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1.
J Infus Nurs ; 39(1): 18-24, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26714115

RESUMEN

The aim of this randomized single-blind study is to compare taste and odor disturbances in patients receiving 0.9% sodium chloride flushes from 2 brands. Seventy-five patients from 6 to 18 years of age received intravenous 0.9% sodium chloride infusions, and 50 healthy volunteers who tasted the 2 brands of 0.9% sodium chloride from prefilled syringes were assessed for taste and/or odor disturbances. Taste or odor disturbances were equally present in patients flushed with MedXL and Becton-Dickinson 0.9% sodium chloride. Disturbances are more frequent when 0.9% sodium chloride is flushed through central venous access devices than through peripheral catheters. No difference between the brands was found when healthy volunteers tasted it orally.


Asunto(s)
Odorantes , Cloruro de Sodio/administración & dosificación , Jeringas , Gusto , Adolescente , Adulto , Cateterismo Venoso Central , Cateterismo Periférico , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego
2.
Oncogene ; 22(23): 3578-88, 2003 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-12789266

RESUMEN

Neoplastic transformation sensitizes many cells to apoptosis. This phenomenon may underlie the therapeutic benefit of many anticancer drugs, but its molecular basis is poorly understood. We have used a selective and potent farnesyltransferase inhibitor (FTI) to probe a mechanism of apoptosis that is peculiarly linked to neoplastic transformation. While nontoxic to untransformed mouse cells, FTI triggers a massive RhoB-dependent, p53-independent apoptosis in mouse cells that are neoplastically transformed. Here we offer evidence that the BAR adapter-encoding tumor suppressor gene Bin1 is required for this transformation-selective death program. Targeted deletion of Bin1 in primary mouse embyro fibroblasts (MEFs) transformed by E1A+Ras did not affect FTI-induced reversion, actin fiber formation, or growth inhibition, but it abolished FTI-induced apoptosis. The previously defined requirement for RhoB in these effects suggests that Bin1 adapter proteins act downstream or in parallel to RhoB in cell death signaling. The death defect in Bin1 null cells was significant insofar as it abolished FTI efficacy in tumor xenograft assays. p53 deletion did not phenocopy the effects of Bin1 deletion. However, MEFs transformed by SV40 large T antigen+Ras were also resistant to apoptosis by FTI, consistent with other evidence that large T inhibits Bin1-dependent cell death by a p53-independent mechanism. Taken together, the results define a function for Bin1 in apoptosis that is conditional on transformation stress. This study advances understanding of the functions of BAR adapter proteins, which are poorly understood, by revealing genetic interactions with an Rho small GTPase that functions in stress signaling. The frequent losses of Bin1 expression that occur in human breast and prostate cancers may promote tumor progression and limit susceptibility to FTI or other therapeutic agents that exploit the heightened sensitivity of neoplastic cells to apoptosis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Transferasas Alquil y Aril/antagonistas & inhibidores , Apoptosis/fisiología , Proteínas Portadoras/metabolismo , Transformación Celular Neoplásica/metabolismo , Inhibidores Enzimáticos/farmacología , Metionina/análogos & derivados , Proteínas del Tejido Nervioso , Proteínas Nucleares/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Actinas/metabolismo , Actinas/ultraestructura , Proteínas E1A de Adenovirus/genética , Proteínas E1A de Adenovirus/metabolismo , Transferasas Alquil y Aril/metabolismo , Animales , Antígenos Transformadores de Poliomavirus/genética , Antígenos Transformadores de Poliomavirus/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/genética , División Celular/efectos de los fármacos , División Celular/fisiología , Transformación Celular Neoplásica/genética , Células Cultivadas , Farnesiltransferasa , Fibroblastos/patología , Eliminación de Gen , Proteínas de la Membrana/metabolismo , Metionina/farmacología , Ratones , Ratones SCID , Proteínas Nucleares/efectos de los fármacos , Proteínas Nucleares/genética , Estrés Fisiológico , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/efectos de los fármacos , Proteínas Supresoras de Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas ras/genética , Proteínas ras/metabolismo , Proteína de Unión al GTP rhoB/genética , Proteína de Unión al GTP rhoB/metabolismo
3.
J Med Chem ; 45(24): 5233-48, 2002 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-12431051

