Structural and steric requirements for β-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in the rat limbic forebrain

Summary The present studies were undertaken to assess the structural and steric requirements for -phenethylamines as agonists of the noradrenergic cyclic AMP generating system in slices of the rat limbic forebrain. Significant agonist activity of -phenethylamines requires a -3,4-dihydroxyphenethylamine with a -hydroxyl group in the R configuration. Thus, dopamine did not stimulate the system at concentrations up to 10^–3 M. Moreover, -hydroxyphenethylamines without a 3,4-catechol group (octopamine, phenylephrine, p-hydroxynorephedrine, metaraminol and methoxamine)-though exerting -agonist activity in peripheral tissues-lack agonist activity in this particular cyclic AMP generating system. The effects of (R)-norepinephrine and (R)-isoproterenol at maximal concentrations were not additive. The results lend further support to the view that the cyclic AMP generating system in slices of the limbic forebrain is part of a norepinephrine receptor coupled adenylate cyclase system with a subpopulation of receptors that are in nature.     

The effects of a subjective monitoring task in the physiological measure of genital response to erotic stimulation

Instrumentation has been developed which promises to further our understanding of the relationship between cognitive and physiological factors in the sexual arousal process. Past research has examined this relationship by continuous measurement of genital response, and discrete posttest measurement of subjective arousal. The self-report or cognitive lever allows individuals to rate feelings of arousal continuously throughout a stimulus interval by positioning a lever device along a calibrated scale. In this way, structural patterns of physiological and cognitive response can be examined. However, since attention has been shown to be an important cognitive operation in the processing of sexual stimuli, there is concern that this subjective measuring task may confound laboratory assessment by altering genital responsivity through distractive or possibly facilitative mechanisms. In order to test the methodological limitations of the cognitive lever, 14 male and female college students were exposed to duplicate viewings of erotic videotapes while alternately using and not using the self-report device. Results indicated that lever usage was not obtrusive in females, but was in males to the point of altering physiological response. In addition, the study took advantage of the continuous, concurrent measurements and examined patterns of convergence and divergence between the two. Results of correlational analyses indicated, in line with past research, that for men greater degrees of erection result in significantly higher subjective-objective agreement. Patterns for women as a group were much less clear, with only two significant correlations appearing. Finally, the limitations of the cognitive lever were discussed.This research was funded in part by VA Merit Review Research Grant 041-34-7119 and NIMH Grant MH33553.     

Hexachlorophene and the central nervous system

Summary A study on hexachlorophene encephalopathy in mice and baboons is reported. By light microscopy, a severe spongiform lesion of the central nervous system (CNS) was localized in the white matter, without myelin breakdown or cellular reaction. By electron microscopy, the myelin alteration was characterized by wide intralamellar spaces or splitting developed in the intraperiod line of compact sheaths. The acute changes described were induced by administration of the drug by the digestive or cutancous routes at various dosage levels in an aqueous solution or in talcum powder. The toxic effects depended on the age of the animals, the survival times and the concentrations of hexachlorophene, i.e., 6%, 3%, and 0.5%. The findings are compared with previous reports on the neurotoxicity of hexachlorophene and other chemicals in humans and experimental animals. Hexachlorophene cannot be recommended for use in young infants because of its neurotoxicity in very low doses as demonstrated in the present report.     

Difficulty and discrimination capacity of examinations estimated on the basis of repeated student failure

This paper examines the difficulty and discrimination capacity of several subjects for problematic students, i.e., those failing repeatedly (re-examined four or more times) in at least one subject. Four hundred and six problematic students were analysed. The difficulty in passing thirty-one mandatory subjects was assessed in two ways:

• 1 on the basis of the attrition rate of the students due to pass the subject,
• 2 on the basis of the percentage of number of failures over the number of examinations.

