Analysis of dioxins, furans and DL-PCBs in food and feed samples from Lithuania and estimation of human intake.

The methods, validated for determination of dibenzo-p-dioxins, dibenzofurans and dioxin like-polychlorinated biphenyls were applied for investigation of food and feed matrixes. Validation criteria on repeatability and reproducibility conditions comply with the requirements of European Commission. Validated methods were successfully applied for determination of PCDD/F and DL-PCB in fish, meat and feed using HRGC-HRMS. Statistical data was evaluated. One focal point of this work was to determine a fit for dioxins, furans and DL-PCBs of fatty fish for human consumption from the Baltic Sea ICES 26. Daily intake was found to be in the range of 2-4 TEQ pg/kg body weight and it is in the range of recommended TDI of 1-4 TEQ pg/kg body weight. The range of Baltic cod liver was 2-4 pg TEQ kgbw(-1)d(-1) WHO-TEQ((1998)) PCDD/F, PCB and its consumption was forbidden in Lithuania in 2011. Baltic fish represents 97.9% of human daily intake. Other matrixes like meat, eggs and feed did not exceed the maximum limit set by EU during the period of 2005-2011.

Disubstituted indazoles as potent antagonists of the integrin alpha(v)beta(3).

A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC(50) 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

Terphenyl cyclooxygenase-2 (COX-2) inhibitors: optimization of the central ring and o-biphenyl analogs.

The discovery of terphenyl derivatives as highly selective COX-2 inhibitors resulted from our efforts to overcome poor pharmacokinetics demonstrated by the COX-2 selective diarylthiophene DuP 697 [2-bromo-4-(4'-sulfonylmethyl)phenyl-5-(4'-fluoro)phenylthiophe ne]. Detailed SAR related to the ortho-biphenyls and variants of the central ring are described herein.

Rapid synthesis of RGD mimetics with isoxazoline scaffolds on solid phase: identification of alphavbeta3 antagonists lead compounds.

Isoxazoline containing RGD mimetics were rapidly synthesized on a solid phase to optimize linkers, regioisomers of isoxazoline scaffolds, and exosite binding groups to yield lead alphavbeta3 antagonists.

Psychosocial risk and protective factors for adolescent tobacco use.

Knowledge of risk and protective factors for adolescent tobacco use will lead to the development of improved intervention strategies to reduce/prevent tobacco use. Theory and empirical findings demonstrate the multivariate complexity of the etiology of tobacco use. Sociocultural, social/interpersonal, and intrapersonal factors act through mediated chains of ultimate, distal, and proximal influences. Some influences moderate the effects of others. Once tobacco is used, feedback mechanisms modify prior causes that in turn alter subsequent tobacco use behavior. Most theories and cross-sectional, prospective, and causal process studies have contained major limitations: (a) most addressed only small portions of the total picture; (b) most mediational studies did not test for interactions and most moderation studies are based on limited theory (if any); and (c) most theories do not discuss how the causal processes might be different for males and females or for different ethnic groups (special cases of moderation). Furthermore, few studies focused on more distal or ultimate influences or examined multi-stream patterns, and few theories or causal process studies have specified or tested feedback loops. Determining psychosocial risk factors and how they influence tobacco use faces several major challenges, including discovering complex mediating processes, moderating variables, and overcoming limitations of surveys and theory. We offer six recommendations to advance transdisciplinary tobacco-prevention research: (a) base future studies on strong theory and aim to test one or more theories or theoretically derived hypotheses; (b) collect four or more waves of data and adopt dynamic strategies of prediction and analysis, including interactions, indirect effects, feedback loops, and transitions from one level of tobacco use to another; (c) provide evidence of generalizability to sub-populations within the study sample, such as by gender, ethnic group, and socioeconomic status; (d) use high-quality measures and multiple methodologies, including non-panel longitudinal studies, intensive interview, ethnography, experimental intervention, and small exploratory studies as well as further prospective studies; (e) include variables from multiple streams of influence to investigate interrelationships among cultural, social, and intrapersonal factors; and (f) collect data from multiple nested units (e.g., children within families, within schools, within neighborhoods) and employ multi-level analysis methods to investigate interrelationships among ultimate, distal, and proximal variables.

Illicit substance use among adolescents: a matrix of prospective predictors.

