RESUMEN Introducción: El fentanilo de administración transmucosa tiene características específicas que lo convierten en el fármaco adecuado para el tratamiento del dolor irruptivo oncológico (DIO). ...Aunque en España existe un amplio consenso sobre la idoneidad de la administración de fentanilo transmucoso para el DIO, es relevante conocer cómo los oncólogos adecuan su prescripción al paciente y cuáles son los factores determinantes de la elección de las diferentes formas farmacéuticas. Objetivos: El objetivo principal de este proyecto fue identificar y priorizar los atributos que los oncólogos médicos españoles tienen en cuenta cuando valoran las opciones de tratamiento con fentanilo transmucoso en pacientes con DIO. Métodos: Un comité científico realizó una tipificación de 14 atributos relevantes en la prescripción de fentanilo transmucoso para el DIO. Posteriormente se generó un dossier de evidencia científica comparando estos 14 atributos entre los distintos fentanilos transmucosos disponibles, que se compartió con el panel de expertos (115 oncólogos médicos). Tras una exhaustiva revisión del documento, los participantes realizaron una votación online de priorización de los atributos. Resultados: De catorce atributos analizados, siete consiguieron un consenso de ≥ 50 % de los participantes: el inicio de la acción analgésica (84 %), la adecuación del efecto del fentanilo al perfil del episodio de DIO (72 %), la facilidad de uso por los pacientes y cuidadores (69 %), la duración del efecto (58 %), la presencia de mucositis (57 %),la facilidad de titulación de la dosis óptima (57 %) y las presentaciones y dosis disponibles (59 %). Conclusiones: Los atributos más valorados fueron los relativos a la rapidez de acción del tratamiento analgésico y su adaptación al perfil del DIO, algo esperable dadas las características clínicas del episodio de DIO. Como atributos menos valorados aparecen el riesgo de abuso o conductas aberrantes y la presencia de rinitis para su administración, lo que indica que la existencia de estos factores no tiene tanta influencia en la elección del tratamiento para el abordaje del DIO. Estos resultados permitirán a los oncólogos médicos conocer qué atributos deben ser tenidos en cuenta a la hora de personalizar los tratamientos del paciente con DIO con el objetivo de mejorar la adecuación de la analgesia de rescate.
Lens cells demonstrate a terminal differentiation process with loss of their organelles including nuclei. Chromatin disappearance is characterised by the same changes as most apoptotic cells, i.e. ...condensation of chromatin and cleavage into high molecular weight fragments and oligonucleosomes. The endo-deoxyribonucleases (bicationic (Ca2+, Mg2+), mono-cationic (Ca2+ or Mg2+) and acidic non-cationic dependent nucleases) are present in lens fibre cells. Our results suggest that the acidic non-cationic nuclease (DNase II) plays a major role in chromatin cleavage. This nuclease, known to be lysosomal, is found in lens fibre nuclei and only an antibody directed against DNase II inhibits the acidic DNA cleavage of lens fibre nuclei. In addition, there must be another DNase implicated in the process which is not DNase I but appears to be a Ca2+, Mg2+ dependent molecule. Regulation of these DNase activities may be accomplished by the effect of post-translational modifications, acidic pH, mitochondrial release molecules, growth factors or oncogenes. Finally, fibre cells lose organelles without cytoplasmic elimination. The survival of these differentiated cells might be due to the action of survival factors such as FGF 1.
In order to compare the anti-ischemic activity of gallopamil and nifedipine, a cross-over, double-blind, randomised trial was carried out in 30 male out-patients with a history of stable exertional ...angina, proven coronary disease and a positive stress test (ST-segment depression > or = 1 mm). After a first 1-week wash-out period on placebo, the patients were randomised to gallopamil, 150 mg/day (50, 50 and 50) or nifedipine, 30 mg/day (10, 10 and 10) for 28 days. After a second 1-week wash-out period active treatments were crossed for another 28 days. At the end of each drug or placebo period, a physical examination, laboratory tests and a stress test were performed. Oral short-acting nitrates were permitted throughout the trial periods. Twenty-one patients finished all periods of the study. Both drugs reduced the maximum ST-segment depression during the exercise test: from 2.45 +/- 0.97 mm (placebo) to 1.95 +/- 0.82 mm (gallopamil, P < 0.05) and from 2.50 +/- 0.93 mm (placebo) to 1.75 +/- 0.84 mm (nifedipine, P < 0.05). Gallopamil but not nifedipine increased stress tolerance significantly: from 486 +/- 156 s (placebo) to 598 +/- 138 s (gallopamil, P < 0.05) and from 509 +/- 113 s (placebo) to 567 +/- 191 s (nifedipine, NS). No significant differences were found between drugs. Both calcium antagonists, gallopamil and nifedipine, showed similar efficacy in treating myocardial ischemia.
Epithelial cells from the lens equator differentiate into elongated fiber cells. In the final steps of differentiation, the chromatin appears quite condensed and chromatin breakdown into nucleosomes ...occurs. DNA breaks due to an endodeoxyribonuclease activity corresponding to at least two polypeptides of 30 and 40 kDa have been identified. To identify the nature and the developmental appearance of initial breaks, nick translation reaction was followed both biochemically and in situ in fiber and epithelial cells from chick embryonic lenses. There is no accumulation of single-strand breaks (SSB) with 3'OH ends in lens fiber cells during embryonic development. Such damage can be increased in these cells by treatment with DNAase I indicating the absence of an inhibitor of the nick translation reaction in fiber cells. However, there are indications of the presence of DNA breaks with blocked termini when the phosphatase activity of nuclease P1 is used. The presence of breaks is also indicated by the large amounts of (ADP-ribose)n found in lens fibers particularly at 11 days of embryonic development (E11) as ADP-ribosyl transferase binds to and is activated by DNA strand breaks. Incubation of lens cells in vitro, which causes nucleosomal fragmentation only in fiber cells, produces SSB with 3'OH ends in both epithelia and fibers. Incubation for short periods, observed in experiments in situ, induces SSB first in the central fiber nuclei, which are late in differentiation. This may indicate that these SSB play a physiological role. Long incubations produce larger numbers of SSB in epithelia than fibers. The SSB in the fibers may have been converted into double-strand breaks (D SB), seen as nucleosomal fragments, and therefore no longer act as substrates for nick translation. The nuclease activity responsible for SSB production is independent of divalent cations and could be implicated in lens terminal differentiation.
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