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Biomedical subjects

S G Birnbaum

Publications and source records attributed to S G Birnbaum.

8 recordsLinked to original sources
PubMed2004

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

Adrenergic alpha-Agonists↗
PubMed2002

Fluorescent tracer evaluation of chemical protective clothing during pesticide applications in central Florida citrus groves.

Chemical protective clothing (CPC) is often recommended as a method of exposure mitigation among pesticide applicators. This study evaluated four CPC regimens (cotton work shirts and work pants, cotton/polyester coveralls, and two non-woven garments) during 33 airblast applications of the organophosphorus insecticide ethion in central Florida citrus groves. CPC performance was determined by measurement of fluorescent tracer deposition on skin surfaces beneath garments with a video imaging analysis instrument (VITAE system), and by alpha-cellulose patches placed outside and beneath the garments. Non-woven coveralls allowed significantly greater exposure than did traditional woven garments, primarily because of design factors (e.g., large sleeve and neck openings). The greatest exposure occurred on the forearms beneath the non-woven garments. Fabric penetration was detected for all test garments; 5% to 7% of the ethion measured outside the garments was found beneath the garments. The clothing materials tested were not chemically resistant under these field conditions. Exposurepathways that would probably be undetected by the patch technique were characterized effectively with fluorescent tracers and video imaging analysis. However, the patch technique was more sensitive in detecting fabric penetration. CPC garments have been improved since this study was conducted, but performance testing under field conditions is not widespread. Workers conducting airblast applications would be better protected by closed cab systems or any technology that places an effective barrier between the worker and the pesticide spray.

Aerosols↗
PubMed2000

Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats.

Performance on working memory tasks, a measure of prefrontal cortical function, is impaired by exposure to mild stress as well as the anxiogenic drug, FG7142. Previous studies have shown that like stress, FG7142 increases catecholamine release in the prefrontal cortex (PFC) and that high levels of dopamine (DA) D(1) and norepinephrine (NE) alpha-1 receptor stimulation underlie the FG7142-induced cognitive impairment. Both the FG7142-induced DA turnover and working memory deficit can be blocked by pretreatment with the nonselective NE alpha-2/imidazoline I1 receptor agonist, clonidine. The present study examined the alpha-2 adrenoceptor subtype underlying this reversal in FG7142-induced working memory deficits by comparing the efficacy of clonidine with the more selective alpha-2A adrenoceptor agonist, guanfacine. The anxiogenic drug, FG7142 (0, 10, 20, or 30 mg/kg), dose-dependently impaired delayed alternation performance. Clonidine pretreatment (0.1 mg/kg, 30 min prior to FG7142) partially reversed the FG7142-induced impairment while guanfacine pretreatment (0.11 mg/kg) completely blocked the FG7142-induced impairment. Neither clonidine nor guanfacine had any effect on performance when administered alone. This study suggests that stimulation of the NE alpha-2A receptor subtype is sufficient to ameliorate the cognitive deficit induced by FG7142. Clonidine's sedative and hypotensive side effects limit its therapeutic usefulness; however, selective alpha-2A receptor agonists may be effective in treating prefrontal cognitive deficits in stress-related neuropsychiatric disorders with fewer side effects.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1998

Modulation of the acoustic startle reflex by infusion of corticotropin-releasing hormone into the nucleus reticularis pontis caudalis.

The amplitude of the acoustic startle reflex can be modulated by exposure to aversive stimuli or other conditions which evoke a state of fear. The neurotransmitters involved in this modulation are currently being investigated. Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40 and 80 ng) into the nucleus reticularis pontis caudalis (PnC), an obligatory synapse in the acoustic startle reflex, significantly elevated startle amplitude in a dose-dependent manner. The facilitation of startle began immediately following infusion, reached asymptote approximately 20-25 min later, and persisted throughout the remaining 60 min test session. This CRH-enhanced startle effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41, immediately prior to CRH infusion. These results support an involvement of CRH at the level of the PnC in modulating the acoustic startle reflex.

Acoustic Stimulation↗
PubMed1997

Second generation video imaging technique for assessing dermal exposure (VITAE System).

