrate any preventive effect of a single dose of metronidazole on the development of ASD.