Bioavailability of Lead to Juvenile Swine Dosed with Soil from the Smuggler Mountain NPL Site of Aspen, Colorado

Bioavailability of lead (Pb) has become an issue in quantifyingexposure of sensitive populations and, where necessary, establishingcleanup levels for contaminated soil. Immature swine were usedas a model for young children to estimate the degree to whichPb from two fully characterized composite samples from the SmugglerMountain Superfund Site in Aspen, Colorado may be bioavailableto resident children. The composite soils contained 14,200 and3870 µg Pb/g of soil. Relative and absolute enteric bioavailabilitiesof Pb in soil (oral dose groups of 75,225, and 675 µgPb/kg body wt/day) were estimated by comparison with an orallyadministered soluble Pb salt (lead acetate = PbAc₂·3H₂O)(dose groups of 0, 75, and 225 µg Pb/kg body wt/day) andan intravenously administered aqueous solution of Pb (100 µgPb/kg/day) from the same trihydrate salt administered dailyfor 15 days to 50 juvenile swine. The biological responses (areaunder the blood Pb concentration-time curve, and the terminalliver-, kidney-, and bone-lead concentrations) produced by Pbfrom PbAc₂·3H₂O and lead-contaminated soils were determined.This study revealed Pb from soil containing 14,200 µgPb/g of soil had a bioavailability relative to Pb from PbAc(RBA), ranging from 56% based on the area under the blood leadconcentration-time curve (AUC) versus dose, to 86% based oncalculations from liver- Pb loading versus dose. Similarly,Pb from soil containing 3870 µg Pb/g of soil had an RBAranging from 58% based on the AUC versus dose, to 74% basedon calculations from liver- and kidney- Pb loading versus dose.Bioavailability of Pb in soils may be more or less than EPA'sdefault RBA of 60%, therefore, measuring site- specific RBAsprovides a basis for improved exposure and risk assessment.     

Effect of Equilibration Zones on Stability, Uniformity, and Homogeneity Profiles of Vapors and Aerosols in the ADG Nose-Only Inhalation Exposure System

Effect of Equilibration Zones on Stability, Uniformity, andHomogeneity Profiles of Vapors and Aerosols in the ADG Nose-OnlyInhalation Exposure System. GREEN, J. D., HELKE, W. F., SCOTT,J. B., YAU, E. T., TRAINA, V. M., AND DIENER, R. M. (1984).Fundam. Appl. Toxicoi. 4, 768–777. A commercially available,inexpensive, nose-only exposure chamber was modified to includeremovable equilibration zones, and the effect of these zoneson chamber performance was determined. Since limited performancedata were available concerning this unit, a more extensive characterizationwas performed. EPA limit concentrations (5 mg/liter) of toluenevapor or corn oil aerosol, and relatively low concentrationsof uranine aerosol (50 pg/liter) were produced by standard techniques.The presence or absence of equilibration zones did not affectthe stability or uniformity of toluene vapor atmospheres, withthe coefficient of variation (CV) not exceeding 3.33% in allexperiments. In contrast, the presence of two equilibrationzones was found to progressively enhance the uniformity of theinhalable test aerosols in the animal exposure zone (CV 3.16%).Matrix sampling revealed that in both uranine and corn oil experiments,the center matrix point concentration was consistently lowerthan samples taken in the actual animal breathing zone. Equilibrationzones markedly reduced the difference between breathing zoneand center point concentrations. These performance data indicatedthat the modified ADG nose-only exposure system performed exceptionallywell with the materials that were studied. Results were comparableto those describing whole-body chamber performance. The readyavailability of this inexpensive prototype lends itself to standardizationof techniques between laboratories     

Acetylcholinesterase Fiber-Optic Biosensor for Detection of Anticholinesterases

Acetylcholinesterase Fiber-Optic Biosensor for Detection ofAnticholinesterases. Rogers, K. R., Cao, C. J., Valdes, J. J.,Eldefrawi, A. T., and Eldefrawi, M. E. (1991). Fundam. ApplToxicol 16, 810–820. An optical sensor for anticholinesterases(AntiChEs) was constructed by immobilizing fluorescein isothiocyanate(FITC)-tagged eel electric organ acetylcholinesterase (AChE)on quartz fibers and monitoring enzyme activity. The pH-dependentfluorescent signal generated by FITC-AChE, present in the evanescentzone on the fiber surface, was quenched by the protons producedduring acetylcholine (ACh) hydrolysis. Analysis of the fluorescenceresponse showed Michaelis–Menten kinetics with a K_appvalue of 420 µm for ACh hydrolysis. The reversible inhibitoredrophonium (0.1 mm) inhibited AChE and consequently reducedfluorescence quenching. The biosensor response immediately recoveredupon its removal. The carbamate neostigmine (0.1 mm) also inhibitedthe biosensor response but recovery was much slower. In thepresence of ACh, the organophosphate (OP) diisopropylfluorophosphate(DFP) at 0.1 mm did not interfere with the ACh-dependent fluorescentsignal quenching, but preexposure of the biosensor to DFP inabsence of ACh inhibited totally and irreversibly the biosensorresponse. However, the DFP-treated AChE biosensor recoveredfully after a 10-min perfusion with pralidoxime (2-PAM). Echothiophate,a quaternary ammonium OP, inhibited the ACh-induced fluorescencequenching in the presence of ACh and the phosphorylated biosensorwas reactivated with 2-PAM. These effects reflected the mechanismof action of the inhibitors with AChE and the inhibition constantsobtained were comparable to those from colorimetric methods.The biosensor detected concentrations of the carbamate insecticidesbendiocarb and methomyl and the OPs echothiophate and paraoxonin the nanomolar to micromolar range. Malathion, parathion,and dicrotophos were not detected even at millimolar concentrations;however, longer exposure or prior modification of these compounds(i.e., to malaoxon, paraoxon) may increase the biosensor detectionlimits. This AChE biosensor is fast, sensitive, reusable, andrelatively easy to operate. Since the instrument is portableand can be self-contained, it shows potential adaptability tofield use.     

