Uptake and release of [3H]dopamine by the median eminence: evidence for presynaptic dopaminergic receptors and for dopaminergic feedback inhibition

The accumulation and release of [3H]dopamine by the median eminence in vitro was studied after treatments with different pharmacological agents, to determine whether such a procedure would be useful for measuring neuronal activity in the tuberoinfundibular dopaminergic system. The accumulation of [3H]dopamine was temperature, time, and sodium dependent, and reduced by unlabelled dopamine and by a potent dopamine uptake blocker, nomifensine. The outflow of tritium was studied after blocking the oxidative deamination of dopamine by nialamide. The outflow of tritium was elicited consistently by biphasic square wave electrical pulses and by high molarity potassium ions. The response to electrical stimulation was dependent largely on calcium and partially on sodium. The response to high molarity potassium ions was reduced in the absence of calcium ions. The response to electrical stimulation was increased by nomifensine and by a dopaminergic antagonist, haloperidol, and was reduced by dopamine and by a dopaminergic agonist, piribedil. The inhibitory action of dopamine was antagonized by haloperidol. These results indicate the existence of uptake and release mechanisms in the tuberoinfundibular dopamine neurons, and suggest that dopamine may inhibit its own release via dopaminergic receptors. This in vitro method may be useful for measuring dopamine uptake and release by tuberoinfundibular dopaminergic neurons.     

Corticotropin-releasing hormone potentiates neural injury induced by oxygen-glucose deprivation: a possible involvement of microglia

While corticotropin-releasing hormone (CRH) has been implicated in a variety of brain disorders such as ischemic injury, the molecular mechanism by which CRH elicits its activities is largely unclear. In the present study, we have determined the effect of CRH on oxygen-glucose deprivation (OGD) induced apoptosis in fetal hippocampal neurons. CRH alone at concentrations of 10-200 nM had no effect on neuronal apoptosis. However, when neurons were co-cultured with microglia, CRH alone at concentrations greater than 100 nM induced neuronal apoptosis and CRH potentiated significant neuronal apoptosis following exposure to OGD. The effect of CRH on neuronal apoptosis was inhibited in the presence of the CRH antagonist astressin. Real-time RT-PCR revealed an increase in mRNA levels of Fas ligand (Fas-L), a membrane protein related to the TNF family, in cultured microglia following OGD exposure. In the presence of CRH, OGD-induced Fas-L expression was significantly increased. The effect of CRH on Fas-L expression was inhibited by specific inhibitors of the extracellular signal-regulated protein kinase (PD98059) and p38 mitogen-activated protein kinase (SB203580). These results suggest that CRH potentiates neuronal apoptosis induced by OGD in the presence of microglia and that this effect may be mediated through the induction of proinflammatory mediators in microglia.     

Stem cell therapy for the heart

Cellular cardiomyoplasty is an expanding field of research that involves numerous types of immature cells administered via several modes of delivery. The purpose of this review is to investigate the benefits of different types of cells used in stem cell research as well as the most efficient mode of delivery. The authors also present data showing that stem cells isolated from bone marrow are present at both 2 weeks and 3 months after engraftment in a myocardial infarction. These cells express muscle markers at both time points, which suggests that they have begun to differentiate into cardiomyocytes. Several questions must be answered, however, before stem cells can be used routinely in the clinic. Once these questions have been addressed, the use of stem cells in clinical practice can be realized.     

Relationship between information processing speed in temporal lobe epilepsy and white matter volume

Abnormalities in white matter have been linked to processing speed impairment in clinical populations (e.g., multiple sclerosis, closed head injury). Recent studies indicate the presence of significant reduction in cerebral white matter volume in some patients with chronic temporal lobe epilepsy (TLE). The objective of this study was to examine the relationship between white matter volume and processing speed and performance efficiency on the Sternberg Memory Scanning Test (SMST). The study groups included TLE subjects with white matter volume reduction (n=13), TLE subjects with normal white matter volume (n=14), and healthy controls (n=18). The groups did not differ in total cerebral gray matter volume. Compared with the controls, the reduced white matter volume TLE group exhibited a significantly steeper slope on the SMST. This was characterized by a disproportionate increase in reaction time with increased processing demands (set size), particularly for negative probe trials. In contrast, no significant differences on the SMST were evident between controls and the normal white matter volume TLE group. These findings suggest the presence of information processing speed and efficiency impairment in TLE and its relationship with white matter volume integrity.     

