RESUMEN
Rapid eye movement sleep (REM) is increased after controllable stress (modeled by escapable footshock, ES) and decreased after uncontrollable stress (modeled by inescapable footshock, IS). Decreases in REM after IS are exacerbated by corticotropin releasing factor (CRF) and attenuated by a CRF antagonist. In this study, we trained mice with ES following injections of CRF, astressin (AST), or saline (SAL) to determine whether CRF would alter REM after ES. Male BALB/cJ mice (n=7) were implanted for recording sleep, activity and body temperature via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery, sleep following exposure to a novel chamber was recorded as a handling control (HC). The mice received one day of training with ES without injection followed by weekly training sessions in which they received counterbalanced intracerebroventricular (ICV) microinjections of either SAL or CRF (days 7 & 14) or SAL or AST (days 21 & 28) prior to ES. On each experimental day, sleep was recorded for 20 h. Compared to HC, the mice showed significantly increased REM when receiving either SAL or AST prior to ES whereas CRF prior to ES significantly reduced REM. Stress-induced hyperthermia had longer duration after ES compared to HC, and was not significantly altered by CRF or AST compared to SAL. The current results demonstrate that activity in the central CRF system is an important regulator of stress-induced alterations in REM.
Asunto(s)
Temperatura Corporal/efectos de los fármacos , Hormona Liberadora de Corticotropina/farmacología , Electrochoque/efectos adversos , Estrés Psicológico/etiología , Estrés Psicológico/fisiopatología , Análisis de Varianza , Animales , Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Hormona Liberadora de Corticotropina/uso terapéutico , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Pie/inervación , Inyecciones Intraventriculares/métodos , Ratones , Fragmentos de Péptidos/farmacología , Sueño REM/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Factores de TiempoRESUMEN
Corticotropin releasing hormone (CRH) plays a major role in central nervous system responses to stressors and has been implicated in stress-induced alterations in sleep. In the absence of stressors, CRH contributes to the regulation of spontaneous waking. We examined the effects of CRH and astressin (AST), a non-specific CRH antagonist, on wakefulness and sleep in two mouse strains with differential responsiveness to stress to determine whether CRH might also differentially affect undisturbed sleep and activity. Less reactive C57BL/6J (n=7) and high reactive BALB/cJ (n=7) male mice were implanted with a transmitter for determining sleep via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery and habituation to handling, ICV microinjections of CRH (0.04, 0.2, and 0.4 microg), AST (0.1, 0.4, and 1.0 microg) or vehicle alone (pyrogen-free saline, 0.2 microl) were administered during the fourth hour after lights on and sleep was recorded for the subsequent 8 h. Comparisons of wakefulness and sleep were conducted across conditions and across strains. In C57BL/6J mice, REM was significantly decreased after microinjections of CRH (0.2 microg) and CRH (0.4 microg), and NREM and total sleep were decreased after microinjections of CRH (0.4 microg). CRH (0.04 microg) and AST did not significantly change wakefulness or sleep. In BALB/cJ mice, CRH (0.4 microg) increased wakefulness and decreased NREM, REM and total sleep. AST decreased active wakefulness and significantly increased REM at the low and high dosages. These findings demonstrate that CRH produces changes in arousal when given to otherwise undisturbed mice. Strain differences in the effects of CRH and AST may be linked to the relative responsiveness of C57BL/6J and BALB/cJ mice to stressors and to underlying differences in the CRH system.
Asunto(s)
Hormona Liberadora de Corticotropina/fisiología , Actividad Motora/fisiología , Fases del Sueño/fisiología , Vigilia/fisiología , Animales , Nivel de Alerta/fisiología , Hormona Liberadora de Corticotropina/administración & dosificación , Inyecciones Intraventriculares , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Microinyecciones , Fragmentos de Péptidos/fisiología , Especificidad de la EspecieRESUMEN
A brief exposure of hippocampal slices to L-quisqualic acid sensitizes CA1 pyramidal neurons 30-250-fold to depolarization by two classes of excitatory amino acid analogues: (1) those whose depolarizing effects are rapidly terminated following washout, e.g. L-2-amino-4-phosphonobutanoic acid (L-AP4) and L-2-amino-6-phosphonohexanoic acid (L-AP6) and (2) those whose depolarizing effects persist following washout, e.g. L-aspartate-beta-hydroxamate (L-AbetaH). This process has been termed quisqualate sensitization. In this study we directly examine the role of amino acid transport systems in the induction of quisqualate sensitization. We report that L-quisqualate is a low-affinity substrate (K(M)=0.54 mM) for a high capacity (V(max)=0.9 nmol (mg protein)(-1) min(-1)) Na(+)-dependent transport system(s) and a high-affinity substrate (K(M)=0.033 mM) for a low-capacity (V(max)=0.051 nmol (mg protein)(-1) min(-1)) transporter with properties similar to the cystine/glutamate exchange carrier, System x(c-). We present evidence that suggests that System x(c-) participates in quisqualate sensitization. First, simultaneous application of L-quisqualate and inhibitors of System x(c-), but not inhibitors of Na(+)-dependent glutamate transporters, prevents the subsequent sensitization of hippocampal neurons to phosphonates or L-AbetaH. Second, L-quisqualic acid only sensitizes hippocampal neurons to other substrates of System x(c-), including cystine. Third, immunocytochemical analysis of L-quisqualate uptake demonstrates that only inhibitors of System x(c-) inhibit the highly concentrative uptake of L-quisqualate into a widely dispersed group of GABAergic hippocampal interneurons. We conclude that quisqualate sensitization is a direct consequence of the unique interaction of various excitatory amino acids, namely L-quisqualate, cystine, and phosphonates, with the exchange carrier, System x(c-). Therefore, the results of this study have important implications for the mechanism by which L-quisqualate, and other substrates of this transporter which are also excitatory amino acid agonists (such as glutamate and beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, beta-L-ODAP) may trigger neurotoxicity.
