RESUMEN
Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins for heterotrimeric G proteins. One of the best-studied RGS proteins, RGS4, accelerates the rate of GTP hydrolysis by all G(i) and G(q) alpha subunits yet has been shown to exhibit receptor selectivity. Although RGS4 is expressed primarily in brain, its effect on modulating the activity of serotonergic receptors has not yet been reported. In the present study, transfected BE(2)-C human neuroblastoma cells expressing human 5-HT(1B) receptors were used to demonstrate that RGS4 can inhibit the coupling of 5-HT(1B) receptors to cellular signals. Serotonin and sumatriptan were found to stimulate activation of extracellular signal-regulated kinase. This activation was attenuated, but not completely inhibited, by RGS4. Similar inhibition by RGS4 of the protein kinase Akt was also observed. As RGS4 is expressed at high levels in brain, these results suggest that it may play a role in regulating serotonergic pathways.
Asunto(s)
Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas/metabolismo , Proteínas RGS/metabolismo , Receptores de Serotonina/fisiología , Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Activación Enzimática , Humanos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Neuroblastoma , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt , Proteínas RGS/genética , Receptor de Serotonina 5-HT1B , Receptores de Serotonina/genética , Proteínas Recombinantes/metabolismo , Serotonina/metabolismo , Células Tumorales CultivadasAsunto(s)
Colitis Ulcerosa/virología , Enfermedad de Crohn/virología , Virus del Sarampión , Sarampión/complicaciones , Complicaciones Infecciosas del Embarazo/virología , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Femenino , Humanos , Sarampión/prevención & control , Vacuna Antisarampión/administración & dosificación , Vacuna Antisarampión/efectos adversos , Embarazo , Factores de Riesgo , VacunaciónAsunto(s)
Anomalías Inducidas por Medicamentos/etiología , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Enfermedades del Recién Nacido/inducido químicamente , Animales , Diciclomina , Doxilamina/efectos adversos , Combinación de Medicamentos , Femenino , Antagonistas de los Receptores Histamínicos H1/química , Humanos , Recién Nacido , Leche Humana/química , Estudios Multicéntricos como Asunto , Embarazo , Piridoxina/efectos adversosAsunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Indometacina/toxicidad , Sulindac/toxicidad , Teratógenos/toxicidad , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Femenino , Humanos , Indometacina/farmacología , Indometacina/uso terapéutico , Embarazo , Sulindac/farmacología , Sulindac/uso terapéuticoAsunto(s)
Bifenilos Policlorados/toxicidad , Reproducción/efectos de los fármacos , Animales , Embrión de Mamíferos/efectos de los fármacos , Desarrollo Embrionario y Fetal/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Humanos , Leche/análisis , Bifenilos Policlorados/efectos adversos , Bifenilos Policlorados/análisis , EmbarazoRESUMEN
The use of non-prescription antacids to control hyperphosphatemia has been implicated as a primary cause of aluminum intoxications in patients with reduced renal function. Additional reports suggest that oral aluminum intake may have adverse effects on mineral metabolism of patients with normal renal function. The non-prescription drugs that contain substantial quantities of aluminum salts include some antacids, buffered aspirins, antidiarrheals, and vaginal douches. Sucralfate, an anti-ulcer drug available by prescription, is the aluminum salt of sucrose sulfate. If taken as directed, the daily aluminum intake from the antacids can be as much as 5,000 mg. When aluminum buffered aspirins are used as part of the drug therapy for rheumatoid arthritis, aluminum intake can be elevated by 700 mg/day. Although aluminum intoxications have been reported among patients with reduced renal function, existing reports are not sufficient to estimate whether the chronic elevation of aluminum intake from drugs is causing adverse health effects among other patient populations.
