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Functional alterations in the neurotrophin, brain-derived neurotrophic factor (BDNF) have recently been implicated in the pathophysiology of schizophrenia. Furthermore, animal studies have indicated that several antipsychotic drugs have time-dependent (and differential) effects on BDNF levels in the brain. For example, our previous studies in rats indicated that chronic treatment with the conventional antipsychotic, haloperidol, was associated with decreases in BDNF (and other neurotrophins) in the brain as well as deficits in cognitive function (an especially important consideration for the therapeutics of schizophrenia). Additional studies indicate that haloperidol has other deleterious effects on the brain (eg increased apoptosis). Despite such limitations, haloperidol remains one of the more commonly prescribed antipsychotic agents worldwide due to its efficacy for the positive symptoms of schizophrenia and its low cost. Interestingly, the hematopoietic hormone, erythropoietin, in its recombinant human form rhEPO has been reported to increase the expression of BDNF in neuronal tissues and to have neuroprotective effects. Such observations provided the impetus for us to investigate in the present study whether co-treatment of rhEPO with haloperidol could sustain the normal levels of BDNF in vivo in rats and in vitro in cortical neuronal cultures and further, whether BDNF could prevent haloperidol-induced apoptosis through the regulation of key apoptotic/antiapoptotic markers. The results indicated that rhEPO prevented the haloperidol-induced reduction in BDNF in both in vivo and in vitro experimental conditions. The sustained levels of BDNF in rats with rhEPO prevented the haloperidol-induced increase in caspase-3 (p<0.05) and decrease in Bcl-xl (p<0.01) protein levels. Similarly, in vitro experiments showed that rhEPO prevented (p<0.001) the haloperidol-induced neuronal cell death as well as the decrease in Bcl-xl levels (p<0.01). These findings may have significant implications for the development of neuroprotective strategies to improve clinical outcomes when antipsychotic drugs are used chronically.Neuropsychopharmacology (2008) 33, 1942–1951; doi:10.1038/sj.npp.1301566; published online 5 September 2007 [ABSTRACT FROM AUTHOR]

Presents a study that evaluated the selective serotonin receptor antagonist 7-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl}-1H-indole-3-carbonitrile HCl in young and aged rhesus monkeys in a test designed to assess working memory function. Methods; Results; Conclusions.

The ability of choline to serve as a full, though low potency agonist for the α7 nicotinic receptor has provided the impetus to develop analogs that exhibit levels of potency and effectiveness suitable for use as therapeutic agents. Seven analogs of choline were synthesized based on previous work with the analog pyrrolidinecholine. The drugs were administered to differentiated PC-12 cells 24 hr prior to growth factor withdrawal which itself induced cytotoxicity in 30–40% of the cells. Three of 7 choline analogs exhibited potency and efficacy similar to that for nicotine as cytoprotective agents. Despite being tertiary amines, 4 of the choline analogs were more potent than choline in inhibiting [^3H]choline uptake into cultured fibroblasts transfected with the high affinity, sodium-dependent choline transporter. One of the most effective analogs JAY 2-21-29 was shown to produce a potent (EC50 ∼ 30 nM) cytoprotective action that was blocked by pretreatment with the α7 nicotinic receptor selective antagonist methyllycaconitine, but not by theα2 subtype-preferring antagonist dihydro-β-erythroidin. These preliminary studies support the further neurochemical characterization of these compounds 1) as selectiveα7 nicotinic receptor agonists and, 2) based on their interaction with the choline transporter, as potential cholinergic false neurotransmitters as has been demonstrated for pyrrolidinecholine. [ABSTRACT FROM AUTHOR]

