[(125)I]3beta-(4-ethyl-3-iodophenyl)nortropane-2beta-carboxylic acid methyl ester ([(125)I]EINT): a potent and selective radioligand for the brain serotonin transporter.

The binding characteristics of [(125)I]3beta-(4-ethyl-3-iodophenyl)nortropane-2beta-carboxylic acid methyl ester ([(125)I]EINT), a high-affinity selective ligand for the serotonin transporter (5-HTT), and its binding characteristics to rat brain membranes were determined. [(125)I]EINT binding to rat cerebral cortex membranes was saturable and reversible, and its specific binding represented approximately 90% of the total binding. [(125)I]EINT labeled a single site with K(d) = 0.22 +/- 0.03 nM and B(max) = 583 +/- 38 fmol/mg protein. Kinetic analysis revealed a t(1/2) for association and dissociation of 20 and 24 min, respectively. Pharmacological characterization of [(125)I]EINT confirmed its high specificity for the 5-HTT. The pattern of brain region distribution in vivo of intravenously administered [(125)I]EINT indicated greater accumulation of the radioligand in 5-HTT-rich brain regions. However, the signal-to-background ratio was low. Thus, [(125)I]EINT appears to be a useful radioligand for studying the 5-HTT in vitro, but it may not be a good in vivo ligand.

Relationship between acrylamide reproductive and neurotoxicity in male rats.

To determine whether there is a relationship between the reproductive and neurotoxic effects of acrylamide monomer (AM), the first week of the study design of Sublet et al. ¿14 was duplicated: Long-Evans male rats were gavaged with AM in water, 25/group, at 0, 5, 15, 30, 45, or 60 mg/kg/day for 5 days (days 1 through 5). On Day 8, males were paired overnight with untreated virgin females (1 : 1) in proestrus/estrus. On day 9, males were evaluated for forelimb and hindlimb grip strength. Five males/group were perfusion fixed, 20/group were used for andrologic assessment, and all were necropsied. Perfusion-fixed sciatic nerves were examined histologically. Sperm-positive females were examined for preimplantation and postimplantation loss at midpregnancy. At 15 to 60 mg/kg/day, males exhibited significantly reduced weight gain, reduced mating, fertility, and pregnancy indices by trend analysis (significant at 60 mg/kg/d by pairwise comparison), and increased postimplantation loss and dominant lethal factor, F(L)%, at 45 and 60 mg/kg/day. At 60 mg/kg/day, the sperm beat cross frequency was increased, with no significant effects on epididymal sperm motility or concentration, and hindlimb grip strength was decreased, with no pathologic lesions in sciatic nerves. Therefore, epididymal sperm, mating, and neurotoxic effects were observed at AM doses that also resulted in increased postimplantation loss, possibly by different mechanisms.

Gestational nicotine exposure alone or in combination with ethanol down-modulates offspring immune function.

Prenatal nicotine exposure has been shown to disrupt the development of a number of peripheral organs. In the current study, we examined the effects of gestational nicotine exposure, alone or in combination with ethanol exposure, on offspring immune function. Timed pregnant rats were treated with either nicotine (6 mg/kg/day) from gestation day 4-20 using subcutaneously implanted osmotic mini-pumps or ethanol administered in the drinking water (15% w/v) from gestation day 10-20. The combined exposure group received both treatments. The ability of offspring T and B cells to proliferate in response to nonspecific stimulation by Concanavalin A or lipopolysaccharide, respectively, was determined on postnatal days 9, 15, 22, 29, 64, and 86. Offspring splenocyte beta(2)-adrenoceptor binding was also measured. Nicotine or nicotine+ethanol suppressed splenocyte responsiveness to Concanavalin A or lipopolysaccharide which was similar in timing and magnitude to that seen with ethanol alone. Splenocytes from these groups remained subresponsive to stimulation well into adulthood. The combined drug treatment caused an overall reduction in spleen beta-adrenergic receptor binding whereas the individual drug treatments did not alter the development of spleen beta-adrenergic receptors.Our results indicate that prenatal nicotine exposure can cause long-term suppression of the proliferative response of offspring immune cells. Moreover, the effects of nicotine+ethanol may cause more severe deficits in adulthood.

