RESUMO
The effects of cocaine on memory are controversial. Furthermore, the psychostimulant action of cocaine can be a critical issue in the interpretation of its effects on learning/memory models. The effects of a single administration of cocaine on memory were investigated during the presence of its motor stimulating effect or just after its termination. The plus-maze discriminative avoidance task (PM-DAT) was used because it provides simultaneous information about memory, anxiety and motor activity. In Experiment I, mice received saline, 7.5, 10, 15 or 30 mg/kg cocaine 5 min before the training session. In Experiment II, mice were trained 30 min after the injection of saline, 7.5, 10, 15 or 30 mg/kg cocaine. In Experiment III, mice received 30 mg/kg cocaine 30 min pre-training and pre-test. In Experiment IV, mice received 30 mg/kg cocaine immediately post-training. Tests were always conducted 24 h following the training session. Given 5 min before training, cocaine promoted a motor stimulant effect at the highest dose during the training session but did not impair memory. When cocaine was injected 30 min pre-training, the drug did not modify motor activity, but produced marked amnestic effects at all doses tested. This amnesia induced by cocaine given 30 min pre-training was not related to a state-dependent learning because it was not abolished by pre-test administration of the drug. Post-training cocaine administration did not induce memory deficits either. Our results suggest that the post-stimulant phase is the critical moment for cocaine-induced memory deficit in a discriminative task in mice.
Assuntos
Amnésia/induzido quimicamente , Amnésia/fisiopatologia , Cocaína/efeitos adversos , Cocaína/farmacologia , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/farmacologia , Análise de Variância , Animais , Ansiedade/induzido quimicamente , Aprendizagem da Esquiva/efeitos dos fármacos , Discriminação Psicológica/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Fatores de TempoRESUMO
The effect of home cage conspecifics' behavior on locomotor sensitization to amphetamine (AMP) or ethanol (ETOH) were investigated. Female mice were repeatedly treated with saline or AMP (2.0 mg/kg for 13 days--Experiment 1) or saline or ETOH (1.8 g/kg for 21 days--Experiment 2) in home cages where all the animals had the same treatment (homogeneous home cages--HOM-HC) or in home cages where half of the animals were drug-treated and half of them were saline-treated (heterogeneous home cages--HET-HC). Behavioral sensitization was evaluated by the quantification of open-field locomotor activity after AMP or ETOH challenge injection, respectively. In both experiments, behavioral sensitization was potentiated in HOM-HC maintained animals. These results suggest that the behavioral sensitization phenomenon can be modified by home cage conspecifics' behavior.
Assuntos
Anfetamina/farmacologia , Comportamento Animal/efeitos dos fármacos , Etanol/farmacologia , Análise de Variância , Animais , Feminino , CamundongosRESUMO
La insulina, miembro de la familia de factores de crecimiento que incluyen al factor de crecimiento tipo insulina I (IGF-I) y II (IGF-II), presenta efectos mitogénicos sobre células epiteliales mamarias normales y malignas (Goodwin y col., 2002). Se postula que altos niveles de insulina permiten identificar mujeres con una mala evolución de su cáncer de mama, en quienes deberán aplicarse estrategias terapéuticas más efectivas. Se estudiaron 32 pacientes con cáncer de mama, de las cuales 18 presentaron carcinoma ductal invasor, incluidos 3 multifocales (56 por ciento), 6 carcinoma lobulillar infiltrante (19 por ciento), 3 carcinoma papilar (10 por ciento) y el resto otros tipos (15 por ciento). Dos pacientes (7 por ciento) presentan diabetes mellitus no-insulino dependiente. Los niveles de insulina plasmática en ayunas determinados por RIA (Insulin-CT kit) resultaron en: 18 pacientes (56 por ciento) con niveles normales (5,5 a 19,9 µUI/ml), el resto (44 por ciento) con insulinemias superiores al normal. La insulinemia plasmática en ayunas en voluntarias sanas resultó ser de 13,9ñ4,3 µUI/ml (n=10)...