Development of a second-generation video imaging technique for assessing occupational skin exposure (VITAE) is described, its performance evaluated, and new procedures for exposure quantification are presented. The current VITAE system has higher resolution in regard to both its picture element array and gray scale when compared with the prototype system. System performance was evaluated during extended field deployment: variability was 3-4% during data acquisition for individual worker evaluation session, and 10% over a 22-day study period. Variabilities attributable to subject positioning and image outlining procedures were 2.7 and 1.2%, respectively. Visual observations of fluorescent tracer deposition on skin were used to classify specific body regions as either exposed of unexposed, and two computer-based classification criteria were tested against the visual classification. These criteria were generally better at minimizing false negative and false positive classification; sensitivity and predictive value reached 95 and 99%, respectively, when analysis was preceded by presampling of a subset of images. Variability in skin pigmentation was found to have a substantial effect on fluorescent tracer qualification, leading to development of new calibration procedures. Standard curves were generated by spotting a range of tracer concentrations on volunteer subjects and quantifying fluorescence with the VITAE system. These data were then grouped either by subject or by the magnitude of the background signal of the unexposed skin. The ability to control for the effects of skin pigmentation was found to be comparable for these grouping methods, indicating that calibration curves can be developed without the creation of a unique curve for each subject.

Calibration↗
PubMed1988

Quantifying the altered cardiac response to atropine following pyridostigmine in rhesus macaques.

An estimate of the amplitude of respiratory sinus arrhythmia (V) has been proposed as a noninvasive measure of parasympathetic activity. This experiment monitored V in response to a subclinical dose of pyridostigmine bromide (PYR) and a pharmacological challenge of atropine sulfate (ATR). Twelve male rhesus macaques received 200 micrograms/kg of PYR 30 min prior to an injection of 0, 14, 44, or 140 micrograms/kg ATR. The decrease in V after both the 44 and 140 micrograms/kg ATR doses was similar to the response to ATR alone in a previous experiment. The 14 micrograms/kg dose of ATR did not significantly decrease V in this experiment, which is in contrast with the large decrease of V after ATR alone in a previous experiment. Neither drug affected respiration. The dose of ATR which would be effective in causing a 30% decrease of V in the presence of PYR was estimated to be 18.3 micrograms/kg of ATR. This is twice the dose of ATR calculated to have the same effect without PYR. The attenuated response of V after a pharmacological challenge of ATR may be used to quantify the latent muscarinic effects from exposure to anticholinesterase agents. The attenuated response to ATR may also be useful for evaluating the return of normal cholinergic function after disruption by cholinesterase inhibitors.

Animals↗
PubMed1988

Vagal tone monitoring: a potential indicator of anti-cholinesterase exposure in Macaca mulatta.

A vagal tone monitor (VTM) was used to evaluate cardiac rhythm changes in Rhesus monkeys (Macaca mulatta) after intramuscular (i.m.) administration of an anti-cholinergic (atropine sulfate), two carbamates (pyridostigmine bromide and physostigmine salicylate), and combinations of pyridostigmine and atropine. Twelve monkeys were studied in 4 experiments using Latin Square blind designs. Experiment I tested the VTM responses to atropine sulfate injections of 0, 14, 44 and 140 micrograms/kg. Experiment II tested the responses to 0, 100, 200 and 400 micrograms/kg pyridostigmine injections. Experiment III tested the responses to physostigmine injections of 0, 25, 50 and 100 micrograms/kg. Experiment IV tested the same atropine sulfate treatments as Experiment I 30 min after a pyridostigmine pretreatment of 200 micrograms/kg. The VTM analysis produced an estimate of vagal tone (V) every 30 s, and V was averaged over 15 min. The results indicated that V responded more to physostigmine and atropine than pyridostigmine. There was also an attenuated response to atropine following pyridostigmine pretreatment. The attenuated response had been demonstrated earlier in organophosphate (OP) treated dogs. The results suggest that V may be used as a non-invasive indicator of cholinergic drug effects.

Acetylcholinesterase↗