The discrimination capacity of the same subjects was assessed on the basis of ‘false positive’ and ‘false negative’ results. The result of the evaluation of one subject was considered a false positive if it gave an excellent mark to a problematic student; it was considered a false negative if a student had to be reexamined four or more times before passing, although he had at least one excellent passing mark in one or more subjects. There were 157 excellent marks given to 114 problematic students. The two ways to assess difficulty ranked the thirty-one subjects in a very significantly-similar way. The subjects of the first, second and sixth years of study were considerably more difficult than the other years. A high proportion of false-negative results in a subject did not imply necessarily increased difficulty and vice versa. Thus, only two of the five subjects with the highest proportion of false-negative results belonged to the group of the five most difficult subjects. Also, three of the five subjects with the highest proportion of false-positive results belonged to the group of the five easiest subjects. Finally, only one of the five subjects with the lowest proportion of false (positive plus negative) results belonged to the group of the five most difficult subjects. Examination systems involving oral examinations either alone or in conjunction with written ones were more difficult for the problematic students than those involving purely written examinations, while their discrimination capacity was not significantly different. The discrimination capacity of the subjects involving practical examinations as part of their evaluation system was significantly better than that of those not involving practical examinations. It is concluded that a very permissive examination system presents the problem of repeatedly-failing students. A quasi-open admission system, as in Athens University, associated with a very permissive examination system, leads to a pattern of difficulty, the peaks of which appear, mainly, in the first and last year of studies.     

Effect of occupational mercury exposure on plasma lysosomal hydrolases

Summary The activities of three plasma lysosomal hydrolases, -galactosidase, -glucuronidase and -N-acetylglucosaminidase, were studied in 20 workers exposed to metallic mercury vapor in a chlorine alkali plant and in 10 nonexposed referents. The urinary excretion and blood levels of mercury were determined on the day of study, and the history of mercury exposure was reviewed from the records of mercury concentrations in urine and blood over periods of up to 133 months. The average levels of -N-acetylglucosaminidase and -glucuronidase were higher in the plasma of exposed workers, but the difference was not significant. No significant positive correlation was seen between lyosomal enzyme activities and cumulative long-term exposure to mercury. It is concluded that measurement of plasma lysosomal hydrolase-activities is not of great value in the biological monitoring of workers exposed to low concentrations of metallic mercury vapor.In line with published data, the concentration of mercury showed a clearcut diurnal variation in nonexposed persons, persons currently exposed and persons with a history of past exposure. The excretion rate of mercury remained constant throughout the day.     

Reduced platelet MAO activity in healthy male students with blood group O

The association between the two genetic markers of affective disorders, ABO blood group system and platelet MAO (monoamine oxidase) activity was studied in 70 healthy young males. The platelet MAO activity of subjects with blood type O was significantly lower than that of subjects with blood type A and with blood types A + B AB + B together. This finding could constitute a "bridge" between the two genetic approaches to affective disorders.     

Interstitial chemotherapy for brain tumors: review

An extensive effort to search for curative chemotherapeutic approaches has found no breakthrough in management of patients with malignant brain tumors. Despite the trials with new agents or protocols of multiple agents, systemic chemotherapy has failed to provide reliable clinical response. Interstitial chemotherapy has been practiced for malignant brain tumors with administering chemotherapeutic compounds directly into the tumor which provide increased and prolonged drug concentration in the tumor, reduction of systemic toxicity and bypassing the blood-brain barrier. These theoretical advantages encourage further pursuing interstitial chemotherapy for patients with malignant brain tumors who would otherwise be always fatal.In this review, the literature has been reviewed to identify methods toxicity and efficacy of interstitial chemotherapy. Clinical and experimental data indicate limited toxicity and promising efficacy. Various methods to administer the agents were utilized; intraoperative topical application, local injections through catheters or implantable controlled drug delivery system. Selection of ideal chemotherapeutic agents and development of drug delivery system need further investigations.     

Structure and measurement of dimensions of risk for HIV transmission in injecting drug users

Dimensions of HIV infection risks were investigated in 1,245 injecting drug users (IDUs) in Sydney, Australia. Factor analysis of the degree of risk of the 33 items of risk behaviours revealed ten dimensions, which covered the domains of oral sex, withdrawal before ejaculation, protected intercourse, unprotected vaginal intercourse, saliva, blood products, manual sex, needles and syringes, unprotected anal sex, and social transmission. The perceived riskiness of particular activities closely approximated the objectively assessed risk of particular practices. Women assessed the risks of classes of activities (with the exception of oral sex) as being higher than did men. IDUs appear to have readily interpretable and consistent perceptions of HIV transmission risks, and these dimensions have utility for measuring perception and knowledge of HIV transmission risks.