Electrical Safety During Electrophysiological Testing

This report describes the inadvertent induction of non-sustained atrial and ventricular arrhythmias due to the malfunction of a programmable cardiac stimulator. The malfunction occurred when line power resumed after a brief municipal power outage ("blackout") during an invasive electrophysiological study. The stimulator spontaneously delivered very high frequency pulses through the electrode catheter to the myocardium which resulted in atrial and ventricular arrhythmias. During bench testing, the stimulator delivered a continuous train of high frequency output pulses (greater than or equal to 1 mA) when line voltage resumed normal level after it had dropped below 65 VAC. Electrical safety during electrophysiological testing requires a stimulator design which is immune to altered operating conditions, and which shuts down if abnormal operating or output conditions are detected.     

POLYTETRAFLUOROETHYLENE (PTFE) GRAFTS FOR HAEMODIALYSIS: PATENCY AND COMPLICATIONS COMPARED WITH THOSE OF SAPHENOUS VEIN GRAFTS

A comparison has been made between polytetrafluoroethylene (PTFE) and saphenous vein as graft material for the construction of arteriovenous fistulas for use in haemodialysis. Fifty patients with PTFE grafts have been examined and compared with 70 patients with saphenous vein grafts. At eighteen months the accumulative patency rate was 69.8% for PTFE grafts and 68.9% for saphenous grafts. Although the PTFE grafts were similar in terms of patency, their complication rate was higher. The infection rate and distal ischaemia rate for PTFE grafts were double those of the vein grafts. Two patients developed median and ulnar nerve paralysis respectively shortly after implantation of PTFE grafts. Because of this it is recommended that their use be restricted to the lower limb. Despite a higher incidence of complications, PTFE grafts are a satisfactory substitute if a suitable saphenous vein is not available.     

Sensitivity and Specificity of the Tilt Table Test in Young Patients with Unexplained Syncope

The usefulness of the head-up tilt testing (HUT) has heen previously addressed in diagnosing vasovagal neuroregulatory syncope in the teenage population. However, data concerning sensitivity and specificity is deficient due to the lack of control groups. We compared the response to HUT in young patients referred because of syncope or near syncope (n = 44, mean age 16 ± 3 years SD) to healthy young volunteers with a normal physical examination and no previous history of syncope (n = 18, mean age 16 ± 2 years) and io determine the sensitivity and specificity of HUT. The graded tilt protocol was performed at 15°, 30°, and 45° (each for 2 min), and then 60° for 20 minutes. Cuff blood pressure was measured every minute and lead IIECG was continuously monitored. Results; 25 of the 44 patients (57%) developed a vasovagaJ response or became symptomatic after 13.8 ± 5.7 minutes of HUT. Three of the 18 volunteers (17%) had a vasovagal response and became symptomatic after 9 ± 3 minutes of HUT. There was no statistical difference among the four groups (with and without tilt induced vasovagal response) in terms of age and baseline hemodynamic data. The sensitivity of 20 minutes HUT was 57% and its specificity was 83%. The presyncopal hemodynamic response in patients with history of syncope that was characterized by a significant decrease in systolic blood pressure and lack of increase of diastolic blood pressure as compared with baseline and with other groups. Gonclusions: 20 minutes at 60° HUT has a high specificity for the diagnosis of vasovagal syncope. Its limited sensitivity is counterbalanced by the advantage of limiting the incidence of false-positive results in patients without the vasovagal syndrome.     

Role of acetylation and charge in antimicrobial peptides based on human β‐defensin‐3

Cationic antimicrobial peptides are an evolutionarily ancient and essential element of innate immunity in higher organisms. The precise mechanism by which these peptides exert their antimicrobial activity on bacteria is not well understood. Decapeptides based on the C‐terminus of human β‐defensin‐3 were designed and evaluated to study the role of charge in defining the antimicrobial activity and selectivity of these peptides against Escherichia coli. Acetylated derivatives of these peptides were prepared in order to further evaluate how positively charged primary amines contribute to potency in these small antimicrobial peptides. These peptides enabled us to explore the relationship between net charge, charge distribution and antimicrobial activity. While the results indicate that net charge is a major factor in antimicrobial activity in these peptides, the actual relationship between charge and potency appears to be more complex.