In 1993–1994, researchers at Oak Ridge National Laboratory collected high-resolution airborne geophysical data on the Oak Ridge Reservation, Oak Ridge, TN. The data were collected in part to address concerns about possible undocumented hazardous waste sites. Interpretation of the aeromagnetic data was complicated, however, by the discovery in remote areas of numerous small magnetic anomalies of natural origin. Magnetic susceptibility measurements of core showed that the underlying Copper Ridge Dolomite was non-magnetic. We attribute the magnetic anomalies to the presence of the ferromagnetic mineral maghemite (γ-Fe2O3), which formed during pedogenesis of Fe-enriched colluvium that had infilled low-lying areas, including dolines. We discuss explanations offered in the literature for the formation of magnetic soils, and present evidence based on profile descriptions, thin sections, x-ray diffraction (XRD), and scanning electron microscopy (SEM), that in this case, maghemite formed either by anaerobic microbial Fe reduction followed by the formation of single-domain maghemite, or by abiological weathering and reduction of an Fe-bearing mineral followed by oxidation. Naturally occurring magnetic soils may produce magnetic anomalies similar to those characteristics of anthropogenic objects, such as buried waste drums, and complicate interpretation of airborne geophysical surveys. [ABSTRACT FROM AUTHOR]

The rare earth element (REE) content of fossil bones was analyzed and compared with the degree of ancient pedogenic development and depositional environments from several locations in the Orellan Scenic Member of the Oligocene Brule Formation in Badlands National Park, South Dakota. Paleosols ranged from weakly developed Entisols to more strongly developed Inceptisols, all typical of fluvial environments and possible paleocatena variation. Paleosols were alkaline and well drained. Sediments with sparse soil features from an oxbow lake system suggest that conditions were too waterlogged and sedimentation rates too rapid for significant pedogenesis. The variance of REE signatures in fossil bones from the paleosol sites was significantly greater than that of fossils from minimally altered sediments of the former oxbow lake. Positive Ce anomalies were associated with low U concentrations and indicate paleoredox conditions. Greater degrees of pedogenesis, regardless of the horizon in which the bone was found, systematically correlated with increased heavy REE enrichment in fossil bones. The fossil-bone REE signatures from the different paleosols and depositional environments were significantly different and distinguishable. [ABSTRACT FROM AUTHOR]

Discusses the legal and financial issues surrounding the valuation of early stage companies in the context of a marital dissolution. Concept of real options; Venture capital method of valuing early stage companies; Effect of transfer restrictions on value.

Tunable diode laser absorption spectroscopy is used to monitor hydrogen chloride (HCl) concentration in a commercial, high-density, low-pressure plasma reactor during plasma etching. A near-infrared diode laser is used to scan the P(4) transition in the first overtone of HCl near 1.79 µm to measure changes in HCl levels. A variety of HBr and Cl2 feedstock recipes are investigated at a process pressure of 10 mTorr as a function of rf power transformer coupled plasma, bias power and the total flow rate. Using 50 ms averaging and a signal modulation technique, we estimate a minimum detectivity of 4 × 10-6 in peak absorbance, which corresponds to an HCl number density of ~2 × 1011 cm-3. The diode-laser based HCl sensor is sufficiently sensitive to detect small concentration variations and HCl concentration correlates with poly-Si etch rate for the conditions studied. These measurements demonstrate the feasibility of a real-time diode laser-based sensor for etch rate monitoring and the potential for process control. [ABSTRACT FROM AUTHOR]

