Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood.

Critical periods are temporary windows of heightened neural plasticity early in development. For example, fear memories in juvenile rodents are subject to erasure following extinction training, while after closure of this critical period, extinction training only temporarily and weakly suppresses fear memories. Persistence of fear memories is important for survival, but the inability to effectively adapt to the trauma is a characteristic of post-traumatic stress disorder (PTSD). We examined whether Nogo Receptor 1 (NgR1) regulates the plasticity associated with fear extinction. The loss of NgR1 function in adulthood eliminates spontaneous fear recovery and fear renewal, with a restoration of fear reacquisition rate equal to that of naive mice; thus, mimicking the phenotype observed in juvenile rodents. Regional gene disruption demonstrates that NgR1 expression is required in both the basolateral amygdala (BLA) and infralimbic (IL) cortex to prevent fear erasure. NgR1 expression by parvalbumin expressing interneurons is essential for limiting extinction-dependent plasticity. NgR1 gene deletion enhances anatomical changes of inhibitory synapse markers after extinction training. Thus, NgR1 robustly inhibits elimination of fear expression in the adult brain and could serve as a therapeutic target for anxiety disorders, such as PTSD.

Substance use and other factors associated with risky sexual behavior among pregnant adolescents.

A study of the relationship between substance use and risky sexual behavior was conducted among 241 unmarried pregnant adolescents aged 17 and younger who lived in a metropolitan area in the Northwest. The respondents had comparable or higher lifetime use rates for all substances than did women in a national sample of high school seniors, even though the pregnant adolescents were younger. Ninety-four percent had used alcohol, 78% marijuana, 30% cocaine and 30% stimulants, compared with 92%, 48%, 14% and 23%, respectively, among women in the national sample. Among the pregnant adolescents, 84% had had more than one sexual partner, 39% had had a sexually transmitted disease and 60% had used contraceptives during less than half of their sexual encounters. At the bivariate level, use of cigarettes and alcohol in general and use of alcohol and drugs during sex were positively associated with risky sexual behavior. However, when other characteristics associated with risky sexual behavior--family bonding, parental monitoring, commitment to conventional values, peer associations, self-esteem and delinquent activities--were included in the multivariate analysis, the effect of substance use disappeared.

PIP: Among adolescents, rates of premarital intercourse have increased, age at first intercourse has decreased, and couples are delaying marriage to a greater extent since the 1970s. These factors effectively combine to increase the risk of female adolescents becoming pregnant and/or infected with sexually transmitted diseases (STD). As might be expected, birth and STD rates have also increased dramatically over the past two decades, confirming that youths continue to engage in unprotected sexual activity. Pregnant adolescents deserve particular attention from prevention interventions, for they show tangible evidence of a history of unprotected sexual activity. This study specifically considers risky sex behavior within a target group of 241 urban, unmarried pregnant adolescents aged 17 and younger and the behavioral relationship with substance use. Compared to women from a national sample of high school seniors, these pregnant women had higher or comparable lifetime use rates for all substances. 94% had used alcohol, 78% marijuana, 30% cocaine, and 30% stimulants compared to 92%, 48% 14%, and 23%, respectively, among women in the national sample. 84% of pregnant adolescents had had more than one sexual partner, 39% had had an STD, and 60% had used contraception in less than half their sexual encounters. Further, 70% ran away from home before pregnancy, 62% were suspended or expelled from school, and 24% served time in jail/detention. Cigarettes and alcohol in general, and alcohol and drug use during sex, were positively associated with risky sexual behavior. The effect of substance use, however, disappeared when controlling through multivariate analysis for family bonding, parental monitoring, commitment to conventional values, peer associations, self-esteem, and delinquent activities. These results suggest that both substance use and increased risk of pregnancy in the study sample may be associated with a syndrome of problem behaviors and life circumstances. While more research is needed, it appears that the messages "just say no" and "always use condoms" will be inadequate to bring about positive change.

Factors related to substance use by pregnant, school-age adolescents.

This study provides information on substance use among pregnant adolescents, and examines social influence, intrapersonal, and environmental factors associated with substance use during pregnancy in adolescence. The sample consists of premaritally pregnant adolescents (N = 241), who were interviewed as part of a longitudinal study of patterns of drug use among pregnant and parenting school-age adolescents. The findings indicate that, although the sample demonstrated a high rate of prepregnancy substance use, a significant drop in use occurred during pregnancy. Logistic regression analysis indicated that perceived harm of using substances while pregnant, best friend's substance use, boyfriend's substance use, and school status were related to substance use during pregnancy, even after controlling for the effects of prepregnancy substance use. The findings have implications for substance use prevention and intervention programs for pregnant and parenting adolescents.

Attitudes and adolescent nonmarital childbearing: evidence from the National Longitudinal Survey of Youth.

