Rat Serum Contains a Developmentally Regulated Cholinergic Inducing Activity

Sympathetic neurons cultured in defined medium do not develop the ability to produce acetylcholine, as do neurons grown with serum supplementation (lacovitti, L., M. I. Johnson, T. H. Joh, and R. P. Bunge (1982) Neuroscience 7:2225–2239; Wolinsky, E. J., S. C. Landis, and P. H. Patterson (1985) J. Neurosci. 5: 1497–1508). The implication that rat serum contains cholinergic inducing activity is further explored here. Dependence of cholinergic induction on serum concentration is demonstrated, and the activity is shown to reside in a macromolecular fraction. Very little cholinergic inducing activity is present in serum obtained from animals younger than 9 postnatal days. This age dependence correlates with the time of transition from noradrenergic to cholinergic transmitter status by the sympathetic innervation of the rat sweat gland in vivo (Landis, S. C., and D. Keefe (1983) Dev. Biol. 98: 349–372)

Emergency Department Pain Management Following Implementation of a Geriatric Hip Fracture Program

Introduction: Over 300,000 patients in the United States sustain low-trauma fragility hip fractures annually. Multidisciplinary geriatric fracture programs (GFP) including early, multimodal pain management reduce morbidity and mortality. Our overall goal was to determine the effects of a GFP on the emergency department (ED) pain management of geriatric fragility hip fractures. Methods: We performed a retrospective study including patients age ≥65 years with fragility hip fractures two years before and two years after the implementation of the GFP. Outcomes were time to (any) first analgesic, use of acetaminophen and fascia iliaca compartment block (FICB) in the ED, and amount of opioid medication administered in the first 24 hours. We used permutation tests to evaluate differences in ED pain management following GFP implementation. Results: We studied 131 patients in the pre-GFP period and 177 patients in the post-GFP period. In the post-GFP period, more patients received FICB (6% vs. 60%; difference 54%, 95% confidence interval [CI] 45–63%; p<0.001) and acetaminophen (10% vs. 51%; difference 41%, 95% CI 32–51%; p<0.001) in the ED. Patients in the post-GFP period also had a shorter time to first analgesic (103 vs. 93 minutes; p=0.04) and received fewer morphine equivalents in the first 24 hours (15mg vs. 10mg, p<0.001) than patients in the pre-GFP period. Conclusion: Implementation of a GFP was associated with improved ED pain management for geriatric patients with fragility hip fractures. Future studies should evaluate the effects of these changes in pain management on longer-term outcomes

Insulin Promotes Electrical Coupling between Cultured Sympathetic Neurons

Placing neurons in tissue culture is one way to study how environmental factors affect their differentiation. Replacement of serum- supplementation of the culture medium with defined ingredients extends the experimenter's control of the culture environment; however it also introduces additional potential influences. In this report, we confirm the observation of Higgins and Burton (Higgins, D., and H. Burton (1982) Neuroscience 7:2241–2253) of increased frequency of electrical coupling in serum-free compared to serum-supplemented cultures of rat sympathetic neurons. In addition, experiments were performed to determine whether this effect results from the removal of serum or from the addition of the defined medium components to the culture environment. The results of testing individual ingredients of the defined medium recipe adapted for use on sympathetic neurons (Bottenstein, J.E., and G. H. Sato (1979) Proc. Natl. Acad. Sci. U. S. A. 76:514–517) show that insulin is capable of inducing electrical coupling in serum-free cultures. Thus, the formation of electrical synapses by sympathetic neurons can be hormonally regulated

Expression of Noradrenergic and Cholinergic Traits by Sympathetic Neurons Cultured without Serum

