Asunto(s)
Androstenos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Acetato de Abiraterona , Androstenos/administración & dosificación , Animales , Ensayos Clínicos como Asunto , Humanos , Masculino , Comprimidos , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Sulfonamidas/uso terapéutico , Antivirales/administración & dosificación , Antivirales/química , Cápsulas/administración & dosificación , Cápsulas/uso terapéutico , Ensayos Clínicos como Asunto , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/química , Humanos , Simeprevir , Sulfonamidas/administración & dosificación , Sulfonamidas/química , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismoAsunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacocinética , Artritis Psoriásica/tratamiento farmacológico , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Semivida , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Ratones , Receptores Fc/fisiologíaAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Ensayos Clínicos como Asunto , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Nitrilos/uso terapéutico , Pirimidinas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Reacciones Cruzadas , Farmacorresistencia Viral , Quimioterapia Combinada , Infecciones por VIH/virología , Humanos , Nitrilos/efectos adversos , Nitrilos/química , Nitrilos/farmacología , Pirimidinas/efectos adversos , Pirimidinas/química , Pirimidinas/farmacología , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacología , RilpivirinaAsunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Galantamina/farmacología , Galantamina/uso terapéutico , Acetilcolina/agonistas , Animales , Inhibidores de la Colinesterasa/administración & dosificación , Galantamina/administración & dosificación , Humanos , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Fármacos Neuroprotectores , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores NicotínicosAsunto(s)
Isoxazoles/farmacología , Pirimidinas/farmacología , Esquizofrenia/tratamiento farmacológico , Animales , Conducta Animal/efectos de los fármacos , Catalepsia/inducido químicamente , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Humanos , Isoxazoles/administración & dosificación , Isoxazoles/efectos adversos , Isoxazoles/metabolismo , Isoxazoles/uso terapéutico , Palmitato de Paliperidona , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Pirimidinas/metabolismo , Pirimidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor de Serotonina 5-HT2A/metabolismo , Receptores de Dopamina D2/metabolismo , Prevención SecundariaRESUMEN
Parasites are ubiquitous in natural systems and ecosystem-level effects should be proportional to the amount of biomass or energy flow altered by the parasites. Here we quantified the extent to which a manipulative parasite altered the flow of energy through a forest-stream ecosystem. In a Japanese headwater stream, camel crickets and grasshoppers (Orthoptera) were 20 times more likely to enter a stream if infected by a nematomorph parasite (Gordionus spp.), corroborating evidence that nematomorphs manipulate their hosts to seek water where the parasites emerge as free-living adults. Endangered Japanese trout (Salvelinus leucomaenis japonicus) readily ate these infected orthopterans, which due to their abundance, accounted for 60% of the annual energy intake of the trout population. Trout grew fastest in the fall, when nematomorphs were driving energy-rich orthopterans into the stream. When infected orthopterans were available, trout did not eat benthic invertebrates in proportion to their abundance, leading to the potential for cascading, indirect effects through the forest-stream ecosystem. These results provide the first quantitative evidence that a manipulative parasite can dramatically alter the flow of energy through and across ecosystems.
