RESUMEN
Protoporphyrin IX, induced by the exogenous addition of delta-aminolevulinic acid, reaches different levels in different tumor cells. Because many of the steps in heme biosynthesis, of which protoporphyrin IX is penultimate, are located in the mitochondria, we surmised that the mitochondrial content of cells may relate to the amount of protoporphyrin IX synthesized in response to excess delta-aminolevulinic acid. We observed that accumulation of MitoTracker, a fluorescent mitochondrial probe, delta-aminolevulinic acid-induced protoporphyrin IX levels, and porphobilinogen deaminase activity all presented with the same cell-line-dependent rank order among the four different neoplastic cells. This rank order, however, differed for cytochrome c oxidase activity, the final enzyme in mitochondrial electron transport, and for accumulation of radioactive label from [(14)C]delta-aminolevulinic acid. The data demonstrate that enzymes involved in heme biosynthesis, in general, display a rank order associated with mitochondrial content. These data imply that such parameters may have value as prognosticators of cells to produce delta-aminolevulinic acid-induced protoporphyrin IX, a photosensitizer for photodynamic therapy of cancer.
Asunto(s)
Ácido Aminolevulínico/farmacología , Mitocondrias/metabolismo , Protoporfirinas/metabolismo , Animales , Complejo IV de Transporte de Electrones/metabolismo , Ferroquelatasa/metabolismo , Colorantes Fluorescentes , Humanos , Hidroximetilbilano Sintasa/metabolismo , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Oxidorreductasas/metabolismo , Fotoquimioterapia , Fármacos Fotosensibilizantes/metabolismo , Porfobilinógeno Sintasa/metabolismo , Células Tumorales CultivadasRESUMEN
Bacterial adhesion is a crucial factor in the pathogenicity of numerous bacterial species. This property plays such a great role in infections of foreign material that removal of the material is the only effective therapy. The electron microscopy studies performed by Christensen have demonstrated that infected foreign material harbors bacteria which are often coated with slime and therefore escape detection by conventional microbiological methods. in view of these properties, enzymatic or physical detachment of adherent bacteria was attempted. 231 specimens from a variety of materials (catheters, heart valves, drains, bone biopsies) which yielded negative results after 15 days culture in Schaedler medium were either exposed to trypsin or sonicated. Among catheter specimens, 44.7% yielded positive bacteriologic results; pathogens recovered included 8.3% micrococci, 5.1% nongroupable streptococci, 1.7% group D streptococci, 2.9% Enterobacteria, and 23.3% coagulase-negative staphylococci. Among the bone specimens, the improvement in yield was 64.7%; except in one case, the pathogens recovered were consistent with previously initiated treatments. This bacterial detachment method should be studied in a larger number of specimens to determine its diagnostic value as compared with conventional techniques.
Asunto(s)
Adhesión Bacteriana/efectos de los fármacos , Osteomielitis/diagnóstico , Sonicación , Infecciones Estafilocócicas/diagnóstico , Tripsina/farmacología , Bioprótesis , Catéteres de Permanencia/efectos adversos , Enfermedad Crónica , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/microbiología , Prótesis Valvulares Cardíacas/efectos adversos , Humanos , Técnicas In Vitro , Osteomielitis/etiología , Osteomielitis/microbiología , Estudios Retrospectivos , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/aislamiento & purificaciónRESUMEN
A better understanding of the pharmacokinetics of pefloxacin in human bone is warranted by the efficacy of this drug in the treatment of bone and joint infections. Surgical bone samples were taken at 30 mn, 1h, 6h, 12h and 24 h after the administration of a single 800 mg intravenous dose of pefloxacin over 1 hour for 26 patients who underwent surgery in an orthopedic surgery ward. Drug concentration was measured by a microbiological method (extraction of the antibiotic in buffer or with chloroform). Up until the 24th hour, in 25/26 cases, the bone levels were superior to 2 mg/l (the critical concentration of pefloxacin) in cortical as well as in spongy bone. Our study reveals a good diffusion of pefloxacin in bone, results which support the idea that this antibiotic may be prophylactically effective in orthopedic surgery.
Asunto(s)
Huesos/metabolismo , Pefloxacina/farmacocinética , Huesos/cirugía , Cloroformo , Difusión , Femenino , Humanos , Infusiones Intravenosas , Masculino , Pefloxacina/administración & dosificación , Pefloxacina/análisis , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
Selection of rifampicin-resistant Staphylococcus aureus has been described in vitro and in vivo when this compound is given as monotherapy or orally. That this occurrence may be prevented by combination antibiotic therapy is generally accepted. We report 25 cases of severe staphylococcal infection treated by a synergistic association of rifampicin with an aminoglycoside, vancomycin, or a macrolide. Therapy failed as a result of selection of the same rifampicin-resistant Staphylococcus aureus (serotype and lysotype) in seven cases. This finding may be explained by insufficient diffusion or inactivation of the other antibiotic in the infection site.
Asunto(s)
Rifampin/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Adolescente , Adulto , Anciano , Farmacorresistencia Microbiana , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genéticaRESUMEN
Four patients were studied following an anaphylactoid accident occurring during general anaesthesia. Histamine release was assessed on clinical signs, basophil degranulation and, in one case, an early serum histamine peak. Past medical history revealed previous allergies in all cases. An immunological study showed that IgE, CH50, C3 and C4 serum levels were within the normal range. Skin reactivity to histamine was normal in all but one case. In every case, one of the drugs used during the anaesthetic gave a positive skin test and was considered as the causative agent. There were discrepancies between the in vitro and in vivo tests of basophil degranulation, a second drug being positive in one case, and several drugs inducing abnormal degranulation reactions in the other cases. The drugs considered as involved in these accidents are noteworthy: suxamethonium (two cases), fluid gelatin (Plasmion) and droperidol. The results are discussed by the authors.