Outcome of lower extremity malignancy survivors treated with transfemoral amputation

OBJECTIVE: To determine outcomes of surviving patients who underwent transfemoral amputation as part of treatment for lower extremity malignancy at a mean 15 years postoperatively, with a minimum 2-year follow-up. DESIGN: Retrospective, case control. SETTING: Tertiary care university medical center. PATIENTS: Thirty-five of 38 consecutively admitted patients free of metastatic disease managed with transfemoral amputation as part of treatment of a lower extremity bone and/or soft tissue malignancy between 1966 and 1997 at 1 institution. The control group included 35 age- and gender-matched subjects recruited from the local driver's license office. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Musculoskeletal Function Assessment (MFA), Short Form-12 General Health Status Survey (SF-12), physical performance battery, cost, and demographic data. RESULTS: Controls showed superior scores as measured by the MFA (P < .0001), the physical component summary of the SF-12 (P = .0002), and the physical performance battery (P < .0001), but had inferior scores on the mental component summary of the SF-12 (P < .0001). With the numbers available, no differences were found between study and control subjects in terms of employment rate (P = .51), education level (P = .66), income level (P =.44), marital status (P = .79), incidence of self-reported health problems (P = .14), and alcohol (P =.42) and tobacco (P = .82) use. Ten patients were included in the cost analysis; the mean cost to obtain and maintain a lower extremity prosthesis was $4225 per year (range, 623 dollars-8517 dollars). CONCLUSIONS: Although the decrease in physical performance was anticipated in the study group, the group differed very little from the control population in terms of employment, education level, income, marital and home status, incidence of self-reported health problems, incidence of self-reported depression, and alcohol and tobacco use. Also, the long-term cost of maintaining a lower extremity prosthesis is noted.     

Development of abnormal tissue architecture in transplanted neonatal rat myocytes

BACKGROUND: Most myocardial cell transplant studies focus on demonstration of improved function; however, such improvement depends on the development of appropriate tissue structure. Thus, our aim was to assess the architectural changes that occurred after cell transplant into normal and infarcted myocardium. METHODS: Male neonatal cells (1 to 2 days old) were injected into the left ventricular free wall of adult female rats. The tissue was examined 0 to 1 days and 1 to 2, 4 to 6, and 12 weeks later in noninfarcted hearts and 6 months after transplant into infarcts. In histologic sections, we assessed the cells' retardation of polarized light (to measure development of contractile elements), two-dimensional cell orientation, cell nuclear morphology, and collagen content. RESULTS: The transplant cells' retardation of polarized light gradually increased to 81% of that of host cells after 6 months (p < 0.001). The transplant cells were disorganized and although their nuclei increased in size, they always had a rounded appearance. Collagen content in the transplant was 210% to 430% higher than in host tissue (p < 0.01). In addition, scar collagen always separated transplant and host cells. CONCLUSIONS: One architectural feature, the rounded nuclei, provided a distinctive marker to identify transplanted cells. Nevertheless, the transplants' inhibited muscle development together with disorganization, separation from the host muscle, and a substantial increase in collagen resulted in a structure unlikely to play an active role in systolic function.     

Designing and facilitating class discussion in an Internet class

Designing a replacement for face-to-face classroom discussion is a major consideration in the development of an Internet course, whether the course is completely new or a redesign of an existing course. The experiences of four faculty members who were involved in developing courses for a baccalaureate completion program for RNs taught entirely on the Internet will be used to illustrate key issues in designing andfacilitating on-line discussion.