Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis.

We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC(50) values of 32.02 microM and 1.39 microM, respectively. SCH or GOM at concentrations up to 100 microM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake.

Neuroprotective potential of ceftriaxone in in vitro models of stroke.

Astrocytic glutamate transporters are considered an important target for neuroprotective therapies as the function of these transporters is abnormal in stroke and other neurological disorders associated with excitotoxicity. Recently, Rothstein et al., [Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433:73-77] reported that beta-lactam antibiotics (including ceftriaxone, which easily crosses the blood-brain barrier) increase glutamate transporter 1 (GLT-1) expression and reduce cell death resulting from oxygen-glucose deprivation (OGD) in dissociated embryonic cortical cultures. To determine whether a similar neuroprotective mechanism operates in more mature neurons, which show a different pattern of response to ischemia than primary cultures, we exposed acute hippocampal slices obtained from rats treated with ceftriaxone for 5 days (200 mg/kg; i.p.) to OGD. Whole-cell patch clamp recording of glutamate-induced N-methyl-d-aspartate (NMDA) currents from CA1 pyramidal neurons showed a larger potentiation of these currents after application of 15 microM dl-threo-beta-benzyloxyaspartic acid (TBOA; a potent blocker of glutamate transporters) in ceftriaxone-injected animals than in untreated animals, indicating increased glutamate transporter activity. Western blot analysis did not reveal GLT-1 upregulation in the hippocampus. Delay to OGD-induced hypoxic spreading depression (HSD) recorded in slices obtained from ceftriaxone-treated rats was longer (6.3+/-0.2 vs. 5.2+/-0.2 min; P<0.001) than that in the control group, demonstrating a neuroprotective action of the antibiotic in this model. The effect of ceftriaxone was also tested in organotypic hippocampal slices obtained from P7-9 rats (>14 days in vitro). OGD or glutamate (3.5-5.0 mM) damaged CA1 pyramidal neurons as assessed by propidium iodide (PI) fluorescence. Similar damage was observed after pre-treatment with ceftriaxone (10-200 microM; 5 days) and ceftriaxone exposure did not result in GLT-1 upregulation as assayed by Western blot. Treatment of slice cultures with dibutyryl cAMP (100-250 microM; 5 days) increased GLT-1 expression but did not reduce cell damage induced by OGD or glutamate. Thus we confirm the neuroprotective effect of antibiotic exposure on OGD-induced injury, but suggest that this action is related to independent modulation of transporter activity rather than to the level of GLT-1 protein expression. In addition, our results indicate that the protective effects of beta-lactam antibiotics are highly dependent on the experimental model.

Effect of organic waste amendments on degradation of PAHs in soil using thermophillic composting.

The feasibility of using various types of organic wastes including pig manure, sewage sludge, and soybean refuse for remediation of soil spiked with phenanthrene, anthracene and pyrene (PAHs) was evaluated through batch-scale composting reactors. The most active degradation of PAHs occurred between day 4 to 30 and maximum removal at the end of composting accounted for 90% of the initial concentrations of the three PAH compounds. Among the three PAHs, degradation of pyrene in the composting mass was relatively slow as indicated by a longer lag period than that of phenanthrene and anthracene. This corresponded well with the high molecular weight and log K(ow) values of pyrene. The organic amendments were effective in enhancing the degradation of PAHs, and pig manure amendment exhibited a slightly higher removal efficiency than sewage sludge and soybean refuse. A decrease in total organic matter in all treatments indicated that the decomposition process occurred. Toxicity test with cress seed germination was evaluated and no phytotoxicity was noted after 21 days of composting. This preliminary study positively supports that pig manure is an effective organic additive for bioremediation of PAH-contaminated soil using composting as a treatment technology.

Pig manure as a co-composting material for biodegradation of PAH-contaminated soil.