This paper reviews findings from 58 prospective studies of illicit substance use (ISU) among adolescents. It arranges 384 findings according to three types of influence (viz., social, attitudinal, and intrapersonal) and four levels of influence (viz., ultimate, distal, proximal, and immediate). The bulk of evidence reconfirms the importance of several predictors of ISU (e.g., intentions and prior substance-related behavior, friendship patterns and peer behaviors, absence of supportive parents, psychological temperament), reveals that a few variables thought to be well-established predictors may not be (e.g., parental behaviors, parental permissiveness, depression, low self-esteem), and uncovers several variables where findings were either sparse or inconsistent (e.g., the role of public policies concerning ISU, mass media depictions of ISU, certain parenting styles, affective states, perceptions of parental disapproval for ISU, and substance-specific refusal skills). Directions for future research are discussed.

Sociopsychological correlates of motivation to quit smoking among low-SES African American women.

This article examines correlates of desire and plans to quit smoking among 248 young, low-socioeconomic status African American women, using variables derived from the health belief model (HBM) and the theory of reasoned action. Consistent with these theoretical models, stronger concern about the effect of smoking on one's health and having close others who want the smoker to quit increased motivation to quit smoking. However, motivation was not associated with specific HBM components regarding lung cancer. Heavier smoking and stronger perceptions regarding the functional utility of smoking decreased motivation to quit, but not as much as expected in this study population. Consistent with a process of change approach to smoking cessation, the factors that moved smokers from not planning to planning to ever quit were different from factors associated with further motivation level among the smokers who did plan to ever quit.

The MAPK cascade is required for mammalian associative learning.

Mitogen-activated protein kinase (MAPK) is an integral component of cellular signaling during mitogenesis and differentiation of mitotic cells. Recently MAPK activation in post-mitotic cells has been implicated in hippocampal long-term potentiation (LTP), a potential cellular mechanism of learning and memory. Here we investigate the involvement of MAPK in learning and memory in behaving animals. MAPK activation increased in the rat hippocampus after an associative learning task, contextual fear conditioning. Two other protein kinases known to be activated during hippocampal LTP, protein kinase C and alpha-calcium/calmodulin protein kinase II, also were activated in the hippocampus after learning. Inhibition of the specific upstream activator of MAPK, MAPK kinase (MEK), blocked fear conditioning. Thus, classical conditioning in mammals activates MAPK, which is necessary for consolidation of the resultant learning.

Structure-activity relationships (SAR) of some tetracyclic heterocycles related to the immunosuppressive agent Brequinar Sodium.

The structure-activity relationships of some tetracyclic heterocycles related to Brequinar were explored. Activities as inhibitors of dihydroorotate dehydrogenase and the mixed lymphocyte reaction are related to ring system, heteroatom placement, and pendant ring substitution.

Heteroatom- and carbon-linked biphenyl analogs of Brequinar as immunosuppressive agents.

Structure-activity relationships were explored for some analogs of Brequinar having a linking atom between the 2-biphenyl substituent and the quinoline ring. Activities as inhibitors of dihydroorotate dehydrogenase and the mixed lymphocyte reaction were related to the overall shape and lipophilicity of the 2-substituent.

2,5-Diarylisothiazolone: novel inhibitors of cytokine-induced cartilage destruction.

A series of 2,5-diarylisothiazolones is reported that inhibit the IL-1 beta-induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, nonpeptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases.

Estimating individual influences of behavioral intentions: an application of random-effects modeling to the theory of reasoned action.

Methods are proposed and described for estimating the degree to which relations among variables vary at the individual level. As an example of the methods, M. Fishbein and I. Ajzen's (1975; I. Ajzen & M. Fishbein, 1980) theory of reasoned action is examined, which posits first that an individual's behavioral intentions are a function of 2 components: the individual's attitudes toward the behavior and the subjective norms as perceived by the individual. A second component of their theory is that individuals may weight these 2 components differently in assessing their behavioral intentions. This article illustrates the use of empirical Bayes methods based on a random-effects regression model to estimate these individual influences, estimating an individual's weighting of both of these components (attitudes toward the behavior and subjective norms) in relation to their behavioral intentions. This method can be used when an individual's behavioral intentions, subjective norms, and attitudes toward the behavior are all repeatedly measured. In this case, the empirical Bayes estimates are derived as a function of the data from the individual, strengthened by the overall sample data.

Metabolism resistant isothiazolone inhibitors of cartilage breakdown.

A series of 2-(arylmethyl)pyridoisothiazolones is reported that inhibit the IL-1 beta induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, non-peptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases.

Reviewing theories of adolescent substance use: organizing pieces in the puzzle.

