ESR1 polymorphisms, daily hassles, anger expression, and depressive symptoms in adolescent boys and girls.

Studies reporting associations between genetic factors and mood-related traits have often been criticized (i) for failing to take into account the role of the social environment in which individuals act and (ii) for not maintaining a 'transparent narrative connection' between genes and outcomes. In a sample of adolescents, we analyzed whether PvuII and XbaI, two polymorphisms on the ESR1 (Estrogen Receptor Gene α) were related to depressive symptoms, and considered whether daily hassles moderated this relationship and whether anger expression style mediated this relationship. Analyses suggested that ESR1 polymorphisms are relevant to the intra-sexual variability in depressive symptoms in boys and that the experience of daily hassles moderated this relationship. No such relationships were found in girls. Additionally, ESR1 polymorphisms are related to anger expression styles in girls. Anger-related variables, however, did not mediate the relationship between ESR1 polymorphisms and depressive symptoms, in boys nor in girls.

Complexities of particulate matter measurement in parenteral formulations of small-molecule amphiphilic drugs.

Reconstituted parenteral solutions of three surface-active anti-infective small-molecule drugs and solutions of sodium dodecyl sulfate (SDS, a model surfactant) were studied to quantify the impact of sample preparation and handling on particle counts. Turbidimetry and light obscuration profiles were recorded as a function of agitation and shearing with and without the introduction of foam into the solutions. SDS solutions at concentrations above the critical micelle concentration (CMC) show significantly greater sensitivity to shear and foam presence than SDS solution below the CMC: Values of >10 µm particles increased 8 fold over control (an unsheared sample) in the micellar solution vs. 4 fold particle count increase over control at a sub-micellar concentration. An even more significant increase in the ratio of particle count in sheared/unsheared solution is seen for >25 µm unit counts, due to the increased interference of foam with the measurement. Two commercial products, injection formulations of teicoplanin and cefotaxime sodium, as well as an investigational compound 1, showed an increase in scattering as a function of foam production. The impact of foaming was significant, resulting in an increase of turbidity and light obscuration measurements in all solutions. The results illustrate some of the challenges that are inherent to optically clear, homogeneous pharmaceutical injections containing compounds which have a tendency toward self-association and surfactant-like behavior.

Gender ideology, same-sex peer group affiliation and the relationship between testosterone and dominance in adolescent boys and girls.

Although the role of testosterone in the aetiology of social dominance is often suggested, surprisingly few studies have addressed the relationship between sex steroid hormones and dominance as a personality trait. In this paper, the relationship between testosterone and dominance is studied in a sample of adolescent boys and girls, taking into account the moderating role of gender ideology and same-sex peer group orientation. A direct association between free testosterone (FT) and dominance was found in girls but not in boys. In boys, masculine ideology moderated the relationship between FT and dominance, while in girls the relationship between FT and dominance was moderated by same-sex peer group affiliation.

Estradiol, testosterone, differential association and aggressive and non-aggressive risk-taking in adolescent girls.

Although the relation between androgens and adolescent risk-taking has been relatively well documented in boys, little is known as to how sex steroid hormones relate to aggressive (ART) and/or non-aggressive adolescent risk-taking (NART) behavior in girls. On the basis of a sample of 298 adolescent girls (mean age: 14.3 years), we examined: (i) the relationship between serum levels of testosterone (T) and estradiol (E2) in relation to ART and NART and (ii) if differential association--having friends who are highly involved in risk-taking--moderates the relationship between relationships between hormones and risk-taking. The sample provided evidence of an association between free estradiol (FE2) and both NART (Beta=0.19; p<0.01) and ART (Beta=0.19; p<0.01), controlling for age and pubertal development. No relationship between T and ART or NART was found. The importance of the relationship between E2 and ART and NART differed between girls at different phases of their menstrual cycle and was significant only for girls in the mid-phase of the menstrual cycle. In addition, significant interactions between differential association and FE2 were found indicating that the relationship between FE2 and NART and ART was particularly strong in girls with high levels of differential association.

2d:4d, sex steroid hormones and human psychological sex differences.

Studies on 2d:4d, the ratio between the second and the fourth digit, as a possible indicator of prenatal androgen exposure, have failed to produce consistent results. This paper analyzes the relation between 2d:4d, sex steroids and well-documented sex differences in characteristics such as depression, dominance, and aggressive (ART) and non-aggressive adolescent risk-taking (NART) in a comparatively large sample of adolescent boys (N=301, mean age: 14.4 years) and girls (N=298, mean age: 14.3 years). Boys had on average a lower 2d:4d than girls (F=42.15; p<0.001). With respect to boys, controlling for age and pubertal development (PD), a small but marginally significant positive association was found between 2d:4d and total testosterone (TT) (r=0.11; p<0.05). In girls a significant association was found between 2d:4d and SHBG (r=0.18; p<0.01). However, relationships between 2d:4d and hormones depended on the phase of the menstrual cycle, with 2d:4d being negatively associated with FT (B=-0.013; p<0.05) once a positive association between 2d:4d and FT for girls in the mid-cycle group (B=0.019; p<0.01) is taken into account. With respect to sex differences in characteristics, we found evidence of a relationship between 2d:4d and depression in boys (r=-0.14; p<0.05) but not between 2d:4d and dominance, ART or NART. No relationships were found between 2d:4d and any of these variables in girls.

Liquid chromatographic method for analysis of saponins in Maesa balansae extract active against leishmaniasis.

