Edward B. Truitt

Bio: Edward B. Truitt is an academic researcher from Wake Forest University. The author has contributed to research in topics: Inotrope & Molecular orbital theory. The author has an hindex of 8, co-authored 17 publications receiving 389 citations.

Determination of salicylic acid and two metabolites in plasma and urine using fluorimetry for directly measuring salicyluric acid.

Abstract: An improved method has been developed for the measurement of salicylic acid and salicyluric acid in blood plasma and for these two substances and salicyl glycuronates in urine. Older methods measured salicyluric acid by the different extraction efficiencies of two solvents and the weaker color formation of salicyluric acid with ferric nitrate. This method measures salicyluric acid more specifically by means of its marked fluorescence at p H 10. A low concentration of a fluorescent substance, probably salicyluric acid, which has not been reported previously was found in dog plasma following large doses of sodium salicylate. The rate of hydrolysis of salicyluric acid by concentrated hydrochloric acid, an important factor in the calculation of the salicyl glycuronate fraction in this and former methods, has been re-examined and a higher value than previously reported has been found. An explanation of this difference is suggested. A synthetic sample of the glycuronate of salicylic acid coupled through the phenolic hydroxyl group, which has not been isolated from urine in pure form, has been tested for reactivity in the method.

Measurement of brain excitability by use of hexafluorodiethyl ether (indoklon)

Abstract: A simple quantitative test has been described for the measurement of brain seizure thresholds in mice and rats using hexafluorodiethyl ether (HFE). The test is conducted using ordinary laboratory glassware and equipment. Seizure thresholds with undiluted HFE were found to be identical to a 10% HFE-ethanol solution, which was routinely used, when the amounts of actual HFE used were measured. The test is unaffected by temperature variations over the expected range of laboratory room fluctuations. Repeated daily tests in rats do not alter the seizure threshold but do cause an earlier appearance of preconvulsive myoclonic jerks. A comparison of the test has been made to the minimal electroshock threshold (M.E.T.) and the intravenous pentylenetetrazol (PTZ) tests using the responses to four anticonvulsant drugs, phenobarbital sodium, trimethadione, methocarbamol and diphenyihydantoin sodium. The HFE anticonvulsant parameters were found to resemble those of the PTZ test much more closely than for the M.E.T. type of electroshock test. Diphenyihydantoin produced similar anticonvulsant activity in all three tests, but was weak and irregular in action. The myoclonic jerks preceding the HFE and PTZ convulsions were more resistant to alteration by all four anticonvulsants than were the seizure thresholds. The relative merits of the three tests are compared and it is concluded that the HFE test offers a convenient substitute for the PTZ with many inherent advantages.

Sympathomimetic effects of acetaldehyde on the electrical and contractile characteristics of isolated left atria of guinea pigs

Abstract: Acetaldehyde (CH3CHO), a major metabolite of ethanol, has been postulated to be an indirect-acting sympathomimetic agent. This hypothesis was tested in vitro on the electrically driven left atria of guinea pigs. Simultaneous recordings of transmembrane potentials and isometric contractions were made. CH3CHO (0.1-30 mM) induced a dose-related biphasic response in the contractile force of the atrium. Low concentrations (0.3-3 mM) induced positive inotropic responses, whereas high concentrations (10-30 mM) induced negative inotropic responses and arrhythmias. Pretreatment with reserpine inhibited the positive inotropic effects induced by CH3CHO without altering the negative inotropic responses. Propranolol inhibited all inotropic responses induced by CH3CHO. Low concentrations of CH3CHO induced changes in the action potential similar to those seen with norepinephrine or tyramine. it was concluded that CH3CHO induced positive inotropic responses through indirect sympathetic mechanisms and a depression through a direct effect on myocardial tissue.

The preferred conformation of dopamine from molecular orbital theory

Abstract: The preferred conformation of dopamine derived from molecular orbital theory calculations predicts that it differs from the previously calculated pattern for norepinephrine. This difference, coupled with known variations in the activity of these agonists, supports the concept of separate receptors for the two molecules.

Acetaldehyde mediation in the mechanism of ethanol-induced changes in norepinephrine metabolism.

Abstract: The role of acetaldehyde in reducing the oxidative pathway and increasing the reductive route for norepinephrine (NE) metabolism was evaluated. Experiments were performed in which 14 C-NE was injected into rats and its metabolic fate in vivo was monitored in the urine. Ethanol administration failed to alter the biochemical disposition of this amine, whereas, acetaldehyde produced profound aberrations in NE metabolism. The excretion of 14 C-vanillylmandelic acid and dihydroxymandelic acid was decreased as a result of treatment with acetaldehyde, disulfiram, or calcium carbimide. A concomitant increase in labeled 3-methoxy-4-hydroxyphenylglycol was also observed with these treatments. Administration of ethanol to animals previously treated with disulfiram or calcium carbimide potentiated this effect and resulted in elevated acetaldehyde blood levels as measured by a specific gas chromatographic procedure. These findings confirm the hypothesis that competitive inhibition of aldehyde dehydrogenase by acetaldehyde is the quantitatively important mechansim in the genesis of altered neuroamine metabolism by ethanol.

Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine

Abstract: This article provides an update about catecholamine metabolism, with emphasis on correcting common misconceptions relevant to catecholamine systems in health and disease. Importantly, most metabolism of catecholamines takes place within the same cells where the amines are synthesized. This mainly occurs secondary to leakage of catecholamines from vesicular stores into the cytoplasm. These stores exist in a highly dynamic equilibrium, with passive outward leakage counterbalanced by inward active transport controlled by vesicular monoamine transporters. In catecholaminergic neurons, the presence of monoamine oxidase leads to formation of reactive catecholaldehydes. Production of these toxic aldehydes depends on the dynamics of vesicular-axoplasmic monoamine exchange and enzyme-catalyzed conversion to nontoxic acids or alcohols. In sympathetic nerves, the aldehyde produced from norepinephrine is converted to 3,4-dihydroxyphenylglycol, not 3,4-dihydroxymandelic acid. Subsequent extraneuronal O-methylation consequently leads to production of 3-methoxy-4-hydroxyphenylglycol, not vanillylmandelic acid. Vanillylmandelic acid is instead formed in the liver by oxidation of 3-methoxy-4-hydroxyphenylglycol catalyzed by alcohol and aldehyde dehydrogenases. Compared to intraneuronal deamination, extraneuronal O-methylation of norepinephrine and epinephrine to metanephrines represent minor pathways of metabolism. The single largest source of metanephrines is the adrenal medulla. Similarly, pheochromocytoma tumor cells produce large amounts of metanephrines from catecholamines leaking from stores. Thus, these metabolites are particularly useful for detecting pheochromocytomas. The large contribution of intraneuronal deamination to catecholamine turnover, and dependence of this on the vesicular-axoplasmic monoamine exchange process, helps explain how synthesis, release, metabolism, turnover, and stores of catecholamines are regulated in a coordinated fashion during stress and in disease states.

Peptides and Peptide Hormones for Molecular Imaging and Disease Diagnosis

Abstract: Molecular imaging techniques are now indispensable tools in modern diagnostics, because they are highly specific and can provide biological information at the molecular level in living systems.1,2 They have enabled visualization of some of the specific molecular events that play key roles in disease processes, and they have enabled earlier diagnosis, as well as monitoring of therapeutic responses. Various imaging modalities, including positron emission tomography (PET), single photon emission computed tomography (SPECT), optical fluorescence imaging, magnetic resonance imaging (MRI), computed tomography, and ultrasound imaging are all successfully employed in the field of molecular imaging. Specific imaging is generally created by contrast agents; however, most current clinical imaging remains at the anatomical and macro functional level, due to the low targeting efficiency of such agents. To support the unmet needs for in vivo clinical molecular imaging, there has been considerable interest in investigating the design of highly sensitive and specific molecularly-targeted imaging probes. To date, a large variety of sophisticated imaging probes have been developed by combining various imaging moieties (i.e., radioisotopes, fluorophores, and nanoparticles) and targeting ligands (i.e., small molecules, peptides, proteins, antibodies, as well as cells). These efforts have profoundly impacted the availability of imaging probes and significantly improved the performance of imaging modalities. Several review articles have discussed recent development and applications of molecular imaging probes2-7, particularly the utilization of peptide- and peptide hormone-based imaging probes. An ideal imaging probe would have high affinity and specificity for the target of interest. However, requirements beyond targeting selectivity become determinants for the suitability of probes for in vivo applications, including in vivo metabolic stability, high target-to-background ratio, rapid clearance from non-target tissues, and safety. Furthermore, tolerance and flexibility towards bulky chemical modification are also needed, because imaging probes are often associated with labeling of radioisotopes, fluorophores, and materials such as linkers, polymers, and metals. From a practical standpoint, synthetic peptides have attracted much attention as molecular imaging probes for small molecules and macromolecules.8-10 Recent advances in phage display technology, combinatorial peptide chemistry, and biology have led to the development of robust strategies for the design of peptides as drugs and biological tools, resulting in identification of a rich variety library of bioactive peptide ligands and substrates.11-13 To date, peptides that target a number of disease-related receptors, biomarkers, and the processes of angiogenesis and apoptosis are in place. These peptides reveal high specificity for their target at nanomolar concentrations and have low toxicity. They can be easily synthesized, modified to optimize their binding affinity, and possibly further modified structurally to improve their stability against proteolytic degradation, to increase half-life in circulation, and to enhance capillary permeability. All of these attributes promote penetration into tissue and more effective targeting. Furthermore, established peptide synthesis processes are easy to scale up, and they yield reproducible products with well-defined structures. With the combination of advanced imaging sciences, peptide chemistry, and the increasing availability of animal imaging instruments, various kinds of highly specific peptide-based imaging probes for different imaging modalities have been designed and validated in preclinical and clinical investigations. In the following review, an overview of molecular imaging probes associated with peptides and peptide hormones designed for in vivo applications, including those for nuclear imaging, optical imaging, and MRI, is provided. For the sake of focus, this article will not discuss imaging probes that have been tested only under in vitro cellular conditions, although many of these can be applied in vivo. Key peptides for selective targeting of biological receptors or biomarkers and modification strategies for these peptides will be summarized. Then, the unique concepts, characteristics, and applications of various peptide-based imaging probes will be discussed for each of several modalities.

