RESUMEN
PURPOSE: To better understand how quantitative sensory testing could help the clinician in the management of oxaliplatin-induced peripheral neuropathy in terms of earlier and more reliable detection, we conducted a two-year prospective study. METHODS: Thermal sensory assessment, tactile sensory assessment, neuropathic pain assessment and adverse events gradation (NCI-CTC) were performed during treatment and 6 months after treatment completion. RESULTS: 35 patients were enrolled and followed-up during one year. Cold and Warm Detection Thresholds were higher 6 months after treatment completion than at enrollment. Mechanical detection thresholds didn't change significantly. Neurotoxicity was mostly grade-1, only 18% grade-2 and no grade-3. Grade-2 patients received lower oxaliplatin cumulative dose than grade-1, which reveals effective dose adaptation and grade-2 patients were more likely to develop painful neuropathy. CONCLUSION: Thermal thresholds impairment emerges too late to help the clinician in the prophylaxis of neuropathy. Management of OXA-treatment based on NCI-CTC, as currently recommended, remains the best way to detect neuropathy and ensure treatment adaptation.
Asunto(s)
Antineoplásicos/efectos adversos , Síndromes de Neurotoxicidad/terapia , Oxaliplatino/efectos adversos , Sensación Térmica/fisiología , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/inducido químicamente , Síndromes de Neurotoxicidad/etiología , Dimensión del Dolor , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios Prospectivos , Percepción del Tacto/fisiología , Resultado del TratamientoRESUMEN
Despite years of investigation, pathogenesis of necrotizing enterocolitis (NEC) remains elusive. Bacterial metabolites were implicated by several authors but their roles remain controversial. The aim of our study was to investigate the role of SCFAs and polyamines through a kinetic study of histological and macroscopical digestive lesions in monobiotic quails. Germ-free quails, inoculated with a Clostridium butyricum strain involved in a NEC case, were fed or not with a diet including lactose (7%). Quails were sacrificed at various times between D7 and D24 after bacterial inoculation. NEC-like lesions, i.e. thickening, pneumatosis, and hemorrhages, occurred only in lactose-fed quails and increased with time. The main histological characteristics were infiltrates of mononuclear cells, then heterophilic cells, then gas cyst and necrosis. The first event observed, before histological and macroscopical lesions, is a high production of butyric acid, which precedes an increase of iNOS gene expression. No difference in polyamines contents depending on the diet was observed. These results show the major role of butyric acid produced by commensal bacteria in the onset of the digestive lesions.
Asunto(s)
Ciego , Enterocolitis Necrotizante/fisiopatología , Ácidos Grasos/metabolismo , Vida Libre de Gérmenes , Lactosa/administración & dosificación , Poliaminas/metabolismo , Codorniz , Animales , Ciego/metabolismo , Ciego/microbiología , Ciego/patología , Clostridium butyricum/metabolismo , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/microbiología , Humanos , Cinética , Lactosa/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
A rapid and simple method for the determination of main components and related substances of both neomycin sulfate and framycetin sulfate by HPLC and evaporative light scattering detection (ELSD) is described. The method was also used to determine the neomycin B and the sample sulfate content. Detection and quantitation of aminoglycoside antibiotics are problematic because of the lack of UV absorbing chromophore. The use of a universal detector avoids the need for sample derivatization or use of specific detector based on pulsed amperometry described to be difficult in routine assays. Separation was performed with a Polaris C18 150 mm x 4.6 mm i.d., 3 microm reversed-phase column with a solution of 170mM trifluoroacetic acid (TFA) mobile phase at a flow rate of 0.2 mL/min. The chromatographic parameters were optimized with the help of experimental design software. Mass spectrometry (MS) was employed to confirm the ELSD profile. The final method was validated using methodology described by the International Conference of Harmonization in the field of Active Pharmaceutical Ingredients. Commercial samples of different sources were analyzed and results were in good agreement with specifications of the European Pharmacopoeia.
Asunto(s)
Antibacterianos/análisis , Cromatografía Líquida de Alta Presión/métodos , Framicetina/análisis , Neomicina/análisis , Dispersión de Radiación , Luz , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
To gain a better understanding of the effect exerted by the 3-hydroxypicolinoyl residue on the antibiotic activity of Pristinamycin IA, the C-N bond of picolinamide was cleaved electrochemically. A mechanistic study demonstrated that the presence of the peptidic macrolactone M markedly modified the expected cathodic behavior of pyridylcarboxamides. In order to assess the influence of steric crowding exerted by M on this original behavior, we look for models using two different approachs. First, tertiary pyridylcarboxamides were used to increase steric hindrance at the amide nitrogen position; second, M was opened by ammonolysis to decrease steric crowding at the amide nitrogen position. The electrochemical behavior of the selected compounds is presented in the first and the second parts of this study. Determination of pyridine nitrogen basicity in an N-substituted-3-methoxypicolinamide series is treated in the third part as a useful probe to evaluate the intensity of steric crowding at the amide nitrogen position. Finally, in the last part of this work, we propose the use of the picolinoyl residue (C6H4N-CO-ou Pic) as a protecting group for amines in peptide synthesis.