Asunto(s)
Proteínas Portadoras/metabolismo , Membrana Celular/metabolismo , Cistina/metabolismo , Hipocampo/metabolismo , Células Piramidales/metabolismo , Ácido Quiscuálico/farmacocinética , Animales , Transporte Biológico Activo/efectos de los fármacos , Transporte Biológico Activo/fisiología , Proteínas Portadoras/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Cistina/farmacocinética , Interacciones Farmacológicas/fisiología , Inhibidores Enzimáticos/farmacología , Ácido Glutámico/metabolismo , Hipocampo/citología , Hipocampo/efectos de los fármacos , Inmunohistoquímica , Interneuronas/citología , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Neurotoxinas/metabolismo , Técnicas de Cultivo de Órganos , Farmacocinética , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Radioisótopos de Azufre/farmacocinética , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The Objective Structured Clinical Examination (OSCE) for student assessment is well established, with an extensive body of research documenting that this is a valid means to assess clinical skills that are fundamental to the practice of medicine. The OSCE consists of a circuit of stations which tests a range of skills and learning to assess undergraduate medical students. A well-constructed OSCE provides important information about candidate performance and the quality of training. It is used at the University of South Dakota School of Medicine (USDSM) in assessment of third year medical students during their Obstetrics Clerkship, and as a teaching tool in the Pediatric Clerkship. On August 10, 1996, the USDSM administered an OSCE for the first time to third year medical students. The purpose of this article is to present state of the art information about setting up OSCE based on our recent experience and to provide practical examples of OSCE questions which can be addressed in the clinical setting. The narrative, references and examples give guidelines for the preparation of OSCE testing. The OSCE provided a standardized way of assessing clinical competence. Both students and faculty were very satisfied with the examination, and felt that the material tested was relevant and appropriate. The OSCE process does serve to identify areas of weakness in the curriculum and/or teaching methods, and thus can serve as a mechanism to improve educational effectiveness.
Asunto(s)
Prácticas Clínicas/métodos , Competencia Clínica/normas , Medicina Clínica/educación , Evaluación Educacional/métodos , Estudiantes de Medicina , Medicina Clínica/métodos , HumanosRESUMEN
A questionnaire assessing physicians' understanding of the prognosis of preterm newborns was sent to every pediatrician, obstetrician, family practitioner, and general practitioner in South Dakota. Fifty-three percent of the total sample completed and returned the questionnaire that covered the mortality, general care, and physical, developmental, and psychosocial morbidity of the preterm newborn. The average physician answered 75% of all items with responses consistent with our interpretation of the medical literature. The physicians did better on items concerning mortality and physical morbidity than on those items related to psychosocial or developmental morbidity. Stepwise multiple regression analysis showed that a physician's years of experience was the most significant predictive variable and was negatively related to his or her overall score.
Asunto(s)
Recien Nacido Prematuro , Médicos , Humanos , Mortalidad Infantil , Recién Nacido , Morbilidad , Pronóstico , Encuestas y CuestionariosAsunto(s)
Enfermedades del Prematuro , Recien Nacido Prematuro , Médicos , Recolección de Datos , Medicina Familiar y Comunitaria , Femenino , Humanos , Recién Nacido , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/mortalidad , Obstetricia , Pediatría , Embarazo , South DakotaAsunto(s)
Parto Obstétrico/métodos , Recién Nacido , Resucitación , Corazón/fisiología , Humanos , RespiraciónRESUMEN
Intra-amniotic prostaglandin F2alpha, in doses of 2.5 to 20 mg, combined with 80 gm of urea, was an effective, safe, simple, and economical midtrimester abortifacient in 115 patients. The mean abortal time, 15.8 hours, was significantly less than that in prior series in which intra-amniotic hypertonic saline or urea was administered together with constant, intravenous oxytocin infusion. The use of intracervical laminaria tents did not shorten the abortal time. Only eight patients had not aborted within 30 hours; only two had not aborted within 36 hours; and only six received a second intra-amniotic injection. Operative removal of the placenta, when necessary, was accomplished under intravenous sedation in a treatment room. The incidence of infection, nausea, vomiting, and other complications was low.
PIP: A study involving 115 women was conducted to determine the effectiveness of doses of PGR2alpha (prostaglandin F2alpha) and urea for 2nd trimester abortions. 2.5-20 mg of PGF2alpha was combined with 80 gm of urea to induced abortion, with 10 mg being the optimal dose. Only 2 patients had not aborted after 36 hours and only 6 patients required a 2nd injection at 24 hours; laminaria tents did not shorten abortal times. For 33 multiparous patients the mean abortal time was 14.3 hours and for 82 nulliparous women, the mean abortal time was 16.4 hours. 30% of the women had the placenta removed operatively using intravenous sedation. Vomiting occurred in 19 women, nausea in 4 women, 8 became febrile, 2 received blood transfusions for hemorrhage, and 2 had a 4-cm cervical laceration