RESUMEN

Bladder cancer is the most prevalent tumor in the genitourinary tract and the current treatments are not efficient to prevent recurrence and progression of tumor cases. Studies have revealed evidence of the involvement of the purinergic system in bladder tumorigenesis, particularly ecto-5'-NT/CD73, the enzyme responsible for AMP hydrolysis. Quercetin (3,3',4',5,7-pentahydroxyflavone) is a plant-derived flavonoid that has been shown to exert a broad range of pharmacologic properties, including potential anticancer activity. Here, we investigated the quercetin effect on the E-NTPDases and ecto-5'-nucleotidase/CD73, which catalyzes the introversion of the extracellular purine nucleotides in T24 human bladder cancer cells. The results showed that this flavonoid was able to increase ADP hydrolysis and inhibit the ecto-5'-nucleotidase/CD73 activity, with no effect on protein expression. The treatment with APCP (α,ß-methyleneadenosine-5'-diphosphate), another ecto-5'-NT/CD73 inhibitor, led to a significant reduction in cell proliferation. In addition, we showed that AMP, which can be accumulating by enzyme inhibition, had an antiproliferative effect on T24 cells, which was enhanced when its hydrolysis was inhibited by APCP treatment. Otherwise, adenosine did not cause any significant effect on cell proliferation and the quercetin effects were not altered by the simultaneous presence of adenosine. Taken together, the results suggest that the antiproliferative effect of quercetin on tumor cells may occur, at least in part, via alterations in the extracellular catabolism of nucleotides, that could be by AMP accumulation, or could be due to blocked adenosine receptors by this flavonoid, supporting the potential use of quercetin in bladder cancer treatment.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Espacio Extracelular/metabolismo , Nucleótidos/metabolismo , Quercetina/farmacología , 5'-Nucleotidasa/antagonistas & inhibidores , 5'-Nucleotidasa/metabolismo , Adenosina/farmacología , Adenosina Difosfato/análogos & derivados , Adenosina Difosfato/metabolismo , Adenosina Difosfato/farmacología , Adenosina Monofosfato/metabolismo , Adenosina Monofosfato/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/metabolismo , Humanos , Hidrólisis/efectos de los fármacos , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología

RESUMEN

This study evaluated the effects of different anti-TNFalpha strategies on the nociceptive and inflammatory responses triggered by formalin in the rat orofacial region. Formalin injection (2.5%) into the right upper lip caused a nociceptive response that was biphasic, with the first phase observed between 0 and 3 min and the second phase between 12 and 30 min. Plasma extravasation induced by formalin was time-related and reached the peak at 360 min. The monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) significantly inhibited the second phase of formalin-induced nociceptive behavior, while the first phase remained unaltered. The systemic treatment with the chimeric anti-TNFalpha antibody infliximab also caused a significant inhibition of the second phase. Interestingly, the local administration of infliximab (50 pg/lip) produced a significant reduction of both phases of formalin-induced nociception. In addition, the systemic pretreatment with the preferential inhibitor of TNFalpha synthesis thalidomide (25 and 50 mg/kg, p.o) promoted a marked reduction of the first and second phases of formalin-evoked nociception. The local administration of the monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) or infliximab (50 pg/lip) markedly reduced the plasma extravasation induced by formalin. Otherwise, formalin-elicited plasma extravasation was not significantly affected by the systemic administration of either infliximab (1 mg/kg; s.c) or thalidomide (50 mg/kg, p.o). Present data suggest that blocking TNFalpha effects, through different pharmacological tools, could represent a good alternative to control orofacial inflammatory pain that is refractory to other drugs.

Asunto(s)

Dolor Facial/inducido químicamente , Dolor Facial/patología , Formaldehído/toxicidad , Inflamación/inducido químicamente , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Conducta Animal/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Dolor Facial/psicología , Formaldehído/administración & dosificación , Formaldehído/farmacocinética , Inmunosupresores/uso terapéutico , Inflamación/patología , Infliximab , Inyecciones , Labio , Masculino , Dimensión del Dolor/efectos de los fármacos , Ratas , Ratas Wistar , Talidomida/uso terapéutico , Factor de Necrosis Tumoral alfa/farmacología

RESUMEN

UNLABELLED: The elderly population is one of the most rapidly increasing populations in the world. Physiological alterations induced by the aging process make these individuals more susceptible to chronic diseases and, consequently, to increased drug utilization. OBJECTIVE: To describe the profile of drug utilization in the elderly living in Porto Alegre, RS, Brazil. METHODS: An observational and cross-sectional population-based study to investigate the characteristics of the population, sources of information and types of drugs used by the elderly was performed. Four hundred and eighty patients were recruited from data supplied by the City Hall of Porto Alegre. The elderly were interviewed individually during the period from January to May 2006 by trained interviewers. A validated pharmacotherapy questionnaire was used for data collection and data were tabulated and analyzed by the SPSS 11.5 computer program. RESULTS: Of the 480 patients interviewed, 13.8% did not use any medication. Cardiovascular system drugs represented the pharmacological class most used by the elderly (64.0%). When ill, 71.9% of these individuals visited the doctor, while 36.9% self-medicated. For the majority (50.2%), drugs were identified by their labels. Only 41.2% of the elderly understood medical prescriptions and 68.3% of the patients studied obtained the necessary information for the appropriate use of therapy from their doctors. CONCLUSIONS: The present study suggests that a pharmaceutical care program for the treatment, prevention, and use of medications may provide a higher efficiency to elderly drug therapy.