This article reviews 14 multivariate theories of experimental substance use (e.g., alcohol and marijuana use) among adolescents, including those theories that emphasize (a) substance-specific cognitions, (b) social learning processes, (c) commitment to conventional values and attachment to families, and (d) intrapersonal processes. Important similarities and differences among these theories are addressed, as are the conceptual boundaries of each theory. In an attempt to integrate existing theories, a framework is proposed that organizes their central constructs into 3 distinct types of influence (viz., social, attitudinal, and intrapersonal) and 3 distinct levels of influence (viz., proximal, distal, and ultimate). Implications for future theory development are discussed.

Differential influence of parental smoking and friends' smoking on adolescent initiation and escalation of smoking.

Smoking-related behaviors and attitudes of significant others (especially friends and parents) are among the most consistent predictors of adolescent smoking. However, theorists remain divided on whether the behaviors of significant others influence adolescent smoking directly or indirectly, and the relative influence of parental and peer smoking on adolescents' own smoking is still a matter of debate. In addition, little research has examined the role of significant others' behavior on different stages of smoking onset. In particular, not much information is available regarding gender and ethnic differences in social influences on smoking behavior. We use structural equation modeling to address these issues. Different theoretical perspectives from cognitive-affective theories (Ajzen 1985; Ajzen and Fishbein 1980) and social learning theories (Akers et al. 1979; Bandura 1969, 1982, 1986) have been integrated into a structural model of smoking influence. The results show that friends' smoking affects adolescent initiation into smoking both directly and indirectly, whereas parental smoking influences smoking initiation only indirectly. The data also show that friends' and parents' smoking affect smoking escalation only indirectly. In general, friends' smoking has a stronger effect on adolescents' smoking behavior, particularly on initiation. Multiple group comparisons of the structural models predicting smoking initiation among males and females reveal that parental approval of smoking plays a significant mediating role for females, but not for males. Comparisons of Whites, Blacks, Hispanics, and other ethnic groups reveal that there are some significant differences in the pathways of friends' influences among the four groups.

Heteroaryl-fused 2-phenylisothiazolone inhibitors of cartilage breakdown.

The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1 beta stimulation. Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases. To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.

Joining the front line against HIV: an education program for adult probationers.

This article describes the implementation and evaluation of a human immunodeficiency virus (HIV) education program for adult offenders. Samples of Cook County (Chicago) probationers were educated about either HIV or heart disease in small group and in one-on-one sessions. The evaluation employed a 2 x 2 factorial design. Data were collected at 3 points in time: during a pretest, posttest, and follow-up. Results showed that offenders' knowledge of HIV was increased significantly at posttest and follow-up. Although the HIV presentation increased knowledge significantly, it had little impact on HIV-related behavioral intentions at posttest or on actual prevention behaviors at follow-up. The implications of these findings are discussed with respect to HIV education programs in criminal justice settings.

2-substituted-1-naphthols as potent 5-lipoxygenase inhibitors with topical antiinflammatory activity.

The synthesis, biological evaluation, and structure-activity relationships of a series of 1-naphthols bearing carbon substituents at the 2-position are described. These compounds are potent inhibitors of the 5-lipoxygenase from RBL-1 cells and also inhibit bovine seminal vesicle cyclooxygenase. Structure-activity relationships for these two enzymes are different, implying specific enzyme inhibition rather than a nonspecific antioxidant effect. 2-(Aryl-methyl)-1-naphthols are among the most potent 5-lipoxygenase inhibitors reported (IC50 values generally 0.01-0.2 microM) and show excellent antiinflammatory potency in the mouse arachidonic acid ear edema model. To study the effects of structure on in vitro and in vivo activity, four general features of the molecules were varied: the 2-substituent, the 1-hydroxyl group, substitution on the naphthalene rings, and the 1,2-disubstituted naphthalene unit itself. 2-Benzyl-1-naphthol (5a, DuP 654) shows a very attractive profile of topical antiinflammatory activity and is currently in clinical trials as a topically applied antipsoriatic agent.

Treatment opportunities on a consultation/liaison service.

The amount of time consultation psychiatrists in a large metropolitan teaching hospital spent providing direct services was studied over 1,104 consecutive consultation cases. Although the majority of cases required less than 5 hours of psychiatric time apiece, more than 10% of these cases each received more than 10 hours of direct services. This finding has important implications for understanding the types of psychiatric services provided to hospitalized medical/surgical patients.