The ability to vary systematically the neuronal environment is one advantage afforded by the use of cell culture. Replacement of serum, a variable and undefined medium supplement, with known ingredients allows even greater control of culture conditions. We have studied biochemical and morphological properties related to neurotransmitter metabolism of rat sympathetic neurons cultured in a modified defined medium. Neuronal survival, ultrastructure, and expression of noradrenergic properties appear similar in serum-free and serum-supplemented cultures: small granular vesicles characteristic of norepinephrine storage were observed in both types of culture, and tyrosine hydroxylase activity, conversion of dopamine to norepinephrine, catecholamine production, and storage capacity are equivalent in serum-free and serum-containing cultures. Several of these properties were not exhibited at high levels in previous formulations of this defined medium. Acetylcholine production, however, was about 10-fold lower in serum-free compared to serum-supplemented cultures, consistent with the findings of lacovitti et al. (lacovitti, L., M. I. Johnson, T. H. Joh, and R. P. Bunge (1982) Neuroscience 7:2225–2239). Acetylcholine production can be induced under serum-free conditions by a previously characterized cholinergic inducing factor from heart cell conditioned medium. This responsiveness to serum-free heart cell conditioned medium indicates that serum-free cultures retain plasticity with respect to transmitter status, despite expression of noradrenergic characteristics, unlike cultured neurons of which the noradrenergic transmitter status is maintained by chronic depolarization. Thus, sympathetic neurons survive, express numerous differentiated properties, and display a novel transmitter status under serum-free conditions

Progress Towards the Development of a Traveling Wave Direct Energy Converter for Aneutronic Fusion Propulsion Applications

A coordinated experimental and theory/simulation effort has been carried out to investigate the physics of the Traveling Wave Direct Energy Converter (TWDEC), a scheme that has been proposed in the past for the direct conversion into electricity of the kinetic energy of an ion beam generated from fusion reactions. This effort has been focused in particular on the TWDEC process in the high density beam regime, thus accounting for the ion beam expansion due to its space charge

On the informational content of wage offers

This article investigates signaling and screening roles of wage offers in a single-play matching model with two-sided unobservable characteristics. It generates the following predictions as matching equilibrium outcomes: (i) “good” jobs offer premia if “high-quality” worker population is large; (ii) “bad” jobs pay compensating differentials if the proportion of “good” jobs to “low-quality” workers is large; (iii) all firms may offer a pooling wage in markets dominated by “high-quality” workers and firms; or (iv) Gresham’s Law prevails: “good” types withdraw if “bad” types dominate the population. The screening/signaling motive thus has the potential of explaining a variety of wage patterns

Tyrosine hydroxylase activity decreases with induction of cholinergic properties in cultured sympathetic neurons

Establishment of transmitter phenotype is an essential step in neuronal development. Studies on rat sympathetic neurons both in vivo and in vitro have provided evidence that mature cholinergic sympathetic neurons arise from previously noradrenergic neurons. Cultured rat superior cervical ganglion neurons can be influenced by their environment to remain noradrenergic, to acquire dual transmitter function, or to become predominantly cholinergic. Several other neuronal traits, such as a variety of surface molecules and released proteins, change simultaneously with levels of catecholamine and acetylcholine production, suggesting that various components of transmitter phenotype are regulated in concert. In this report, tyrosine hydroxylase levels are compared in neurons cultured under noradrenergic, dual function, or cholinergic conditions. Both enzyme activity in cell extracts and immunocytochemical staining were measured. These methods showed significantly less tyrosine hydroxylase enzyme activity and immunoreactive material in cholinergic cultures compared to noradrenergic and dual function cultures. These data support the interpretation that a switch in transmitter status from noradrenergic to cholinergic has occurred. This interpretation contrasts with that of Iacovitti et al. (Iacovitti, L., T. H. Joh, D. H. Park, and R. P. Bunge (1981) J. Neurosci. 1: 685–690), who conducted their experiments under critically different culture conditions

Rat Serum Contains a Developmentally Regulated Cholinergic Inducing Activity

Sympathetic neurons cultured in defined medium do not develop the ability to produce acetylcholine, as do neurons grown with serum supplementation (lacovitti, L., M. I. Johnson, T. H. Joh, and R. P. Bunge (1982) Neuroscience 7:2225–2239; Wolinsky, E. J., S. C. Landis, and P. H. Patterson (1985) J. Neurosci. 5: 1497–1508). The implication that rat serum contains cholinergic inducing activity is further explored here. Dependence of cholinergic induction on serum concentration is demonstrated, and the activity is shown to reside in a macromolecular fraction. Very little cholinergic inducing activity is present in serum obtained from animals younger than 9 postnatal days. This age dependence correlates with the time of transition from noradrenergic to cholinergic transmitter status by the sympathetic innervation of the rat sweat gland in vivo (Landis, S. C., and D. Keefe (1983) Dev. Biol. 98: 349–372)