Pig manure at three different ratios of 12.5%, 25% and 50% (w/w dry weight basis) was amended with a soil spiked with 100 mg kg(-1) each of three polycyclic aromatic hydrocarbons (phenanthrene, anthracene, and pyrene) to investigate its effect on the biodegradation of these PAHs in a bench-scale composting system. An increase in pig manure amendment was effective in enhancing the amounts of soluble organic carbon, ammoniacal nitrogen, and soluble phosphorous in the composting mass. It could also increase the populations of total thermophilic and mesophilic bacteria as well as PAH-degrading bacteria, but this pattern was restricted only to the early stage of the composting process. High amounts of pig manure in the composting mass reduced the seed germination or root growth of cress seeds, but the composting process was effective in reducing the phytotoxic effects of the compost. Amendment of pig manure was beneficial to PAH removal during composting treatment and maximum removal rate at the end of composting accounted for 90% of the initial concentrations of PAHs. A pig manure application rate of 25% showed the most efficient removal of 3-ringed PAHs (phenanthrene and anthracene), while no significant difference in pyrene removal for those receiving 25 or 50% pig manure amendment. Taking into consideration the effects of pig manure on seed germination and available nutrients in the composting mass, this study suggested that a pig manure amendment of 25%, i.e., 3:1 ratio of contaminated soil: pig manure, is recommended to co-compost with PAH-contaminated soil.

A three-factor model of trait anger: dimensions of affect, behavior, and cognition.

The structure of trait anger was tested in a study of 24 self-report scales. Exploratory factor analyses in an undergraduate sample (N = 457) yielded a two-factor model (comprising cynicism and aggression) and a three-factor model (representing angry emotions, aggressive behaviors, and cynicism). Subsequent evaluations, including confirmatory factor analyses, indicated that the three-factor model provided the best characterization of the trait anger domain. The three-factor solution was consistent with an "ABC" conceptualization of trait anger, consisting of the dimensions of affect, behavior, and cognition. The three factors showed strikingly different associations with the Big Five personality traits. Angry Affect was most strongly related to Neuroticism, whereas Behavioral Aggression was associated with low Agreeableness. Cynical Cognition represented a blend of neurotic and disagreeable characteristics. Modest mean-level differences were observed between the genders for each factor.

Increased responses of glucagon and glucose production to hypoglycemia with intraperitoneal versus subcutaneous insulin treatment.

The study aim was to investigate the effect of the route of insulin treatment on the glucagon and glucose production (GP) responses to hypoglycemia in the diabetic rat. Experiments were performed in 4 groups of rats: (1) streptozotocin (STZ)-induced diabetic, untreated (D, n = 7), (2) diabetic treated with subcutaneous insulin (DSC, n = 8), (3) diabetic treated with intraperitoneal insulin (DIP, n = 6), and (4) normal control (N, n = 10). Slow-release insulin implants were used in DSC and DIP rats for 10 to 14 days (3 U/d). A hyperinsulinemic (120 pmol x kg(-1) x min(-1) insulin)-hypoglycemic (glycemia = 2.5 +/- 0.1 mmol/L) clamp following an isoglycemic basal period was performed in 5-hour fasted rats. Basal plasma glucose was normalized in both DSC and DIP rats; however, in DSC but not DIP rats, glucose normalization required peripheral hyperinsulinemia. Tracer-determined GP, which was elevated in D rats, was completely normalized in DIP but only partially corrected in DSC rats. Basal glucagon levels were similar in all groups. During hypoglycemia, GP was suppressed in D rats (delta, -28.9 +/- 5.0 micromol x kg(-1) x min(-1), moderately increased in DSC rats (delta, 6.1 +/- 5.6, P < .01 v D), but markedly increased in DIP and N rats (delta, 34.5 +/- 4.5 for DIP and 16.8 +/- 2.8 for N; P < .01 vD, P < .05 for DIP v DSC or N). Plasma glucagon increased 6-fold in N (945 +/- 129 pg/mL), only doubled in D (424 +/- 54), and tripled in DSC (588 +/- 83), but increased 5-fold in DIP rats (1,031 +/- 75, P < .05 v D and DSC). We conclude that in STZ-diabetic rats, (1) intraperitoneal but not subcutaneous insulin treatment normalizes basal GP, and (2) intraperitoneal insulin treatment as compared with subcutaneous treatment alleviates peripheral hyperinsulinemia and results in increased glucagon and GP responses to hypoglycemia.

The contraceptive self-efficacy scale: analysis in four samples.

Previous research has established a relationship between contraceptive self-efficacy (CSE), as measured by the 18-item CSE scale, and young women's contraceptive behavior. In this paper, the authors continue to explore the scale and its relationship to contraceptive behavior with four diverse samples to establish generalizability and to set guidelines for use of the scale. A series of correlational analyses were conducted with each sample. A pattern of low correlations among CSE items across samples emerged, indicating that use of the total item set separately as the basis for CSE was warranted. Zero-order and partial correlations revealed which CSE items were correlated with contraceptive behavior as well as which items explained unique variance in contraceptive behavior for each sample. Regression analyses showed that CSE was significantly predictive of contraceptive behavior for all samples. These results are discussed in terms of scale properties and use in research and clinical settings. Educational implications are formulated as well.