Assuntos
Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Carcinoma Lobular , Carcinoma Papilar , Insulina , Antagonistas da Insulina , Biomarcadores Tumorais , Neoplasias da Mama , Insulina , Metástase Linfática , Prognóstico , Receptores de Estrogênio , Receptores de Progesterona , Receptores de Somatomedina , Taxa de SobrevidaRESUMO
La insulina, miembro de la familia de factores de crecimiento que incluyen al factor de crecimiento tipo insulina I (IGF-I) y II (IGF-II), presenta efectos mitogénicos sobre células epiteliales mamarias normales y malignas (Goodwin y col., 2002). Se postula que altos niveles de insulina permiten identificar mujeres con una mala evolución de su cáncer de mama, en quienes deberán aplicarse estrategias terapéuticas más efectivas. Se estudiaron 32 pacientes con cáncer de mama, de las cuales 18 presentaron carcinoma ductal invasor, incluidos 3 multifocales (56 por ciento), 6 carcinoma lobulillar infiltrante (19 por ciento), 3 carcinoma papilar (10 por ciento) y el resto otros tipos (15 por ciento). Dos pacientes (7 por ciento) presentan diabetes mellitus no-insulino dependiente. Los niveles de insulina plasmática en ayunas determinados por RIA (Insulin-CT kit) resultaron en: 18 pacientes (56 por ciento) con niveles normales (5,5 a 19,9 AUI/ml), el resto (44 por ciento) con insulinemias superiores al normal. La insulinemia plasmática en ayunas en voluntarias sanas resultó ser de 13,9ñ4,3 AUI/ml (n=10)...(AU)
Assuntos
Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico , Biomarcadores Tumorais , Carcinoma Intraductal não Infiltrante , Carcinoma Lobular , Carcinoma Papilar , Insulina/sangue , Antagonistas da Insulina/uso terapêutico , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/patologia , Prognóstico , Insulina/diagnóstico , Receptores de Estrogênio , Metástase Linfática , Receptores de Progesterona , Receptores de Somatomedina , Taxa de SobrevidaRESUMO
There is an increasing interest by health care providers, not only in the effectiveness of cancer treatments, but also in patients' quality of life (QOL). The objective of the present study is to validate the Functional Assessment of Cancer Therapy-General (FACT-G) Version 2 as a measure of the QOL in a sample of 140 Uruguayan patients with cancer of varied sites, at different stages of the disease and under different forms of treatment. Reliability of the FACT-G was evaluated and showed high coefficients (Cronbach's alpha) in each of the subscales and in the total questionnaire score. It was also capable of discriminating among different groups of patients. We conclude that the FACT-G is a brief and easy to use questionnaire, that showed acceptable reliability and validity and good feasibility for use as a research instrument among Uruguayan cancer patients.
Assuntos
Pacientes Internados/psicologia , Neoplasias/psicologia , Pacientes Ambulatoriais/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Reprodutibilidade dos Testes , Estudos de Amostragem , Traduções , UruguaiRESUMO
The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.
Assuntos
Anticarcinógenos/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Neoplasias Mamárias Experimentais/etiologia , Tamoxifeno/uso terapêutico , Animais , Antibacterianos , Carcinógenos/toxicidade , Divisão Celular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Insulina/sangue , Neoplasias Mamárias Experimentais/sangue , Neoplasias Mamárias Experimentais/patologia , Metilnitrosoureia/toxicidade , Ratos , EstreptozocinaRESUMO
A displacement assay with tamoxifen, based on the relative binding affinity of tamoxifen and estradiol for the estrogen receptor (ER), was proposed in 1990 as prognostic indicator for breast-cancer patients. Validation of its predictive results in relation to the outcome of 73 patients with ER+ tumors is analyzed. ER, progesterone receptor (PgR) determinations and other conventional prognostic factors in relation to the displacement assay, were considered. Displacement assay results allowed ER+ tumors to be grouped as displaceable (D) or weakly displaceable (WD), with the implication that D tumors should respond better to tamoxifen (Tam) administration. Survival and disease-free interval curves showed highly significant differences between patients with ER+ D and ER+ WD tumors. For survival, including all tumor stages, 73.9% of patients were alive at 9 years after surgery in the group with D tumors and 37.0% in the group with WD tumors (p < 0.005); relative contribution of the different stages is analyzed. Addition of axillary-node number increased the prognostic significance of displacement categories for survival and disease-free interval. PgR determination as another ER functional expression failed to show significant differences for survival and disease-free interval between ER+ PgR+ and ER+ PgR- tumors. Thus, results from the displacement assay and from PgR determinations reflect 2 independent ER functional expressions. Displacement assay data appear as reliable prognostic indicators of breast-cancer outcome, and contribute to more appropriate treatment decisions in this pathology.