RESUMEN

The identification of indeno[1,2-c]pyrazol-4-ones as inhibitors of cyclin-dependent kinases (CDKs) has led to the discovery of a series of novel and potent compounds. Herein, we report the effects of substitutions at C3 of the indeno[1,2-c]pyrazol-4-one core with alkyls, heterocycles, and substituted phenyls. Substitutions at the para position of the phenyl ring at C3 were generally well-tolerated; however, larger groups were generally inactive. For alkyls directly attached to C3, longer chain substituents were not tolerated; however, shorter alkyl groups and cyclic alkyls were acceptable. In general, the heterocycles at C3 gave the most potent analogues. One such heterocycle, 24j, was examined in detail and was determined to have a biological profile consistent with CDK inhibition. An X-ray crystal structure of one of the alkyl compounds, 13q, complexed with CDK2 was determined and showed the inhibitor residing in the adenosine 5'-triphosphate pocket of the enzyme.


Asunto(s)
Quinasas CDC2-CDC28 , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Proteínas Proto-Oncogénicas , Pirazoles/síntesis química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis , División Celular/efectos de los fármacos , Cristalografía por Rayos X , Quinasa 2 Dependiente de la Ciclina , Quinasa 4 Dependiente de la Ciclina , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Cinética , Modelos Moleculares , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Pirazoles/química , Pirazoles/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas
4.
Can J Hosp Pharm ; 67(5): 353-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25364017

RESUMEN

BACKGROUND: Previous studies have reported the occurrence of taste and odour disturbances among patients undergoing IV flush with prefilled syringes of 0.9% sodium chloride (normal saline [NS]). These disturbances have been attributed to the leaching of volatile substances into the NS from the plastic of the syringe. To date, there have been no studies comparing the occurrence of taste and odour disturbances with different NS preparations. OBJECTIVE: To compare the occurrence of taste and odour disturbances in pediatric patients undergoing IV flush with commercially available prefilled NS syringes and NS syringes prepared fresh daily. METHODS: Patients aged 6 to 18 years who underwent routine flushing of central or peripheral IV tubing were asked to participate in this follow-up randomized single-blind study. Flushing was performed with NS from BD PosiFlush 10-mL sterile prefilled syringes or NS transferred from a polyolefin bag (Baxter AVIVA) to a polypropylene syringe and stored for a maximum of 12 h before use. RESULTS: Fifty pediatric patients (mean age ± standard deviation 13.4 ± 3.8 years) who had undergone flushing of IV tubing with NS were interviewed. Taste or odour disturbances were reported by 18 (72%) of the 25 patients who underwent flushing with NS from a prefilled syringe, whereas only 1 (4%) of the 25 who underwent flushing with NS from a freshly prepared syringe experienced such disturbances (p < 0.001). CONCLUSIONS: There were significant differences in taste and odour disturbances experienced by patients who underwent IV flush with commercial prefilled NS syringes and freshly prepared NS syringes.


CONTEXTE: Des études antérieures ont signalé des cas d'altération du goût et de l'odorat chez des patients lors du rinçage de leur tubulure intraveineuse (i.v.) au moyen de seringues préremplies d'une solution de chlorure de sodium à 0,9 % (solution physiologique salée [SP]). Ces cas d'altération ont été attribués à des substances volatiles qui se seraient échappées du matériel composant la seringue plastique pour passer dans la SP. À ce jour, aucune étude comparant les cas d'altération du goût et de l'odorat en fonction de l'utilisation de différentes SP n'a été effectuée. OBJECTIF: Comparer les cas d'altération du goût et de l'odorat chez des enfants dont la tubulure i.v. a été rincée à l'aide d'une seringue commerciale préremplie de SP et chez ceux pour qui on a utilisé une seringue de SP préparée le jour même. MÉTHODES: On a demandé à des patients âgés de 6 à 18 ans chez qui on procédait à un rinçage habituel de leur tubulure i.v. périphérique ou centrale de participer à cette étude complémentaire avec répartition aléatoire et à simple insu. Le rinçage a été effectué à l'aide de la SP de seringues stériles préremplies BD PosiFlush de 10 mL ou à l'aide de SP prélevée d'un sac de polyoléfine (Baxter AVIVA) et introduite dans des seringues de polypropylène conservées pendant une période ne dépassant pas 24 heures avant l'utilisation. RÉSULTATS: Cinquante enfants (l'âge moyen ± l'écart-type était de 13,4 ± 3,8 ans) chez qui on a procédé à un rinçage de leur tubulure i.v. à l'aide d'une SP ont été interviewés. Des cas d'altération du goût ou de l'odorat ont été signalés par 18 (72 %) des 25 patients chez qui on a procédé à un rinçage à l'aide de la SP d'une seringue préremplie, alors qu'un seul (4 %) des 25 patients chez qui on a procédé à un rinçage à l'aide de la SP d'une seringue remplie dans les 24 heures précédentes a signalé un cas d'altération (p < 0.001). CONCLUSIONS: On a constaté d'importantes différences en ce qui a trait aux cas d'altération du goût et de l'odorat entre les patients chez qui on a procédé au rinçage des tubulures i.v. à l'aide de seringues commerciales préremplies de SP et ceux chez qui ont été utilisées des seringues remplies de SP dans les 24 heures précédentes. [Traduction par l'éditeur].