The short-term natural history of irritable bowel syndrome: a time-series analysis.

Although researchers have studied irritable bowel syndrome (IBS), including its physiological and psychological characteristics and treatments' effectiveness, basic descriptive information about IBS has been limited to lists of symptoms and explanations of what IBS is not. The purpose of the present study is to describe how core IBS symptoms vary over time. Twenty-five subjects (17 females, 8 males), who were not receiving treatment for IBS, rated the severity of their IBS symptoms daily for 8 weeks. Four symptoms' (abdominal pain, abdominal tenderness, constipation and diarrhea) ratings were slimmed to create a primary IBS symptom score. The data were detrended, then a time-series analysis was performed. Many subjects' IBS severity was predictable over more than one day, and symptoms tended to occur in clusters rather than randomly. Anxiety and depression were slightly to moderately correlated with IBS variables, but virtually all of these correlations were nonsignificant.

Gay men's safer sex behavior: an integration of three models.

This cross-sectional study explored gay men's sexual risk behavior from the perspective of three popular conceptual models, the health belief model, the theory of reasoned action, and social cognitive theory. Data were collected from sexually active gay men via anonymous questionnaire containing questions about sexual behavior and items related to the constructs comprising the three models. Using structural equation modeling techniques (LISREL 8), self-reported condom use was examined from the perspective of each theory. The results suggested that a substantial part of the variance in unprotected anal intercourse could be explained by conceptually analogous constructs common to these models. These constructs referred to the cognitive-affective reactions toward condoms and to the social context of using condoms. An additional variable unique to social cognitive theory, self-efficacy, added to the explained variance in the criterion above and beyond the variables that were common to the models. Relevant variables from the three theories were integrated into an expanded self-efficacy model.

The prediction of accurate contraceptive use from attitudes and knowledge.

A framework of the relationship between knowledge, attitudes, and behavior was described in the context of couple's use of birth control. It was hypothesized that when knowledge of behavioral enactment is present, attitudes and beliefs about susceptibility to pregnancy will be predictive of accurate use of the diaphragm. Respondents were 111 women who participated in a three-wave panel design focusing on diaphragm use. Analyses indicated that the level of knowledge about what a woman should do to use the diaphragm correctly was high. Correct knowledge, however, did not translate into accurate behavior. Motivational factors focusing on attitudes, perceived susceptibility to pregnancy, and normative factors were also relevant.

PIP: This study sought to predict and understand the behavioral criterion for accurate contraceptive usage using knowledge and attitudinal variables as major predictors. Building on the research of Fishbein into the prediction of aggregated behaviors over time (multiple act criteria), accurate use of contraception is conceptualized as an aggregation of many acts over time. Fishbein's framework is also extended to include the variables of perceived susceptibility to pregnancy and the influence of the male partner's attitude toward contraception. The subjects of the study were 111 family planning (FP) clients who identified the diaphragm as their major contraceptive during the eight-month test period. The sample was approximately divided between new users, restarters, and continuing users. Two follow-up interviews were used to measure accuracy of use, attitude toward method, attitude toward becoming pregnant, perceived susceptibility to pregnancy, partner attitude, and knowledge. Analyses were performed to detect the presence of selection, retention, and testing biases (nothing of significance was found). It was found that the women had high and persistent knowledge about proper use of a diaphragm. This knowledge did not ensure accurate behavior, however. Women were influenced by motivational factors such as relative contraceptive utility (attitude toward the diaphragm and toward becoming pregnant), perceived pregnancy susceptibility, and perceived partner attitude. This latter affected accuracy through its intermediate effects on relative contraceptive utility. Inaccurate use was most often associated with failure to check for holes and failure to apply additional spermicide if intercourse was repeated. These behavioral failures are less likely to result in contraceptive failure than other factors for which high accuracy was observed (length of time inserted or use of spermicide). These findings suggest that motivational and knowledge factors play a role in ensuring correct contraceptive usage and should receive the attention of FP counselors.