Assuntos
Antineoplásicos Hormonais/metabolismo , Neoplasias da Mama/metabolismo , Estradiol/metabolismo , Antagonistas de Estrogênios/metabolismo , Receptores de Estrogênio/metabolismo , Tamoxifeno/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Receptores de Progesterona/metabolismoRESUMO
The type of hormone dependence in mammary neoplasias is usually defined by the presence or absence of estrogen and progesterone receptors. At present, new advances in the knowledge related to the functionality of these receptors are changing our previous concepts. Estrogen receptors classified as negative by biochemical or immunocytochemical methods because of deletions or mutations in their ligand-binding domain, are still able to regulate the expression of genes related to cellular proliferation. Receptors defined as positive, may present other defective domains with disappearance or distortion of their transcriptional function. As a result, regulation of the cellular proliferative process is distorted and the tumoral growth seems autonomous, as if the receptors were absent. The modular organization of the receptor molecule allows a relative functional independence of the constitutive domains. Functional assays to evaluate receptor behavior under different experimental or clinical situations are necessary. A displacement assay with tamoxifen, for studying the relative binding affinity of tamoxifen and estradiol for the estrogen receptor contributes to a more appropriate use of this antiestrogen in mammary oncology. Conformational changes and mutations in one or several of these genomic molecules may after the transcriptional message with repercussion on cellular proliferation. In this way, antiprogestinic agents can show progestin agonistic effects when combined with cAMP analogues; on the other hand, opposite effects on cellular growth by cAMP analogues can be observed according to the type of hormone dependency (autonomous or dependent) of the tumors. Modulation of steroid receptor transcriptional activity is also achieved through non-transcriptional proteins associated to the receptor molecule. These proteins are then potential targets for the pharmacological regulation of the transcription message. Resistance to antihormone treatments in breast cancer is a dominant feature in the evolution of this malignancy. It cannot be attributed to the presence or absence of steroid receptors when only defined by their quantitative variations.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias Hormônio-Dependentes/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Tamoxifeno/uso terapêuticoRESUMO
The contractile response of the rabbit urinary bladder smooth muscle to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic contraction. The phasic contraction is mediated by a rapid rise in intracellular free calcium concentration which in turn is achieved by a combination of the entry of extracellular calcium into the cell and by the mobilization and release of calcium from intracellular storage sites. Partial bladder outlet obstruction in rabbits is associated with a marked depression of contractile function. The current experiments were designed to: (1) investigate the role of extracellular calcium in mediating the phasic and tonic components of the contractile response to field stimulation and (2) determine the effect of partial outlet obstruction on this relationship. The results can be summarized as follows: in the control bladder, increasing the extracellular calcium concentration from 0.6 to 5.4 mmol/l enhanced the phasic contractile response to a 2-Hz stimulation to a significantly greater degree than the response to a 16-Hz stimulation. Increasing the extracellular calcium concentration had no effect on the plateau phase of the contractile response. Partial outlet obstruction significantly reduced the phasic and tonic responses to all frequencies of stimulation. In general, there was a greater reduction in the tonic response to field stimulation (relative to the phasic response).
Assuntos
Cálcio/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiopatologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Bexiga Urinária/fisiopatologia , Animais , Estimulação Elétrica , Masculino , CoelhosRESUMO
En una serie de 23 pacientes seguidas durante 4 y 5 años, se pudo constatar una alta correlación entre aquellas con tumores RE+ desplazables y la evolución favorables de su enfermedad (11 de 12 casos - 91 por ciento), así como una correlación entre los tumores RE+ poco desplazables y la evolución desfavorable de la enfermedad (3 de 4 casos - 75 por ciento). Este último grupo se homologa con los tumores RE - cuya evolución fue desfavorable. En esta serie, los tumores RE+ de las pacientes con evolución favorable, presentaron valores de RPg mayores de los RE (10 de 12 casos - 83 por ciento). En las pacientes con tumores RE+ la evolución desfavorable, los valores de RPg no fueron mayores que RE (3 de 4 casos - 75 por ciento). Los estudios anatomo-patológicos indicaron que los tumores RE+ desplazables presentaron mayor proporción de células más diferenciadas que el grupo de tumores RE. Los otros indicadores histológicos examinados: necrosis, desmoplasia, invasión linfocitaria, no mostraron correlación con grado de dependencia hormonal ni con la prueba de desplazamiento por Tam