Asunto(s)
Ecosistema , Enfermedades de los Peces/parasitología , Helmintos/fisiología , Ríos , Trucha/parasitología , Animales , Metabolismo Energético/fisiología , Interacciones Huésped-Parásitos , Factores de TiempoAsunto(s)
Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Transcriptasa Inversa del VIH/farmacología , Transcriptasa Inversa del VIH/uso terapéutico , Piridazinas/farmacología , Piridazinas/uso terapéutico , Replicación Viral/efectos de los fármacos , Fármacos Anti-VIH/química , Ensayos Clínicos Fase III como Asunto , Depresión Química , Farmacorresistencia Viral , Quimioterapia Combinada , Transcriptasa Inversa del VIH/química , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Nitrilos , Piridazinas/química , Pirimidinas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: : We examined the effects of methylphenidate hydrochloride (MPH) on the cardiovascular system using in vivo and in vitro study methods in accordance with the ICH-S7B guideline. METHODS: MPH was orally administered at doses of 3, 10 and 30 mg/kg to unrestrained conscious dogs implanted with a telemetry transmitter and attached with body surface electrodes, and electrocardiogram (ECG) leads. The QTcF interval was determined while heart rate (HR), and blood pressure (BP) were measured. Action potentials in isolated guinea-pig papillary muscle and the rapid component of the delayed rectifier potassium current (I(Kr)) in HEK-293 cells stably transfected with hERG were also investigated at concentrations of 0.1, 0.3 and 1 microg/mL (0.37, 1.1 and 3.7 micromol/L) of MPH. RESULTS: No ECG changes were observed except for a shortening of the QT interval due to a shortening of the RR interval at the maximum dose tested, 30 mg/kg. The only observed change was an elevation of BP in dogs at the dose of 30 mg/kg, which is approximately 10 times higher than the maximum therapeutic dose for use in children with attention deficit hyperactivity disorder (ADHD). Neither APD prolongation nor I(Kr) inhibition was observed by MPH in the in vitro studies up to the maximum concentration tested, 1 microg/mL (3.7 micromol/L), which is approximately 34 times higher than the clinically attainable unbound plasma MPH concentrations in children with ADHD. DISCUSSION: These results suggest that it is unlikely that MPH affects ventricular repolarization processes at the therapeutically recommended dose levels in patients with ADHD.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Metilfenidato/farmacología , Potenciales de Acción/efectos de los fármacos , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Línea Celular , Estimulantes del Sistema Nervioso Central/efectos adversos , Canales de Potasio de Tipo Rectificador Tardío/antagonistas & inhibidores , Perros , Relación Dosis-Respuesta a Droga , Electrocardiografía , Canales de Potasio Éter-A-Go-Go/genética , Canales de Potasio Éter-A-Go-Go/fisiología , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Técnicas In Vitro , Masculino , Metilfenidato/efectos adversos , Músculos Papilares/efectos de los fármacos , Músculos Papilares/fisiología , TelemetríaAsunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH , VIH-1 , Sulfonamidas , Ensayos Clínicos Fase III como Asunto , Darunavir , Farmacorresistencia Viral , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/crecimiento & desarrollo , Humanos , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacologíaRESUMEN
In resource-based promiscuous mating systems, synchronous spawning of females affects competition among males and variation in the reproductive success of males. We documented the mating behavior of Japanese charr (Salvelinus leucomaenis japonicus) through an annual breeding season to examine the relationship between female spawning synchrony and male mating behavior. Females spawned highly synchronously in the population studied, i.e., approximately half the spawning was finished within the first three days of the entire spawning season (11 days). The daily operational sex ratio (OSR) was nearly 1:1 through the spawning period. The number of males around a spawning female was very small (1.21+/-0.49 males per female) over the spawning ground and period, suggesting that a competitive male could effectively chase subordinate males away from a spawning female. A few males attempted to sneak near the oviposition site of females (16%; 9 of 57 breeding groups), while some males adopted sneaking tactics in the initial phase of females' spawning (24%). We did not observe any males to succeed in sneak fertilizations. We conclude that in this Japanese charr population, the synchronous spawning of females was related to the unbiased daily OSR, male aggregation around females, and consequently whether and how efficiently males engaged in sneak mating behavior.