Relationship of trait anger to resting blood pressure: a meta-analysis.

A series of meta-analyses were conducted to assess whether anger is related to essential hypertension. The present review also considered the relevance of the distinction between anger experience and anger expression, the effect of participant selection bias, and the white-coat hypertension effect for the anger-blood pressure (BP) association. Anger experience was correlated with elevated BP, but the relationship was small and highly variable. When positive effects emerged, both participant selection and the reliability of BP measurement posed interpretational problems. Persons high in anger are not merely exhibiting elevated BP in response to testing, so a white-coat effect is not evident. Being labeled as hypertensive may contribute to higher anger scores, however. The review suggests lines of future research concerning associations between trait anger and blood pressure.

A multilevel data-analytic approach for evaluation of relationships between daily life stressors and symptomatology: patients with irritable bowel syndrome.

Four statistical strategies were used to evaluate whether occurrence of daily stressors increases lower gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) patients. Across-subject concurrent correlations between weekly stress and symptoms were positive but casually ambiguous and obscured between- and within-subject and occasion relationships. Multiple regressions assessing (weekly and daily) relations showed that prior symptoms predicted subsequent symptoms but that prior and concurrent daily stress had no consistent effects. Idiographic correlations also showed little evidence for a relationship between stress and symptoms. Daily stress did not appear to increase GI symptoms in IBS patients on a general basis. Daily recording methodology, in conjunction with within-subject analytic strategies, is proposed as an innovative approach to examine relations between stress and physical symptomatology.

Long-term monitoring of psychosocial stress and symptomatology in inflammatory bowel disease.

Eleven subjects with inflammatory bowel disease (IBD) participated in a longterm self-monitoring investigation of the relationship between psychosocial stress and IBD symptomatology. Two measurement instruments, the IBD Symptom Diary and the Psychosocial Stress Diary, were completed by each subject for 7 consecutive days each month for one year. Pooled time-series analysis of the influence of daily stress on IBD activity revealed a significant effect. A positive concurrent relationship was found between both daily and monthly psychosocial stress and IBD activity. Investigations of temporal relationship among variables revealed a negative effect of previous month stress on IBD. Results suggest a monthly rebound effect whereby IBD symptom severity is negatively responsive to the severity of the previous month stress. The effects of stress upon IBD were not found to be modified by behavioral coping strategies. These results support the prevailing impression that psychosocial stress contributes to the clinical course of IBD, and specifically suggest an influential role of daily and monthly stress. A pattern matching IBD's characteristic waxing and waning clinical course emerges when the association between stress and IBD is examined from a monthly viewpoint. Refinement of our knowledge of the IBD-stress model calls for replication and explanation of the monthly rebound effect as well as investigations into type of stressor and coping strategy that may influence IBD activity.

The relationship between trait hostility and cardiovascular reactivity: a quantitative review and analysis.

Results of a series of meta-analyses indicated that high and low scorers on most trait hostility measures do not consistently differ in blood pressure or heart rate reactivity to traditional laboratory stressors. The few significant effects were modest in size, and instances of hyporeactivity were found. When stressors were classified as provocative versus nonprovocative, in accord with Trait x Situation approaches, however, Potential for Hostility-Interpersonal Style was predictive of exaggerated systolic and diastolic blood pressure responses and the Cook-Medley Hostility Inventory was predictive of diastolic blood pressure responses to provocative stressors. Hence, the next generation of studies of the hostility-reactivity hypothesis should emphasize interpersonal stressors. Alternative mechanisms for the disease consequences of hostility should also be examined, however, because the available evidence indicates that the hyperreactivity hypothesis is unlikely to furnish a complete explanation for the association between hostility and heart disease.

Condom use: a self-efficacy model.

A survey of heterosexually active college students gathered information about condom use, self-efficacy (SE), outcome expectancies, sexual attitudes, peer group influences, acquired immunodeficiency syndrome (AIDS) knowledge, and perceived vulnerability to AIDS. On the basis of A. Bandura's (1986) social-cognitive theory, a structural model with SE as the central mediator was formulated and evaluated with LISREL. This model explained 46% of the variance in condom use from judgments of SE and effects attributable to peers and 53% of the variance in SE from outcome expectancies and peer group influences. Sexual attitudes, AIDS knowledge, and perceived vulnerability did not predict condom use. Most students were well-informed about human immunodeficiency virus (HIV) transmission but reported not feeling at risk, even though many engaged in risky sexual behavior.