(N-propargyl-(3R)-aminoindan-5-yl)-ethyl, methyl carbamate (TV3326), a known neuroprotective agent exhibiting the properties of both an inhibitor of monoamine oxidase (brain selective) and an inhibitor of acetylcholinesterase was administered to seven old rhesus monkeys well trained to perform versions of a delayed matching-to-sample (DMTS) task. An increasing dose regimen of TV3326 was administered orally according to a schedule that allowed the animals to perform the standard DMTS task and a self-titrating version of the DMTS task each week during the study. A distractor version of the task was administered during two of the doses of TV3326. Under the conditions of this experiment TV3326 failed to significantly affect accuracy on the standard DMTS task; however, the drug was very effective in improving the ability of subjects to titrate to longer-duration delay intervals in the titrating version of the task. The maximal drug-induced extension of the self-titrated delay interval amounted to a 36.7% increase above baseline. This increase in maximum delay duration occurred without a significant change in overall task accuracy. TV3326 also significantly improved task accuracy during distractor (interference) sessions. The compound was effective enough to return group performance efficiency to standard DMTS vehicle levels of accuracy. These results were independent of whether trials were associated with a distractor or non-distractor delay interval, and they were independent of delay interval. The lack of delay selectivity in task improvement by TV3326 may not be consistent with a selective effect on attention. TV3326 was not associated with any obvious side effect or untoward reaction of the animals to the drug. Thus, TV3326 may be expected to offer a significant positive cognitive outcome in addition to its reported neuroprotective action. [Copyright &y& Elsevier]

Cotinine is a primary metabolite of nicotine that has been suggested in many studies in animals and in humans to exert measurable effects on aspects of on-going behavior or on cognitive function. Much of the interest in cotinine derives from its long pharmacological half-life (15–19 hours) relative to nicotine (2–3 hours). Despite decades of study focusing on nicotine as the predominant behaviorally active component of tobacco, there continue to be aspects of the pharmacology of the drug that have yet to be explained. For example, nicotine can evoke a protracted behavioral response, i.e., in great excess of the presence of the drug in the plasma. Also, there is often a striking differential between the potency for nicotine-induced behavioral responses in humans and animals, and its potency as a cholinergic agonist, neurochemically. One possibility that may explain one or more of these properties of nicotine is the presence of a long-lived bioactive metabolite or breakdown product of nicotine such as cotinine. Preliminary data in support of this hypothesis are consistent with the ability of cotinine to improve performance accuracy on delayed matching task by macaque monkeys, and in reversing apomorphine-induced deficits in prepulse inhibition of acoustic startle in rats. The drug also was shown to be as potent as nicotine in the ability to act as a cytoprotective agent in cells that express a neuronal cholinergic phenotype. This new appreciation for the role of cotinine in nicotine''s actions, and as a pharmacological agent in its own right, particularly in aspects of cognitive function and for neuroprotection, ultimately may be applied towards the treatment of Alzheimer''s disease and related disorders, and for various psychiatric syndromes. [Copyright &y& Elsevier]

Objective: The spontaneously hypertensive rat (SHR), often used to study cardiovascular disease processes, may also be utilized to model certain central nervous system changes associated with memory disorders. Previous work in our laboratory indicated that central nicotinic acetylcholine receptors are markedly diminished and that memory-related task performance is impaired in this rodent phenotype. Due to the well-documented importance of the central cholinergic system to memory processes and its vulnerability to the effects of aging, it was of interest to measure other cholinergic markers and to further evaluate memory function in older SHRs. Method: Radial arm maze performance was used to assess working memory, quantitative receptor autoradiography with [³H]-pirenzipine, [³H]-AFDX-384 and [³H]epibatidine (combined with cytisine) was used to determine the densities of muscarinic-MI and -M2 and nicotinic cholinergic α3 receptors, respectively. Immunoblotting experiments were also used to determine the expression of the presynaptic cholinergic markers, choline acetyltransferase and the vesicular acetylcholine transporter. Results: Radial arm maze performance was impaired in hypertensive (compared with normotensive Wistar and Wistar-Kyoto) rats, regardless of age. MI binding was increased in frontal and prefrontal cortical areas in SHR (p < 0.05), whereas M2 densities were higher in the hypertensive phenotype in the caudate putamen. A lower expression of α3-containing nicotinic receptors was observed in the superior colliculus in SHRs. Age-related differences in the expression of the vesicular acetylcholine transporter were noted in the hippocampus. Conclusion: The SHR may be useful to model some aspects (particularly hypertension-related) of memory disorders, especially those in which cholinergic function is altered. [ABSTRACT FROM AUTHOR]