Asunto(s)
Aluminio/administración & dosificación , Antiulcerosos/administración & dosificación , Medicamentos sin Prescripción , Aluminio/efectos adversos , Antiácidos/administración & dosificación , Aspirina/administración & dosificación , Tampones (Química) , Humanos , SucralfatoAsunto(s)
Aluminio/efectos adversos , Aluminio/sangre , Aluminio/metabolismo , Animales , Antiácidos/efectos adversos , Antidiarreicos/efectos adversos , Proteínas Sanguíneas/metabolismo , Enfermedades Óseas/inducido químicamente , Tampones (Química) , Toxoide Diftérico/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina , Combinación de Medicamentos/administración & dosificación , Humanos , Absorción Intestinal , Minerales/metabolismo , Enfermedades del Sistema Nervioso/inducido químicamente , Análisis de Activación de Neutrones , Glándulas Paratiroides/efectos de los fármacos , Vacuna contra la Tos Ferina/administración & dosificación , Sucralfato , Líquido Sinovial/metabolismo , Toxoide Tetánico/administración & dosificación , Distribución Tisular , Uremia/complicaciones , Vitamina D/metabolismoRESUMEN
The aluminium content of coffee brewed and stored in aluminium percolators was measured using atomic absorption spectrometry. Brewing in a new aluminium pot added 0.88 (immediately after brewing ) to 1.18 mg aluminium (after a further 12-hr storage in the pot and reheating ) to each cup of coffee. Percolators which had been used repeatedly were less susceptible to mobilization of aluminium by coffee, and brewing in these increased the aluminium content of each cup of coffee by 0.40 mg immediately after brewing and by 0.58 mg after storage for 12 hr in the pot and reheating . The aluminium content of the ground coffee beans used in this work was relatively high (51.8 ppm). To demonstrate that the bulk of the aluminium measured in the percolated coffee samples were dissolved aluminium and was not part of the aluminium associated with the ground coffee, the dialysable aluminium was measured in some samples of coffee percolated in a new aluminium pot. These data indicate that 61% of the aluminium in the percolated coffee was dialysable immediately after brewing . Samples that were stored in a new aluminium percolator and reheated to 96 degrees C contained 75% dialysable aluminium. Although the levels of aluminium in percolated coffee have been measured, the bioavailability of the aluminium ingested in this way has yet to be determined.
Asunto(s)
Aluminio/análisis , Café/análisis , Utensilios de Comida y Culinaria , Dieta , HumanosRESUMEN
The use of modern analytical methods has demonstrated that aluminium salts can be absorbed from the gut and concentrated in various human tissues, including bone, the parathyroids and brain. The neurotoxicity of aluminium has been extensively characterized in rabbits and cats, and high concentrations of aluminium have been detected in the brain tissue of patients with Alzheimer's disease. Various reports have suggested that high aluminium intakes may be harmful to some patients with bone disease or renal impairment. Fatal aluminium-induced neuropathies have been reported in patients on renal dialysis. Since there are no demonstrable consequences of aluminium deprivation, the prophylactic reduction of aluminium intake by many patients would appear prudent. In this report, the major sources of aluminium in foods and non-prescription drugs are summarized and alternative products are described. The most common foods that contain substantial amounts of aluminium-containing additives include some processed cheeses, baking powders, cake mixes, frozen doughs, pancake mixes, self-raising flours and pickled vegetables. The aluminium-containing non-prescription drugs include some antacids, buffered aspirins, antidiarrhoeal products, douches and haemorrhoidal medications. The advisability of recommending a low aluminium diet for geriatric patients is discussed in detail.
Asunto(s)
Aluminio/administración & dosificación , Aluminio/análisis , Aluminio/toxicidad , Animales , Utensilios de Comida y Culinaria , Aditivos Alimentarios/análisis , Análisis de los Alimentos , Humanos , Absorción Intestinal/efectos de los fármacos , Minerales/metabolismo , Sistema Nervioso/efectos de los fármacos , Glándulas Paratiroides/metabolismoRESUMEN
The aluminium content of three chewing gums was measured before and after chewing. Analysis by atomic absorption spectrometry demonstrated that a single stick of chewing gum may contain as much as 4 mg aluminium. Analysis of samples after chewing revealed that between 2 and 21% of the aluminium in some chewing gums is mobilized during chewing. These data suggest that a stick of chewing gum can yield aluminium levels that correspond to 0.05-2.22% of the typical daily intake of aluminium from all dietary sources. Therefore, although the aluminium content of some chewing gums is relatively large, only a small proportion of the aluminium is mobilized by chewing. These gums are unlikely to contribute significantly to the daily intake of dietary aluminium.
Asunto(s)
Aluminio/aislamiento & purificación , Goma de Mascar/análisis , Humanos , Masticación , Espectrofotometría AtómicaRESUMEN
The derivation of the median volume (MV) and the geometric standard deviation (SDg) for a suspension of tumour cells quantifies the size and distribution of tumour cell aggregates in the suspension. Data collected in a group of 14 experiments shwoed a significant correlation of 0.80 (P less than 0.001) between the number of lung tumours formed by a suspension of B16 melanoma cells injected i.v. into C57BL/6J mice and the product of the MV and SDg of each cell suspension. These data define a size parameter of tumour cell suspensions that correlates with the intravascular survival properties of tumour cells.
Asunto(s)
Recuento de Células , Supervivencia Celular , Células Neoplásicas Circulantes , Animales , Agregación Celular , Neoplasias Pulmonares/patología , Masculino , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Neoplasias ExperimentalesRESUMEN
Heparin and warfarin inhibit the intravascular survival of B16 melanoma cells in syngeneic C57B1/6J mice in a dose-related manner. The anticoagulant properties of these drugs appear to mediate their inhibitory effects on the survival of intravascular tumor cells. Despite the administration of large doses of heparin, a constant fraction of tumor cells survive to form lung tumors. These data indicate that coagulation dependent and coagulation independent populations of B16 cells normally survive following the intravenous injection of tumor cells.