Total mercury levels in selected human tissues, Idaho-1973-74(1,2)

Total mercury levels were determined in human tissues taken at autopsy from six hospitals in the three basic geographical areas of Idaho. Of the 242 specimens analyzed, 76 percent contained detectable mercury. Levels were compared with respect to the age, sex, and geographic residence of autopsied individuals. Mean levels detected were 1.04 ppm in kidney tissue, 0.34 ppm in liver, and 0.08 ppm in brain. Mean mercury levels for the three geographical areas were: southeastern Idaho, 0.22 ppm; southwestern Idaho, 0.80 ppm; and northern Idaho, 0.43 ppm. The relatively high means in southwestern Idaho specimens may be related to the preponderance of natural cinnabar deposits in that portion of the State. Mercury levels were higher in women than men for all tissues in both the southwestern and northern areas, but the reverse was true in the southeast. Data were compared with findings of other investigators in an attempt to arrive at background levels of total mercury residues in human tissues.     

Proton magnetic resonance spectroscopic determination of disulfiram: collaborative study

A proton magnetic resonance spectroscopic method for determining disulfiram in the bulk drug product and in the formulated material was collaboratively studied. The method depends on the use of chloroform-d as a solvent and hexamethylcyclotrisiloxane as the internal standard. No interference from tablet excipients was observed. The method is rapid and specific. Eighteen laboratories analyzed duplicate samples of a bulk drug product, a 250 mg tablet composite, and a 500 mg tablet composite. The average per cent results and standard deviations were 99.7 +/- 1.4, 100.9 +/- 2.0, and 99.9 +/- 2.2, respectively.     

Intravenous anesthesia

Anticholinergics, tranquilizers, and sedative-hypnotics are the usual agents used for preanesthetic sedation of the horse. Of these drugs, the anticholinergics are of little importance in the horse. Acepromazine is the most useful and widely used tranquilizer, whereas xylazine is a safe and popular sedative. A newer sedative recently made available to the veterinarian for clinical use in horses is detomidine. Thiobarbiturates are seldom used alone any longer but are still useful when combined with guaifenesin for induction and maintenance of anesthesia. Other, more contemporary drug combinations that have largely replaced thiobarbiturates and chloral hydrate include xylazine with ketamine, xylazine with Telazol, detomidine with Telazol, and guaifenesin with ketamine and xylazine.     

The role of food consumption factors in establishing drug tolerances

The Center for Veterinary Medicine's food consumption policy was adopted in 1978 before suitable data were available on the consumption of organ meats. Consumption is expressed in terms of amounts expected to be consumed daily by an adult human. Before the Center for Veterinary Medicine (Center) can choose a suitable database to develop a new guideline, the Center must resolve a number of difficult policy choices. After the policy issues are resolved, the Center could use the 1977-78 USDA National Food Consumption survey or an approach based on carcass yield to develop the new guideline.     

Anesthetic potency of nitrous oxide in young swine (Sus scrofa)

Determination of nitrous oxide (N2O) potency was accomplished by extrapolation using the concepts of minimum alveolar concentration (MAC) and additivity among inhalation anesthetics. Halothane and isoflurane anesthetic requirement (alveolar concentration) necessary to achieve MAC in 9 pigs decreased with each successive increase in the percentage of inspired N2O (25%, 50%, 75%). Halothane and isoflurane MAC was determined to be 0.94 +/- 0.03 and 1.75 +/- 0.01 volumes percent, respectively. Halothane and isoflurane requirements decreased to 0.74 +/- 0.02, 0.66 +/- 0.02, and 0.58 +/- 0.02; and to 1.56 +/- 0.02, 1.38 +/- 0.02, and 1.08 +/- 0.03 volumes percent with 25%, 50%, and 75% N2O, respectively. The line of best fit derived from regression analysis of the combined data (isoflurane and halothane MAC values) had a correlation coefficient of 0.987 and an X intercept equivalent to 195% N2O. The potency of N2O in pigs was similar to that of other domesticated mammals and reduced halothane and isoflurane anesthetic requirements by approximately 50% of the reduction observed in human beings.     

Design of bioelectronic interfaces by exploiting hinge-bending motions in proteins

We report a flexible strategy for transducing ligand-binding events into electrochemical responses for a wide variety of proteins. The method exploits ligand-mediated hinge-bending motions, intrinsic to the bacterial periplasmic binding protein superfamily, to establish allosterically controlled interactions between electrode surfaces and redox-active, Ru(II)-labeled proteins. This approach allows the development of protein-based bioelectronic interfaces that respond to a diverse set of analytes. Families of these interfaces can be generated either by exploiting natural binding diversity within the superfamily or by reengineering the specificity of individual proteins. These proteins may have numerous medical, environmental, and defense applications.     

Molecular and neuronal substrate for the selective attenuation of anxiety

Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the alpha2 or alpha3 GABAA (gamma-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the alpha2(H101R) point mutation but present in mice with the alpha3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha2 GABAA receptors, which are largely expressed in the limbic system, but not by alpha3 GABAA receptors, which predominate in the reticular activating system.