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

Abstract: Background : Recent advances in the field of acetaldehyde (AcH) research have raised the need for a comprehensive review on the role of AcH in the actions of alcohol. This update is an attempt to summarize the available AcH research. Methods : The descriptive part of this article covers not only recent research but also the development of the field. Special emphasis is placed on mechanistic analyses, new hypotheses, and conclusions. Results : Elevated AcH during alcohol intoxication causes alcohol sensitivity, which involves vasodilation associated with increased skin temperature, subjective feelings of hotness and facial flushing, increased heart and respiration rate, lowered blood pressure, sensation of dry mouth or throat associated with bronchoconstriction and allergy reactions, nausea and headache, and also reinforcing reactions like euphoria. These effects seem to involve catecholamine, opiate peptide, prostaglandin, histamine, and/or kinin mechanisms. The contribution of AcH to the pathological consequences of chronic alcohol intake is well established for different forms of cancer in the digestive tract and the upper airways. AcH seems to play a role in the etiology of liver cirrhosis. AcH may have a role in other pathological developments, which include brain damage, cardiomyopathy, pancreatitis, and fetal alcohol syndrome. AcH creates both unpleasant aversive reactions that protect against excessive alcohol drinking and euphoric sensations that may reinforce alcohol drinking. The protective effect of AcH may be used in future treatments that involve gene therapy with or without liver transplantation. Conclusions : AcH plays a role in most of the actions of alcohol. The individual variability in these AcH-mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcH-metabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.

Potentially harmful drug-drug interactions in the elderly: a review.

Abstract: Background Elderly patients are vulnerable to drug interactions because of age-related physiologic changes, an increased risk for disease associated with aging, and the consequent increase in medication use. Objective The purpose of this narrative review was to describe findings from rigorously designed observational cohort and case-control studies that have assessed specific drug interactions in elderly patients. Methods The PubMed and International Pharmaceutical Abstracts databases were searched for studies published in English over the past 10 years (December 2000–December 2010) using relevant Medical Subject Headings terms ( aged; aged, 80 and over; and drug interactions ) and search terms ( drug interaction and elderly ). Search strategies were saved and repeated through September 2011 to ensure that the most recent relevant published articles were identified. Additional articles were found using a search of review articles and reference lists of the identified studies. Studies were included if they were observational cohort or case-control studies that reported specific adverse drug interactions, included patients aged ≥65 years, and evaluated clinically meaningful end points. Studies were excluded if they used less rigorous observational designs, assessed pharmacokinetic/pharmacodynamic properties, evaluated drug-nutrient or drug-disease interactions or interactions of drug combinations used for therapeutic benefit (eg, dual antiplatelet therapy), or had inconclusive evidence. Results Seventeen studies met the inclusion criteria. Sixteen studies reported an elevated risk for hospitalization in older adults associated with adverse drug interactions. The drug interactions included: angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics, ACE inhibitors or angiotensin receptor blockers and sulfamethoxazole/trimethoprim, benzodiazepines or zolpidem and interacting medications, calcium channel blockers and macrolide antibiotics, digoxin and macrolide antibiotics, lithium and loop diuretics or ACE inhibitors, phenytoin and sulfamethoxazole/trimethoprim, sulfonylureas and antimicrobial agents, theophylline and ciprofloxacin, and warfarin and antimicrobial agents or nonsteroidal anti-inflammatory drugs. One study reported the risk for breast cancer-related death as a function of paroxetine exposure among women treated with tamoxifen. Conclusions Several population-based studies have reported significant harm associated drug interactions in elderly patients. Increased awareness and interventions aimed at reducing exposure and minimizing the risks associated with potentially harmful drug combinations are needed.