A liquid chromatographic method was developed for the separation of six related triterpenoid saponins in Maesa balansae extracts with different purity, active against leishmaniasis. As stationary phase a Hypersil BDS C18 column (3 microm), 100 x 4.6 mm was used. The mobile phase was a mixture of methanol, acetonitrile, 5% (m/v) ammonium acetate, pH 6.5 and water. A linear gradient was developed for the analysis of crude extracts. An isocratic method was developed to analyze purified samples that mainly contained saponins 3 and 4, the most active saponins. The isocratic LC method was optimized and the robustness was evaluated with an experimental design. The method showed good selectivity, repeatability, linearity and sensitivity.

Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males.

OBJECTIVES: Androgen activity has been implicated in a range of traits and behaviours that have well-documented sex differences. However, the results of the studies on the relationship between testosterone and these traits and behaviours are inconsistent. This study has analyzed i) whether CAG repeat length, a presumed modulator of androgen receptor sensitivity, is associated with sex-dimorphic traits and behaviours (aggressive and non-aggressive risk-taking (ART and NART), dominance, depressive symptoms and self-esteem), and ii) whether CAG repeat length interacts with free testosterone (FT) with respect to these traits and behaviours. DESIGN AND METHODS: Data obtained from a group of adolescent boys (n=301; mean age: 14.4 years) were analyzed using multivariate general linear modelling (SPSS, Chicago, IL, USA 15.0). RESULTS: We found no direct correlation between CAG repeat length and dependent variables. We found significant interactions between CAG repeat length and testosterone, indicating that FT was more positively related to ART and NART with a shorter repeat length, and that an inverse association of FT with depressive symptoms and a positive association with self-esteem were stronger in boys with a longer CAG repeat length. CONCLUSION: Our findings indicate the importance of studying FT and CAG repeat length simultaneously with respect to sex-dimorphic traits, taking into account the possible interactions between the two.

The role of testosterone in aggressive and non-aggressive risk-taking in adolescent boys.

While there exists increasing evidence of a relationship between testosterone (T) and risk-taking (RT), many issues remain unsolved. This paper tries to address two main-questions: (i) does T influence aggressive risk-taking (ART) and/or non-aggressive risk-taking (NART) behavior and (ii) is this relationship stable throughout age and pubertal development and how is the relationship affected by affiliations with peers that are highly involved in RT, referred to as differential association (DA)? For a sample of 301 third-grade adolescent boys (mean age 14.4 years), we assessed the relationship between serum levels of T and estradiol (E2), DA and ART/NART. Significant effects of SHBG (Beta=-0.15; p<0.029) and free testosterone (FT) (Beta=0.23; p<0.003) on NART were shown. No significant effects were found with respect to ART. Further analyses showed that the FT-NART and the FT-ART relations differed as to age but not as to pubertal development (PD) and that the relationship between FT and RT is mediated by DA as such that individuals with higher levels of FT have friends that are more involved in RT and their influence contributes to increased levels of RT. Our results indicate that hormone-related interests and predispositions may influence the development of affiliations with risk-taking peers, a factor which is crucial in understanding adolescent RT.

Compatibility of ceftobiprole medocaril with selected drugs during simulated Y-site administration.

PURPOSE: The physical compatibility of the new cephalosporin ceftobiprole medocaril with 70 other drugs during simulated Y-site injection was studied. METHODS: Ceftobiprole was reconstituted with sterile water for injection. Dilutions of ceftobiprole 2 mg/mL (as ceftobiprole medocaril 2.67 mg/mL) were prepared in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection. For testing compatibility with the other drugs, a 5-mL sample of the ceftobiprole 2-mg/mL admixtures was combined with a 5-mL sample of the other drug either undiluted or diluted with one of the three vehicles. Each combination was prepared in duplicate, switching the order of drug addition, and kept at room temperature. At intervals up to four hours after preparation, samples were examined visually and with the aid of a Tyndall beam and measured with a turbidimeter and a particle sizer and counter. Compatibility with propofol was evaluated by checking for emulsion separation and particles after centrifugation. RESULTS: In all three vehicles, ceftobiprole was compatible with 31 other drugs and incompatible with 32. With 7 drugs, compatibility was dependent on the vehicle used. Signs of incompatibility included the presence of visible and subvisible particles, haze, and turbidity. No incompatibilities were related to the order of mixing. CONCLUSION: Of the 70 drugs evaluated for compatibility with ceftobiprole 2 mg/ mL (as medocaril) in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection, 31 were found to be compatible and 32 were found to be incompatible in all three of the infusion solutions. For 7 of the drugs, compatibility was dependent on which infusion solution was used. Ceftobiprole medocaril should not be simultaneously administered via a Y site with drugs with which it was shown to be incompatible.

Development of a capillary electrophoretic method for the separation of diastereoisomers of a new human immunodeficiency virus protease inhibitor.

A capillary electrophoretic (CE) method was developed for the separation of diastereoisomers of a new human immunodeficiency virus (HIV) protease inhibitor TMC114. In total 16 isomers of this drug have been synthesized (eight pairs of enantiomers). We succeeded in the separation of the eight diastereoisomers, but no enantiomers could be separated. Because of the high similarity and water-insolubility of these isomers, the separation is a real challenge. Different CE modes were tried out: capillary zone electrophoresis (CZE), nonaqueous capillary electrophoresis (NACE), micellar electrokinetic capillary chromatography (MEKC), and microemulsion electrokinetic capillary chromatography (MEEKC). Only MEEKC offered resolution of these compounds.