5.
Can J Hosp Pharm ; 65(5): 368-72, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23129865

RESUMEN

BACKGROUND: At the Children's Hospital of Eastern Ontario, more than 6000 inpatients per year undergo IV saline flushes by prefilled syringe to assess and maintain patency of IV tubing. In studies involving adults, it has been reported that volatile substances may leach from syringe materials into the saline, leading to taste and/or odour disturbances. OBJECTIVE: To determine the incidence of taste and/or odour disturbances in pediatric patients after flushing of IV tubing with 0.9% sodium chloride (normal saline [NS]) from prefilled syringes. METHODS: Inpatients aged 5-18 years who had undergone routine flushing of central or peripheral IV tubing with commercially available prefilled NS syringes were interviewed. Children aged 5-10 years used a visual hedonic scale to rate taste and odour sensations, and those aged 11-18 years used a numeric rating scale. RESULTS: During the study period (April to July 2011), a total of 104 pediatric inpatients (21 aged 5-10 years and 83 aged 11-18 years) underwent NS flushing of central (10 patients [10%]) or peripheral (94 patients [90%]) tubing. For 100 of these patients, BD Posiflush NaCl 0.9% 10-mL sterile prefilled syringes were used, and for 4 patients BD Saline XS NaCl 0.9% 10-mL sterile prefilled syringes were used. Taste and/or odour disturbances were reported by 76 (73%) of the patients. Twelve patients described more than one taste or odour sensation. Taste and odour disturbances were detected by children in both age groups. CONCLUSIONS: Flushing of IV tubing with prefilled NS syringes resulted in taste and/or odour disturbances in a pediatric population.

6.
Pain Manag Nurs ; 5(4): 144-52, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15616484

RESUMEN

Abstract Needle procedures are a necessary component of the treatment of hospitalized children. However, for many children they can be both painful and distressing. There was concern among the nurses at our pediatric hospital that we were not adequately controlling pain from needle procedures. We were interested in obtaining more information about the incidence and types of needle procedures and the current use of topical analgesics. A survey was designed to describe the frequency, type, time to complete, and perceived ease of needle procedures. The use of topical anesthetics and other comfort measures was also examined. The most common needle procedures performed were venipunctures for blood work, followed by intravenous cannulations, capillary sticks, port-a-cath access, and intramuscular injections. In total, 387 procedures were performed over a 23-day period. The majority of the procedures were perceived as easy, and the modal time to complete the procedures was 5 minutes. A topical anesthetic was used for 74 procedures (i.e., 19%), and the majority of these procedures were performed on the medical day unit with oncology patients. Results of the survey provided information about the day-to-day practice of needle procedures in order to identify both the supports and the barriers to providing these procedures atraumatically. Examining needle procedures within a framework of atraumatic care broadened our perspective and enabled us to integrate the use of topical anesthetics as just one of a number of strategies to minimize the pain and distress associated with needle procedures.


Asunto(s)
Lesiones por Pinchazo de Aguja/enfermería , Dolor/enfermería , Dolor/prevención & control , Enfermería Pediátrica/métodos , Adaptación Psicológica , Adolescente , Anestésicos Locales/uso terapéutico , Niño , Niño Hospitalizado , Preescolar , Recolección de Datos , Humanos , Lactante , Lesiones por Pinchazo de Aguja/psicología , Dolor/psicología
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