Agricultural diseases on the move early in the third millennium.

With few exceptions, the diseases that present the greatest risk to food animal production have been largely similar throughout the modern era of veterinary medicine. The current trend regarding the ever-increasing globalization of the trade of animals and animal products ensures that agricultural diseases will continue to follow legal and illegal trade patterns with increasing rapidity. Global climate changes have already had profound effects on the distribution of animal diseases, and it is an inevitable reality that continually evolving climatic parameters will further transform the ecology of numerous pathogens. In recent years, many agricultural diseases have given cause for concern regarding changes in distribution or severity. Foot-and-mouth disease, avian influenza, and African swine fever continue to cause serious problems. The expected announcement of the global eradication of rinderpest is one of the greatest successes of veterinary preventative medicine, yet the closely related disease peste des petits ruminants still spreads throughout the Middle East and Asia. The spread of novel strains of bluetongue virus across Europe is an ominous indicator that climate change is sure to influence trends in movement of agricultural diseases. Overall, veterinary practitioners and investigators are advised to not only maintain vigilance against the staple disease threats but to always be sufficiently broad-minded to expect the unexpected.

Assessment of the risk of introducing foot-and-mouth disease into Panama via a ferry operating between Cartagena, Colombia and Colon, Panama.

It should be emphasized that the proposed ferry hazard categorizations do not represent absolute risks for introducing FMD into Panama, but instead provide a systematic method for comparing and estimating risks in the absence of quantitative data. A hazard rating of high may not necessarily represent a high quantitative risk for the introduction of FMD, but is high when compared to other scenarios. A low hazard rating may estimate a low quantitative risk of importing FMD, but economic consequences of a potential outbreak should also be considered. When further data become available, a more complete assessment of the risks of the Crucero Express compared to airplanes, cargo boats, and small boats can be performed. At present, the risk of the Crucero Express is at least as low as the other transport modes described above. Since vehicles are not presently allowed transport from Colombia to Panama, they present no risk to Panama, but with proper cleaning and disinfection procedures, vehicles can be permitted with low risk. However, the Crucero Express can carry 125 vehicles, and thorough cleaning and disinfection of this many cars will require modern and efficient facilities not yet present at either port.

Antagonism of marihuana effects by indomethacin in humans.

To investigate whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin antagonized the effects of marihuana, an exploratory single-blind, placebo-controlled study was conducted. Subjects (n = 4) smoked marihuana after pre-treatment with placebo and indomethacin. The subjective rating of marihuana "high", heart rate, word recall, time estimation/production, and plasma concentrations of THC and PGE2 were measured. It was found that: 1) indomethacin pre-treatment decreased the elevation of prostaglandins induced by THC; 2) indomethacin significantly attenuated the subjective "high" and the heart rate accelerating effects of THC, although the magnitude of this effect was modest; 3) indomethacin abolished the profound effect of THC on time estimation and production; and 4) indomethacin pretreatment did not affect the decremental effects of THC on word recall. We conclude that prostaglandins are involved in the neurophysiologic mechanisms that mediate some of the typical clinical effects of THC, particularly the distortion of time perception.

Clinical effects of methamphetamine vapor inhalation.

Despite the increasing popularity of crystalline methamphetamine ("ice") vapor inhalation, no investigations have reported drug plasma concentrations and effects. Under controlled laboratory conditions, six subjects were studied. Plasma concentrations of methamphetamine were determined, and subjective and cardiovascular effects were measured. Methamphetamine appeared in plasma rapidly, increased slowly over the next four hours and then progressively declined. The dose of methamphetamine administered produced modest ratings of subjective drug effects, and moderate changes in cardiovascular parameters. Both subjective and cardiovascular effects rapidly decreased despite the presence of sustained concentrations of methamphetamine in plasma.

Clinical effects of daily methamphetamine administration.

This study investigated alterations in the disposition and pharmacodynamics of methamphetamine HCl after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCl as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2-14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of "high," and plasma concentrations of methamphetamine were examined on days 1 and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 [F(1,5) = 8.26, p less than or equal to 0.035]. However, no significant change in either the subjective ratings of "high" or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed.

The pharmacologic effects of daily marijuana smoking in humans.

Six healthy male, paid volunteers smoked one NIDA cigarette containing 1.0% THC each day for 13 consecutive days. They were tested before and after the period of drug administration by the following procedure: the subjects smoked one NIDA marijuana cigarette containing 1.0% THC followed 15 minutes later by the intravenous infusion of 52 micrograms/min of deuterated THC for 50 minutes. The THC plasma concentrations, ratings of "high" and heart rate effects produced by the combined drug administration were measured, and absolute bioavailability of smoked THC was calculated on Days 1 and 22. Statistical analyses indicate that the only significant changes induced by daily marijuana exposure were in cardioacceleration.

Phospholipid is required for the processing of presecretory proteins by detergent-solubilized canine pancreatic signal peptidase.

