Self-administration Excessive drinking of ethanol in animals can be produced by a number of factors including altering palatability, genetics, and history of consumption. There is evidence that certain symptoms of withdrawal can persist for a number of weeks or even months following chronic ethanol exposure in humans (Kissin 1979;Begleiter and Porjesz 1979;Alling et al. 1982;Roelofs 1985;Grant et al. 1987) as well as in animals (Begleiter and Porjesz 1979). In human alcoholics, one of the factors leading to excessive drinking is the use of alcohol to relieve or avoid withdrawal symptoms (U.S. Department of Health and Human Services 1990). Fatigue and tension persisted for approximately five weeks following withdrawal in a group of 68 chronic alcoholics (Alling et al. 1982), and periods of hyperventilatory symptomology and anxiety (as determined by the Spielberger State-Trait Anxiety Inventory, a self-report inventory), which correlated with intensity of alcohol craving, were reported for up to nine months following withdrawal in a group of 37 chronic alcoholics (Roelofs 1985).In a larger cohort of 312 abstinent alcoholics, 20-25% of them showed signs of anxiety and depression, as determined from the Symptom Check-List 90 (self-report inventory with coverage of areas of symptomology and psychopathology) six months to two years following withdrawal (De Soto et al. 1985). In a follow-up study, it was shown that distress-related symptoms correlated with relapse in alcoholics who were abstinent for less than two years (De Soto et al. 1989). The more pro- Received March 2, 1999; revised August 25, 1999; accepted December 6, 1999. 582 A.J. Roberts et al. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 6 tracted symptoms tended to be subacute, were often affective in nature, and appeared to precede relapses into uncontrolled alcohol drinking. For example, depression and anxiety associated with withdrawal were found to provoke drinking in 83 of 100 male alcoholics who experienced these symptoms (Hershon 1977). These patients reported that they drank alcoholic beverages when they experienced anxiety and depressed mood. In another study, both male and female alcoholics reported negative emotions as the most common trigger of relapse (Annis et al. 1998). The clinical literature suggests that alterations in affective state persist for quite some time following alcohol withdrawal and may actually be partly responsible for some relapse episodes in alcoholics.Potential rodent models of excessive ethanol drinking include the alcohol deprivation effect in nondependent animals, ethanol self-administration in dependent withdrawing animals, and ethanol self-administration in animals with a history of dependence following periods of abstinence. The alcohol deprivation effect is a transient increase in ethanol self-administration in animals following periods of abstinence from ethanol for several days to several weeks (Sinclair and Senter 1967;Spanagel et al. 1996;Heyser et al. 1997;Hölter et al. 1998). This increase in e...
Objectives-To determine the kinetics of elimination of urinary dialkylphosphate metabolites after oral and dermally applied doses of the organophosphate pesticide chlorpyrifos to human volunteers and to determine whether these doses aVected plasma and erythrocyte cholinesterase activity. Method-Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood samples were taken over 24 hours and total void volumes of urine were collected over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos was administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyrifos was washed from the skin and retained for subsequent measurement. The same blood and urine sampling regime was followed as for the oral administration. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlorpyrifos-diethylphosphate and diethylthiophosphate-was determined for each urine sample. Results-The apparent elimination half life of urinary dialkylphosphates after the oral dose was 15.5 hours and after the dermal dose it was 30 hours. Most of the oral dose (mean (range) 93% (55-115%)) and 1% of the applied dermal dose was recovered as urinary metabolites. About half (53%) of the dermal dose was recovered from the skin surface. The absorption rate through the skin, as measured by urinary metabolites was 456 ng/cm 2 /h. Blood plasma and erythrocyte cholinesterase activity did not fall significantly during either dosing regime. Conclusion-An oral dose of chlorpyrifos was readily absorbed through the skin and almost all of the dose was recovered as urinary dialkylphosphate metabolites. Excretion was delayed compared with the oral dose. Only a small proportion of the applied dose was recovered during the course of the experiment. The best time to collect urine samples for biological monitoring after dermal exposure is before the shift the next day. The amounts of chlorpyrifos used did not depress acetyl cholinesterase activity but could be readily detected as urinary dialkylphosphate metabolites indicating that the urinary assay is a more sensitive indicator of exposure. (Occup Environ Med 1999;56:10-13) Keywords: biological monitoring; chlorpyrifos; organophosphorus pesticideThe organophosphate pesticide chlorpyrifos (O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl) phosphothioate) is a non-systemic cholinesterase inhibitor used to combat agricultural and horticultural insect pests. Several pesticide formulations containing chlorpyrifos have been marketed by diVerent manufacturers. These include Dursban, Lorsban, Brodan, Eradex, and Spannit. A study of the metabolism of chlorpyrifos in rats has shown that the major metabolites are diethylphosphate, diethylthiophosphate, and 3,5,6-trichloro-2-pyridinol.
The role of pyroglyphid mites in house dust allergy is well established and the major allergens from the common house dust mites (Dermatophagoides species) have been characterized. There is, however, relatively little progress in the understanding of the human IgE response to non-pyroglyphid storage mites, allergenic crossreactivity with other mite species and extent of environmental exposure. We studied 196 individuals from an urban environment who were not occupationally exposed to storage mites and found a 24% prevalence of specific IgE antibody to Dermatophagoides pteronyssinus and a 14% prevalence of RAST positivity to at least one of three storage mites, Acarus siro, Lepidoglyphus destructor and Tyrophagus longior. All individuals with a positive RAST to storage mites had specific IgE to D. pteronyssinus. RAST inhibition studies with the eight sera with greater than 2% RAST binding to both families of mites showed considerable crossreactivity between D. pteronyssinus and the storage mites A. siro and T. longior and limited crossreactivity between D. pteronyssinus and L. destructor. This suggests that at least some of the response to storage mites observed by direct RAST is a consequence of crossreactivity with the more abundant D. pteronyssinus.
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