ABSTRACT
1. The O-dealkylation of 7-alkoxycoumarins is widely used as an assay to characterize cytochrome P450 (CYP) activity. These substrates can also undergo oxidative attack at additional sites on the coumarin nucleus, which may influence their apparent selectivity for particular CYP forms. 2. Accordingly, the effect of blockade of these additional sites was investigated on the selectivity towards rat hepatic CYP forms, with emphasis on the CYP1A and 2B forms. 3. Blockade of the 3-/4- and 6-positions resulted in substrates for which the CYP1A1/2 selectivity of the unsubstituted 7-alkoxycoumarins was altered to a CYP2B selectivity; this was achieved with little overall change in the molecular dimensions of the substrate. Limited analysis of other inducible CYP forms indicated at most only small effects of structure modification on activity. 4. The findings suggest that the sensitivity of probe substrates for CYP forms may be limited by the occurrence of competing side reactions of the substrate, and that better probes may be derived by blocking the sites of these side reactions.
Subject(s)
Coumarins/metabolism , Cytochrome P-450 Enzyme System/metabolism , Microsomes, Liver/enzymology , 7-Alkoxycoumarin O-Dealkylase/metabolism , Adolescent , Adult , Aged , Animals , Coumarins/chemistry , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP2B1/antagonists & inhibitors , Cytochrome P-450 CYP2B1/metabolism , Enzyme Induction/drug effects , Enzyme Inhibitors/pharmacology , Female , Humans , In Vitro Techniques , Isoenzymes/metabolism , Male , Microsomes, Liver/drug effects , Middle Aged , Molecular Probes , Molecular Structure , Phenobarbital/pharmacology , Rats , Rats, Wistar , Selegiline/pharmacology , Substrate Specificity , beta-Naphthoflavone/pharmacologyABSTRACT
An affective, somatic, and memory check-list of symptoms was administered to subjects who had no personal experience or knowledge of head injury. Subjects indicated their current experiences of symptoms, then imagined having sustained a mild head injury in a motor vehicle accident, and endorsed symptoms they expected to experience six months after the injury. The checklist of symptoms was also administered to a group of patients with head injuries for comparison. Imaginary concussion reliably showed expectations in controls of a coherent cluster of symptoms virtually identical to the postconcussion syndrome reported by patients with head trauma. Patients consistently underestimated the premorbid prevalence of these symptoms compared with the base rate in controls. Symptom expectations appear to share as much variance with postconcussion syndrome as head injury itself. An aetiological role is suggested.
Subject(s)
Brain Concussion/psychology , Head Injuries, Closed/psychology , Set, Psychology , Sick Role , Somatoform Disorders/psychology , Activities of Daily Living/psychology , Adult , Brain Concussion/diagnosis , Diagnosis, Differential , Female , Head Injuries, Closed/diagnosis , Humans , Male , Mental Recall , Neuropsychological Tests , Somatoform Disorders/diagnosisSubject(s)
Anxiety/therapy , Biofeedback, Psychology , Skin Temperature , Fingers/blood supply , Humans , Personality InventoryABSTRACT
Compared male and female clients of an emergency care unit for the treatment of alcohol-related crises on a number of basic characteristics and procedural variables. Female clients were found to be significantly younger and more likely to be employed than males. The two groups did not differ reliably with respect to educational level or marital status. Females were found to be referred to the center by Alcoholics Anonymous and family members more often than were male clients, and male clients were referred more often by police than were female clients. The two groups also differed with respect to disposition at time of discharge, with more females judged as not needing additional treatment and more males viewed as needing additional treatment, but family or patient was not ready at the time.