Haloperidol (HAL), a potent typical antipsychotic, continues to be a frequently prescribed medication for behavioral disturbances associated particularly with schizophrenia despite well-documented adverse effects associated with its chronic use. Animal experiments have even indicated that HAL can damage cholinergic pathways and thus could be especially deleterious to those experiencing cognitive deficits. However, several recent clinical studies indicate that atypical antipsychotics may actually improve cognitive function in some patients, although this assertion requires further investigation. The purpose of this study was to compare the effects of prior chronic (45-or 90-day) oral exposure to HAL and the atypical antipsychotics risperidone (RISP) and clozapine (CLOZ) on cognitive performance and central cholinergic markers in rats. All analyses were done after 4 days of drug washout in order to minimize direct drug effects. Learning performance and choline acetyltransferase (ChAT) levels were assessed in a water maze task and with immunofluorescence staining, respectively. HAL significantly impaired learning performance after 90 but not after 45 days of treatment when compared to both vehicle controls and the atypical agents, while RISP slightly improved task performance. Both 45 and 90 days of previous HAL exposure reduced ChAT staining in several brain regions, including the cortex, caudate-putamen, and hippocampus. ChAT staining in the caudate-putamen and hippocampus was also decreased after 90 days of RISP exposure, raising the possibility of deleterious cognitive effects after exposure to this dosage for longer periods of time. The results suggest that antipsychotic drugs exert differential and temporally dependent effects on central cholinergic neurons and learning performance. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the accuracy of algorithms for the assignment of gestational age with the use of the last menstrual period and early ultrasound information.Study Design: Gestational age estimates that are based on last menstrual period, ultrasound scanning, or their combination were compared among women who attended prenatal care clinics in central North Carolina (n = 3655) by an evaluation of digit preference in the last menstrual period dates and a comparison of mean gestational age, preterm and postterm categories with the use of kappa statistics, difference between actual and expected delivery date, and birth weight among subgroups with discrepant assignments.Results: Last menstrual period reports show digit preference, assign gestation 2.8 days longer on average than ultrasound scanning, yield substantially more postterm births (12.1% vs 3.4%), and predict delivery among term births less accurately. Misclassification of births as postterm was more common in younger women, those of nonoptimal prepregnancy body weight, cigarette smokers, and women who reported last menstrual period using preferred dates of the month.Conclusion: Last menstrual period estimates of the duration of gestation are subject to both random error and a systematic tendency to overstate the duration of gestation, most likely because of delayed ovulation. [ABSTRACT FROM AUTHOR]

Focuses on the evolution of the Electronic Laboratory Surveillance System (ELS) from a limited system to one that can play a role in identifying and linking bioterrorism events. Original design concept of the ELS; Description of the Electronic Disease Reporting System and the Electronic Disease Reporting and Management System.

Impairment in nerve growth factor (NGF)-mediated support to basal forebrain cholinergic neurons may represent an initial insult to certain neural cells in Alzheimer''s disease (AD). High affinity NGF receptor (TrkA) levels are decreased in AD brains as compared to age-matched control brains. One of the approaches suggested for the treatment of AD exploits the ability of small molecular substances to enhance the expression of endogenous growth factors and/or their receptors. The purpose of this study was to determine whether treatment with nicotine in both in vitro and in vivo settings would increase the neural expression of TrkA receptors. Using a differentiated PC12 neuronal-like system, chronic nicotine treatment increased cell surface TrkA receptor expression. Nicotine''s action was blocked by co-treatment with either the non-competitive nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine or with the α7 nAChR-selective antagonist methyllycaconitine. Surprisingly, certain low doses of mecamylamine alone also increased TrkA receptor levels. Rats prepared with chronic indwelling intravenous catheters were continuously infused with nicotine to deliver a total dose of 12 mg/kg over 24 hr. This treatment resulted in a significant 44% increase in TrkA receptor expression in the hippocampus. As in the cell experiments, mecamylamine also increased hippocampal TrkA receptor expression. In fact, the ratio of the maximal mecamylamine response to the maximal nicotine response that was measured in vitro, i.e., 0.43 was remarkably similar to that for the in vivo experiment, i.e., 0.47. Since in our previous studies the increase in TrkA expression produced by nicotine was shown to be related to its cytoprotective actions, these results suggest that nicotine''s neuroprotective actions might also be mediated through the drug''s interaction with central α7 nAChRs and subsequent increase in TrkA receptor expression. [Copyright &y& Elsevier]