The ability of canine pancreatic signal peptidase to remove the signal peptide portion of presecretory proteins in a translocation-independent assay is shown to require phospholipid. Sodium deoxycholate extracts of canine pancreatic rough microsomes containing both signal peptidase and phospholipid were delipidated by gel filtration chromatography on Sepharose CL-6B equilibrated with 0.2% deoxycholate. Column fractions were assayed for signal peptidase activity both with and without the addition of ethanol-extracted soybean phospholipid at a final concentration of 1.0 mg/ml. A peak of signal peptidase activity was detected only when the fractions were assayed with added phospholipid. Phospholipid assays demonstrated that the peak of signal peptidase activity was cleanly separated from phospholipid. The ratio of protein to phospholipid in the deoxycholate extract of rough microsomes was 1.76 while that of the most active signal peptidase fractions ranged from 46.1 to 138. The peak of signal peptidase activity exhibited an apparent Stokes radius of 55 A. Highly purified preparations of phosphatidylcholine were most effective in restoring activity to delipidated signal peptidase. Phosphatidylinositol was much less effective. Phosphatidylserine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine were all ineffective.

Second-harmonic generation in planar waveguides of doped silica.

Second-harmonic generation was produced in germanium-doped silica planar waveguides prepared by simulfaneous illumination with 1064- and 532-nm laser light. During preparation using prism coupling to specific waveguiding modes, the film-generated second-harmonic intensity grew as a function of preparation time until it saturated. The growth rate and saturation level for p-polarized second-harmonic intensity was an order of magnitude greater than that observed for the s polarization. The efficiency for a 2-cm waveguide length was at least 0.5%. The comparison of experimental results indicates a mechanism for this planar geometry that is similar to that producing harmonic effects in optical fibers.

Interaction between ethanol and calcium channel blockers in humans.

The purpose of this study was to test the hypothesis that pretreatment with Ca2+ channel blockers would antagonize the effects of ethanol intoxication in humans. The Ca2+ channel blockers verapamil and nifedipine were chosen because preclinical research has shown them to decrease certain behavioral effects of ethanol in animals. Sixteen healthy, male, paid volunteers, moderate users of ethanol, participated in the study (six in the verapamil and 10 in the nifedipine paradigms). Gelatin capsules containing verapamil (80 mg, 160 mg, or placebo) were administered orally 90 min before ethanol ingestion; whereas, gelatin capsules containing nifedipine (10 mg, 20 mg, or placebo) were administered 30 min before ethanol ingestion. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Subjects were tested in a single-blind, latin-square, cross-over design with each of the following six conditions: placebo ethanol-placebo blocker, placebo ethanol-low dose blocker, placebo ethanol-high dose blocker, ethanol-placebo blocker, ethanol-low dose blocker, and ethanol-high dose blocker. The variables measured in this study were subjective rating of ethanol intoxication, Addiction Research Center Inventory alcohol scale, heart rate, blood pressure, short-term memory, accuracy and latency of response in the Simulator Evaluation of Drug Impairment task, and blood ethanol concentrations by breath analyzer. Results indicate that pretreatment with either verapamil or nifedipine failed to antagonize the inebriating effects of ethanol including its decremental effects on short-term memory and psychomotor performance.

Expression of functional human acid beta-glucosidase in COS-1 and Spodoptera frugiperda cells.

A cDNA encoding human acid beta-glucosidase (N-acylsphingosyl-1-O-beta-D-glucoside: glucohydrolase, EC 3.2.1.45) expressed catalytically active enzyme in transfected COS-1 or infected Spodoptera frugiperda (Sf9) cells. The expression plasmid p91023(B) (p91023B/Glc) and a Baculovirus (AcMNPV/Glc) containing the cDNA were constructed and used with the respective cells. By immunoblotting a glycosylated, 63-kilodalton human acid-beta-glucosidase was detected in the transfected or infected cells. A 56-kilodalton human polypeptide was obtained after complete deglycosylation with N-Glycanase. The expressed human enzymes also had partial endoglycosidase H sensitivity. The human enzyme expressed at high levels in Sf9 cells and had normal immunologic properties. With the partially purified enzyme from Sf9 cells, intact function of active site was indicated by normal kcat and Kmapp or Kiapp values for alternative substrates or potent inhibitors, respectively. The expressed enzyme was also activated normally by the negatively charged lipid, taurocholate. The results of these studies indicate that the Baculovirus expression system could provide a convenient source of normal human enzyme for structure/function investigations. In addition, this expression system should prove useful for the identification and evaluation of putative etiologic point mutations in Gaucher disease variants with kinetically altered residual enzymes.

Clostridium botulinum type C in the Mersey estuary.

Nineteen of 98 samples of mud or sand taken from the Mersey estuary in 1981 contained Clostridium botulinum type C, the organism almost always responsible for botulism in water birds. In the Dungeon and Score Bank areas, where many dead and dying birds were found during the period September-December 1979, almost half the samples contained type C. Most of the positive samples were essentially muddy rather than sandy. The findings do not prove that botulism contributed to the 1979 mortality but are nonetheless thought-provoking, particularly because type C--unlike type B--is by no means ubiquitous in Britain. Type B was present in 12.2% of samples from the Mersey estuary.

Interaction between ethanol and dextroamphetamine: effects on psychomotor performance.

