AGE-RELATED ALTERATIONS IN THE DYNAMICS OF L-GLUTAMATE REGULATION IN THE STRIATUM OF THE FISCHER 344 RAT

L-glutamate is the predominant excitatory amino acid neurotransmitter inthe mammalian central nervous system. Prior aging studies have focusedprimarily on dopaminergic circuitry of the striatum, and data obtained studyingglutamate regulation in the striatum have been largely equivocal. Thesediscrepancies are due in large part to the limitations of microdialysis; while it isextremely sensitive to minute concentrations of analyte, it is lacking in terms ofthe temporal resolution necessary to study a neurotransmitter with rapid releaseand clearance kinetics such as glutamate. In order to address this matter, ourlaboratory has designed a ceramic-based multisite microelectrode with thecapability to detect and analyze fluctuations in extracellular glutamateconcentrations on a sub-second basis. These microelectrodes were utilized tostudy the phasic release and uptake dynamics of potassium-evoked glutamate inthe striatum of young (6 month), late-middle aged (18 month) and aged (24month) Fischer 344 rats. Our results showed a reduced glutamate clearancerate and an attenuated response to potassium depolarization in the corticostriatalprojections of aged animals in comparison to other age groups. In addition,average maximal glutamate release amplitudes were decreased in the striatumof aged animals. Pressure ejection of exogenous glutamate solution furtherconfirmed the decreased glutamate clearance ability of the aged striatum. Thesepotassium and exogenous glutamate data also highlighted a markeddorsoventral gradient in the striatum in terms of glutamate release and clearanceability. We further explored this phenomenon of age-related decreased glutamateuptake by coupling our in vivo technology with classical immunoblotting andbiotinylation techniques in order to investigate glutamate transporter regulation.Decreased glutamate clearance in the aged rats cannot be attributed to areduction in steady-state total transporter protein levels. Rather, our resultsindicate that reduced plasma membrane surface trafficking of GLAST in the agedstriatum may be partially responsible for this effect. Finally, we modified ourmicroelectrodes to study basal glutamate levels in the striatum of the aging,freely moving rat. This approach allowed us to study extracellular glutamateregulation free from the potential confounding variable of anesthesia. Our resultsdemonstrate that there is no significant alteration in basal glutamate levels inaging in the brain regions investigated. More importantly, this study validated theefficacy of the utilization of ceramic-based multisite microelectrodes for the studyof alterations in glutamate neurotransmission in the aging, freely moving rat, andit lays the foundation for future work correlating such changes with age associatedimpairments in motor function

[Bibliography of \u3cem\u3eMissing Pieces: How to Investigate Ghosts, UFOs, Psychics, & Other Mysteries\u3c/em\u3e] Part 2: Reference Sources for the Investigator

This is a list of major reference works representing important information sources for the investigator of ghosts, UFOs, psychics, and other mysteries

Vesicular Monoamine Transporter-2 Ligands and Their Use in the Treatment of Psychostimulant Abuse

The present invention relates to methods of treatment of a disease or pathology of the central nervous system, an eating disorder, or substance use disorder, drug dependence/abuse and withdrawal therefrom comprising administering at least one N-phenylalkyl amphetamine derivative and pharmaceutical compositions comprising at least one N-phenylalkyl amphetamine derivative to an individual in need thereof

ASME code ductile failure criteria for impulsively loaded pressure vessels

Ductile failure criteria suitable for application to impulsively loaded high pressure vessels that are designed to the rules of the ASME Code Section VI11 Division 3 are described and justified. The criteria are based upon prevention of load instability and the associated global failure mechanisms, and on protection against progressive distortion for multiple-use vessels. The criteria are demonstrated by the design and analysis of vessels that contain high explosive charges

Bis(\u3cem\u3eN\u3c/em\u3e-amidinohydrazones) and \u3cem\u3eN\u3c/em\u3e-(amidino)-\u3cem\u3eN\u3c/em\u3e\u27-aryl-bishydrazones: New Classes of Antibacterial/Antifungal Agents

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicr obial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N\u27-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step, resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of the tested strains with minimum inhibitory concentration (MIC) values ranging from \u3c 0.5- \u3e 500 μM against bacteria and 1.0- \u3e 31.3 μg/mL against fungi; and in most cases, they exhibited either superior or similar antimicrobial activity compared to those of the standard drugs used in the clinic. We also observed minimal emergence of drug resistance to these newly synthesized compounds by bacteria and fungi even after 15 passages, and we found weak to moderate inhibition of the human Ether-à-go-go-related gene (hERG) channel with acceptable IC50 values ranging from 1.12-3.29 μM. Overall, these studies sh ow that bis(N-amidinohydrazones) and N-(amidino)-N\u27-aryl-bishydrazones are potentially promising scaffolds for the discovery of novel antibacterial and antifungal agents

Actionable Patient Safety Solution (APSS) #3B: Improve Prevention of Severe Hypoglycemia

Severe hypoglycemia (SH) causes significant morbidity and occasional mortality in hospitalized patients. The establishment of an effective program to reduce errors in the recognition and treatment of SH requires an implementation plan that includes the following actionable steps[.

The lowa farmer and world war II

World War II is the biggest fact in the Iowa farm situation. Though Iowa is far removed from air bombing and submarine torpedoing, it is on the battle front so far as economic and social effects of the war are concerned. Iowa’s commercial agriculture underwent terrific strain during and following World War I, and the pressures arising out of World War II promise to be similar, although less severe. It is the purpose of this report to estimate what some of these pressures will be. An understanding of the social and economic forces at work is necessary before plans can be made and action taken to ease the shock of war. The experience of the earlier war helps us to understand these forces, but that experience must be interpreted in light of the changed situation today

Actionable Patient Safety Solutions (APSS) #3A: Medication Errors

A medication error is a preventable event in any healthcare setting that may lead to inappropriate medication use while in the control of the healthcare professional or patient, ultimately leading to patient harm and/or death. Medication errors can be classified into five categories: 1) wrong drug, 2) wrong dose, 3) wrong route, 4) wrong frequency and/or 5) wrong patient