Examines the marine Cretaceous-Tertiary (K-T) boundary section in South Dakota. Physical description the disrupted zone; Identification of the K-T boundary sections within terrestrial facies; Area covered by the Western Interior Seaway.

Investigates the etch profile control of high-aspect ratio deep submicrometer. Focus on the control of transition timing in the critical interval from main etch to over etch; Utilization of Kalman-Bucy filter with a real-time spectroscopic ellipsometer; Application of endpoint detection technique.

The article discusses management training and development efforts of Multinational Corporations, that plan to enter into ventures with organizations. The joint U.S.-Hungarian team identified nine key functions that enterprise managers must master to be internationally competitive: Establish and monitor mission, strategies, action plans, and policies; Understand industry, government, political, economic, social, regulatory and labor environments; Develop short and long-range manufacturing plans and procedures, including capital investments. Among national and international development agencies, management training ranks high on every list of priority needs. For the designers of such programs, 12 principles or guidelines stand out. Development programs must have top-level support, not only within companies but also by government and professional bodies; Management education should cascade downward, with CEOs the first to sponsor, fund, and join in; Participation has to be self-motivated, both on company and individual levels; For the highest levels of executives, particularly, training programs will be most credible if presented by executives with comparable responsibilities and with success in international commerce.

The chemicals known as the organophosphates (OPs) are found in hundreds of useful agricultural, industrial, and commercial products; however, they have also been associated with a variety of adverse health effects in humans and other non-target organisms. The acute toxicity of OPs is attributed to the inhibition of the enzyme acetylcholinesterase; however, this mechanism is inadequate to explain all of the long-term adverse effects of OPs. In both live imaging studies in primary neuronal culture as well as in manganese-enhanced magnetic resonance imaging (MEMRI) studies of the brains of living rats, we have observed impairments in axonal transport (AXT) associated with both the insecticide OP chlorpyrifos and the nerve agent OP diisopropylfluorophosphate. These observations may be important since AXT is an essential process that is responsible for the movement of a variety of important macromolecules to and from a neuron's cell body. In this presentation, a brief overview of the results of these neuronal culture (trafficking) and MEMRI experiments will be provided. In addition, the results of experiments conducted to date to identify specific molecular targets of OPs that might negatively influence axonal transport will be summarized. These targets include post-translational modifications of structural proteins that affect AXT through the regulation of microtubule dynamics and stability (e.g., Tau phosphorylation, Tubulin Acetylation), and specific signaling kinases (e.g., ERK GSKIIIß) that are known to regulate various components of the AXT process. These experiments are expected to help us begin to develop novel therapeutic strategies to improve the neuronal deficits associated with OPs. [ABSTRACT FROM AUTHOR]

Presents the reply on the comment on marine cretaceous-tertiary (K-T) boundary section in southwestern South Dakota. Differences in the physical expression of K-T boundary interval in the distal deltaic area; Occurrence of the molluscan species in the Maastrichtian; Limitation of the Hell Creek Formation.

Investigates the hydrogen sulfide plasma passivation of gallium arsenide. Advantages of the plasma sulfidation over conventional wet chemical treatments; Components of the photoluminescence analysis; Techniques used for the sulfidation of the GaAs surface.