PIP: The 1979 National Longitudinal Survey of Youth (NLSY) provided data for the analysis of the impact of self-esteem, locus of control, attitudes towards women's family roles, work, and school on the probability of a nonmarital birth. The study avoided methodological problems of prior studies by using a national data base with attitude measured before nonmarital childbearing occurs. No prior studies included these 5 factors. Previous research on attitudes and nonmarital childbearing is summarized. Theoretical models imply that self-esteem, high educational goals, and an internal locus of control are associated with a lower likelihood of a nonmarital birth. The conceptual model for this study is described. It does not include how attitudes develop or estimate the linkage between family background variables and attitudes. A reduced from approach was used and controls were included for 6 family background and personal variables. The sample of 1184 girls was restricted to those aged 14 or 15 years in 1979 who were never married or had a child. 16.9% of the sample had a nonmarital child by 19 years. Measurement of explanatory variables is indicated as the Rosenberg Self Esteem Scale and the Rotter scale for internal-external locus of control. A 7-item scale measured women's roles, an 8-item scale measured attitudes toward school, and 3 items assessed views on the importance of improving one's employment prospects. Background control variables were race/ethnicity, mother's education, presence of welfare income, family income, family structure, and religiosity. The standard logistics technique was used to estimate the logarithm of the odds of having a nonmarital birth as a linear function of both attitude and family background variables. Models were estimated both with and without the educational expectation variable. The results appear to indicate that self-esteem and attitudes toward school are associated with nonmarital childbearing, as predicted by theory. Locus of control does not systematically affect the likelihood of nonmarital childbearing, nor do family and gender roles and attitudes toward work. Educational expectations are not associated, but may act as an intervening variable.^ieng

Biologic activity of human chorionic gonadotropin following reversed-phase high-performance liquid chromatography.

Human chorionic gonadotropin (hCG) was analyzed by reversed-phase high-performance liquid chromatography (HPLC) using mobile phases previously described in the literature, as well as newly developed solvent systems. Fractions of hCG collected following reversed-phase HPLC were bioassayed by activation of adenylate cyclase to determine their biologic potencies. hCG retained only 10-60% of its biologic activity following reversed-phase HPLC, depending on the chromatographic conditions employed. A portion of the reduced biologic activity was attributed to dissociation of the alpha- and beta-subunits of hCG at the low pH of the mobile phases, since neutralization of the pH prior to lyophilization and bioassay increased the biologic potency of the chromatographed hormone. The remaining loss in biologic activity is presumably due to organic solvent denaturation.

Continuous flow bead-bed dissolution apparatus for suppositories.

A bead-bed dissolution apparatus for suppositories was evaluated by measuring the release of benzocaine from various vehicles. During dissolution, suppositories soften, deform, disintegrate, and eventually pass through a phase change from a solid to an oil. The control of the interfacial area during dissolution is a key factor in obtaining experimentally reproducible release data. The proposed suppository dissolution apparatus was designed to provide greater constancy of the exposed suppository area for dissolution. The apparatus consisted of a glass bead-bed containing the suppository. A continuous flow of liquid was passed through the bead-bed at a constant rate. Direct contact of the suppository was maintained with the dissolution medium, confining the suppository within the beads.

Transport of prostaglandins through silicone rubber.

The in vitro release profiles of the F-series of prostaglandins were determined from a silicone rubber matrix of constant surface area. Silicone rubber was selective toward prostaglandin transport and offers potential as a controlled-release delivery system. Drug release patterns were dependent on the lipophilicity of the prostaglandin molecule. For dinoprost (prostaglandin F2 alpha), the following sequences was observed: methyl ester greater than free acid greater than tromethamine salt. The biologically potent carboprost methyl [(15S)-15-methylprostaglandin F2 alpha methyl ester] was release considerably faster than the methyl ester of the parent dinoprost molecule, while release of the tromethamine salt of the two prostaglandins was similar. Permeability rates of the salts were depressed substantially when compared to their respective C-1 methyl esters. Results from independent membrane transport studies supported the observed dependence of steady-state flux on the chemical structure of the prostaglandin molecule. Plots of the amount released per unit area versus the square root of time were linear except for the initial drug release phase, and the total amount of prostaglandin released increased as the initial loading dose was raised. The data were analyzed according to a physical model describing drug release from inert matrix systems. The observed concentration dependence was consistent with the predictions of the model.

High-pressure liquid chromatographic determination of the 15-epimer of dinoprost in bulk drug.

The p-nitrophenacyl esters of dinoprost and its 15-epimer are well resolved using high-pressure liquid chromatography. Quantitation was achieved using the internal standard technique. The specially synthesized diphenylurea ester of cholic acid was found to be a model internal standard. Graphs of peak height ratios of the prostaglandin to the internal standard were linear with respect to the amount of prostaglandin injected, with the lower detection limit of the 15-epimer being about 0.5%. Data are presented that demonstrate the usefulness of this analytical technique in determining the concentration of the 15-epimer present during studies on the kinetics of decomposition of dinoprost.