Asunto(s)
Oviposición/fisiología , Conducta Sexual Animal/fisiología , Trucha/fisiología , Animales , Femenino , Masculino , Densidad de Población , Factores de TiempoAsunto(s)
Antineoplásicos/farmacología , Ácidos Borónicos/farmacología , Ácidos Borónicos/uso terapéutico , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , Pirazinas/farmacología , Pirazinas/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Bortezomib , HumanosAsunto(s)
Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/farmacología , Anestesia General , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/farmacología , Piperidinas/administración & dosificación , Piperidinas/farmacología , Anestésicos por Inhalación , Animales , Ensayos Clínicos Fase III como Asunto , Combinación de Medicamentos , Humanos , Infusiones Intravenosas , Éteres Metílicos , Propofol , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Remifentanilo , SevofluranoAsunto(s)
Antifúngicos , Candidiasis Bucal/tratamiento farmacológico , Itraconazol , Administración Oral , Animales , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/farmacocinética , Antifúngicos/farmacología , Candidiasis Bucal/microbiología , Modelos Animales de Enfermedad , Farmacorresistencia Fúngica , Hongos/efectos de los fármacos , Humanos , Absorción Intestinal , Itraconazol/administración & dosificación , Itraconazol/efectos adversos , Itraconazol/farmacocinética , Itraconazol/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , SolucionesRESUMEN
To analyse the effects of current income on the nature of size-number trade-off and optimal offspring size, we developed a model in which offspring grow by absorbing current income and reserves. The offspring continue to grow while the current income is available or the reserves exist, and they cease to grow when the reserves are depleted and the current income ceases. We showed that the size-number trade-off is nonlinear in the region where the number of offspring is smaller than the critical number and linear in the region where the number of offspring is greater than the critical number. In the former region, the reserves are not depleted by the time the current income ceases and the offspring cease to grow when the reserves are depleted, whereas in the latter region, the reserves are depleted before the current income ceases and the offspring production is completed when the current income ceases. The optimal offspring size is the same as that shown in Sakai and Harada (Evolution 55 (2001) 467) if this optimal size is realized in the region of nonlinear trade-off, whereas the optimal offspring size is the same as that shown in Smith and Fretwell (Am. Natur. 108 (1974) 499) if this optimal size is realized in the region of linear trade-off.
Asunto(s)
Evolución Biológica , Crecimiento , Tamaño de la Camada , Modelos Económicos , Reproducción , Animales , Modelos BiológicosRESUMEN
We analysed the nature of size-number trade-off of offspring when multiple cohorts of such offspring are produced sequentially using a fixed amount of reserves. In the model, we incorporated sink-limitation in the resource absorption rate of offspring from the mother tissue and the loss of resources by maintenance respiration. We found that the later the initiation of a cohort, the greater the cost of producing a cohort with the same size and number of offspring. This is due to the loss of resources by maintenance respiration during the period from the beginning of reproduction to the initiation of the cohort. Also, the extra cost increases with an increase in the specific maintenance respiration rate. Thus, resources lost to respiration over time reduces the fitness value of producing late cohorts. Hence, it is advantageous to produce all offspring simultaneously unless there are fitness advantages of producing offspring sequential which overcome this cost or constraints preventing simultaneous production. Sequentially offspring production evolves if there is a constraint on the number of offspring of each cohort. With this constraint, the optimal offspring size decreases with the production sequence of cohorts.
Asunto(s)
Tamaño de la Camada , Modelos Biológicos , Reproducción/fisiología , Animales , Crecimiento/fisiología , Consumo de Oxígeno/fisiologíaRESUMEN
We analyzed sexual allocation in cosexual plants while taking the trade-off between growth and reproduction into consideration and showed that this trade-off does not select for female-biased sexual allocation. There are two problems in sexual allocation: optimizing the amount of resources allocated to reproduction in a growing season and equalizing the resources allocated to the male and the female functions. If these two are possible at the same time, equal resource allocation to the male and the female functions is the evolutionarily stable strategy (ESS; given that the fitness gains through the male and the female functions are proportional to the amount of the resources allocated to these functions). Biased sexual allocation only occurs when constraints make it impossible to simultaneously optimize allocation to reproduction and allocation to male and female functions. However, even if female-biased sexual allocation occurs due to the addition of other constraints, the trade-off between growth and reproduction itself is not an important factor that selects for female-biased sexual allocation.