The objective of this study was to investigate the interaction between ethanol and dextroamphetamine with regard to psychomotor performance. Twelve healthy, male, paid volunteers, moderate users of ethanol and amphetamines, participated in this study. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Five minutes before the termination of ethanol or placebo ingestion, dextroamphetamine elixir (0.09 mg/kg, 0.18 mg/kg or placebo) diluted in 50 ml of orange juice was administered. Subjects were tested in a single-blind, latin-square, crossover design with each of the following six conditions: placebo ethanol/placebo dextroamphetamine; placebo ethanol/low-dose dextroamphetamine; placebo ethanol/high-dose dextroamphetamine; ethanol/placebo dextroamphetamine; ethanol/low-dose dextroamphetamine; and ethanol/high-dose dextroamphetamine. The variables measured in this study were: subjective rating of ethanol and dextroamphetamine intoxication, accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI task), blood ethanol concentration by breath analyzer, and plasma concentrations of dextroamphetamine by gas chromatography. Results indicate ethanol induced decrements in performance of the skills necessary to drive an automobile were significantly decreased by dextroamphetamine in a dose-response fashion. The administration of dextroamphetamine did not decrease the subjective ratings of ethanol intoxication.

Linear optical effects in z-scan measurements of thin films.

We show that it is possible, in Z-scan measurements ofthin films, to obtain data that closely resemble typical results for nonlinear optical materials, but which actually arise from linear optical effects caused by sample damage. Z-scan measurements on a silica-based thin film yielded the expected peak-valley signature of Z-scan data, but subsequent analysis and microscopic examination of the film indicated that the data resulted from an ablation hole produced in the film when it was near the laser focus. The resulting spatial variation of the linear refractive index of the film produced a lensing effect that mimicked the typical Z-scan response. Scalar diffraction theory was used to model the effects of a spatially varying refractive index and gave results that qualitatively agreed with the Z-scanmeasurements.

Planar geometry thin-film all-optical programmable switch.

We describe an all-optical programmable switch that can perform logic gate functions. This switch consists of a planar geometry germanium-doped silica waveguide, a Q-switched and mode-locked Nd:YAG laser, and the means of coupling laser light into different waveguiding modes of the thin film at the fundamental and second-harmonic frequencies. By the application of the appropriate optical programming sequence, the film-generated second-harmonic light can be made to perform the functionalities of various gates. In particular, a single waveguide was optically programmed to perform the Or function and was then made to perform the And function with little change to the experimental arrangement.

Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride.

S-(+)-methamphetamine hydrochloride ("ice") is abused by smoking (inhaling the vapors of the material). Male human volunteers inhaled the drug from a pipe heated at 300 degrees-305 degrees C for an average inhaled dose of 21.8 +/- 0.3 (SE) mg. The same volunteers were given an intravenous injection of 15.5 mg of S-(+)-methamphetamine hydrochloride. Methamphetamine and its metabolite amphetamine were analyzed in plasma, saliva, and urine by gas chromatography. The bioavailability of smoked methamphetamine was 90.3 +/- 10.4%. (Oral bioavailability calculated from this study and a previous one was 67.2 +/- 3.1%). The geometric mean plasma half-life was 11.1 hr for smoked methamphetamine and 12.2 hr for the intravenous drug. These values agreed with urinary excretion rate data. The volume of distribution in the elimination phase was 3.24 +/- 0.36 liter/kg for the smoked dose and 3.73 +/- 0.59 liter/kg for the intravenous dose. The mean residence times were 11.5 +/- 0.5 hr and 11.3 +/- 1.74 hr for the two routes. Metabolic clearance represented 58 and 55%, respectively, of the total clearance. Significant amounts of the drug (37-45% of the nominal dose) were excreted in urine as methamphetamine and lesser amounts (7% of the nominal molar dose) as amphetamine. Renal clearance was equivalent for the two routes. Methamphetamine concentrations in plasma after inhalation showed a plateau. A model involving both a fast and a slow input function fit the data from 4 of the 6 subjects and indicated a terminal elimination rate that agreed with results from model-independent pharmacokinetic calculations. The drug caused significant subjective and cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans.

The pharmacokinetics of orally administered S-(+)-methamphetamine-d3 were investigated in human male volunteers before and after a 13-day course of a slow release form of S-methamphetamine hydrochloride. A one-compartment pharmacokinetic model incorporating a lag time fits the data best. The average elimination half-life was 10.1 hr (range of 6.4-15.1 hr). There were no statistically significant differences in pharmacokinetic parameters when a low dose (0.125 mg/kg) was given before and after the 13-day oral regimen. When a higher challenge dose (0.250 mg/kg) was used, the maximum plasma concentration of methamphetamine-d3 was slightly but significantly greater when the test dose was given at the end of the oral dosing period than when it was given at the beginning. Although minor differences in pharmacokinetics occur after subchronic treatment with low doses of methamphetamine, their result would be to increase plasma concentration of the drug. Therefore, development of pharmacodynamic tolerance to methamphetamine could not be explained on the grounds of a change in pharmacokinetics.