Effects of lactational administration of acrylamide on rat dams and offspring.

We duplicated the study design of Husain et al. (Ind Health 1987; 25:19-28) to determine whether maternal exposure to acrylamide monomer (AM) resulted in offspring neurotoxicity. Wistar rat dams with litters (15/group) were gavaged with AM in saline at 0 or 25.0 mg/kg/d throughout lactation (pnd 0-21). Maternal feed and water consumption, body weights (BW), and Functional Observational Battery (FOB) were recorded. At weaning (pnd 21), maternal sciatic nerves were examined histologically. Male offspring were retained until pnd 91, with BW and grip strength evaluations. Dosed dams exhibited progressive toxicity, including mortality (two), severely reduced feed and water consumption, BW, and BW gain, and behavioral neurotoxicity (with no sciatic nerve pathology). Nursing offspring at 25.0 mg/kg/d exhibited increased mortality and reduced BW associated with little/no milk in stomachs. Postwean males at 25.0 mg/kg/d exhibited normal BW gain and increasing grip strength over time. Therefore, AM caused maternal toxicity; offspring effects during lactation were consistent with inanition from maternal toxicity. Postwean males exhibited recovery with no signs of AM-mediated toxicity. These results do not support the conclusions of Husain et al.

Serine-enhanced restoration of 2-methoxyethanol-induced dysmorphogenesis in the rat embryo and near-term fetus.

Effects of serine on restorative growth were characterized by comparing embryo/fetal responses after maternal exposure to 2-methoxyethanol (ME) and ME + serine by gavage on gestation day (gd) 13, a day of heightened limb sensitivity. Paws (gd 20) and limb buds (gd 15) were examined after ME alone at 50, 100, and 250 mg/kg, and after ME (either 100 or 250 mg ME/kg) + serine (1734 mg serine/kg) administered within minutes (0 hr) to 24 hr after ME. Paw development was not altered after ME at 100 mg/kg, but was highly sensitive to 250 mg ME/kg with all fetuses and litters exhibiting defects (ectrodactyly, syndactyly, and short digit) in the preaxial region. In contrast, the limb bud displayed dose-related incidences of abnormalities after maternal treatment with the low and high levels of ME. The condensing (precartilaginous, pentadactyl pattern) and noncondensing (undifferentiated mesenchymal cells) regions exhibited changes in their size, number, and location. Serine administration after 250 mg ME/kg was effective in reducing the occurrence of paw dysmorphogenesis with its protection potency inversely related to its delay of administration (i.e., 0% paw defect incidence after 0-hr delay, 25% after 4-hr delay, 41-45% after 8- and 12-hr delays, and 76% after 24-hr delay). The occurrences of limb bud pattern disturbances produced by ME were also markedly decreased by serine cotreatment. Higher incidences of embryonic defects versus those of fetal defects demonstrate that restorative growth followed ME exposure. Serine attenuation of ME teratogenicity appears to emanate from enhanced restorative growth so that tissue damage, which otherwise would be expressed as a defect at parturition, is repaired and replaced to resume development of the limb toward its normal structure.

Multiple choice questions: to guess or not to guess.

Multiple choice question papers in which the student has a 'don't know' option are widely used in undergraduate and postgraduate examinations in Medicine. In the present study students' performance in papers with a 'don't know' option has been compared with their performance when they are instructed to answer all the questions. By completing questions left unanswered (i.e. 'don't know' options) students were able to increase their score significantly and the rank order of the students in class is changed. Answers omitted may indicate complete ignorance or various degrees of knowledge. It is concluded that the 'don't know' option in multiple choice question papers favours the bold and test-wise student and in consequence their validity as a measure of achievement may suffer. Papers in which the student is instructed to answer all the questions are to be preferred to those in common use where there is a 'don't know' option.