PIP: Psychological factors, associated, with sexual risk behavior were investigated guided by A. Bandura's (1986) social-cognitive theory. It was examined whether a self-efficacy (SE) model is capable of predicting condom use from expectancies, social influences, peer group comparison, sexual attitudes, perceived risk for HIV infection, and AIDS-related knowledge. A self-report questionnaire was developed to gather information. A final sample of 212 single heterosexual and currently sexually active undergraduate students (103 men and 109 women) completed an anonymous survey. The ethnic composition was 83% Caucasian, 8% African-American, 3% Hispanic and 6% other. The state religious affiliation was 28% Catholic, 37% Jewish. 24% Protestant, and 11% other. The mean age of the respondents was 21.4 years (men = 21.8 years; women = 21.1 years). The subjects reported a mean number of 1.8 sex partners during the past 6 months and a mean number of 5.4 sex partners during the past 3 years. Only 29% of the subjects reported consistently having condoms during the past 6 months. 73% claimed pregnancy prevention and only 17% mentioned fear of AIDS. 80% of the students perceived themselves only slightly at risk for HIV infection. The fit of the model was evaluated with LISREL VII. The variables in the model accounted for 46% of the measurement error variance in condom use and for 53% of the variance in SE. Consistent with social-cognitive theory, condom use was predicted by SE beliefs, but it was also significantly predicted by peer group comparison. SE was predicted by self-comparisons with one's peer group and by outcome expectancies: positive expectancies about condom use (disease and pregnancy prevention) were directly related to Se, whereas negative expectancies (reduction of pleasure) were inversely associated with SE. Consistent with predictions, AIDS knowledge was unrelated to condom use. A positive correlation between AIDS knowledge scores and perceived vulnerability to HIV infection was found, but perceived vulnerability was not a significant predictor of either SE or condom use.

Multiple role juggling and daily mood states in working mothers: an experience sampling study.

The effects of multiple role juggling (i.e., simultaneously attending to demands of different roles) on daily mood states of employed mothers were examined. Ss completed activity and mood questionnaires 8 times a day for 8 days. Multiple role juggling had immediate negative effects on task enjoyment and mood. However, contrast effects and habituation to role juggling occurred when mood and satisfaction were examined over time. Furthermore, mood states tended to spill over from one episode to the next within a day, but contrast effects were found across days. These results reflect the complex nature of psychological adjustment to multiple role occupancy.

The Detection and Interpretation of Interaction Effects Between Continuous Variables in Multiple Regression.

issues in the detection and interpretation of interaction effects between quantitative variables in multiple regression analysis are discussed. Recent articles by Cronbach (1987) and Dunlap and Kemery (1987) suggested the use of two transformations to reduce "problems" of multicollinearity. These transformations are discussed in the context of the conditional nature of multiple regression with product terms. It is argued that although additive transformations do not affect the overall test of statistical interaction, they do affect the interpretational value of regression coefficients. Factors other than multicollinearity that may account for failures to observe interaction effects are noted.

The relation between type A behavior and chronic emotional distress: a meta-analysis.

A meta-analysis was conducted of studies examining the relation between Type A behavior and chronic emotional distress as measured by standard psychological scales. Aggregating across all studies, the average effect size was .27, indicating a positive association between Type A and chronic dysphoria; however, there was considerable variability in the size of the relation among studies. Partitioning by Type A measure revealed that Structured Interview-assessed Type A was unrelated to chronic dysphoric emotions; however, most of the self-report measures of Type A behavior were moderately correlated with upset. The Framingham Type A Scale and the Bortner Scale showed the strongest relations. Thus, contrary to the traditional view, Type A measured by self-report does have some emotional concomitants, although they are not in the pathological range. Also discussed are how the results bear on the proposal that the maladjusted personality confers coronary risk, the implications for reported associations between Type A and illness complaints, and for the study of the Type A as a social psychological construct.

Effects of sensory and procedural information on coping with stressful medical procedures and pain: a meta-analysis.

A meta-analysis of studies on preparation for medical procedures and pain evaluated the relative effects of sensory; procedural, and combined sensory-procedural preoperational information on coping outcomes. Results indicated that, in contrast to sensory information, procedural information provided no significant benefits over control group instruction. Combined sensory-procedural preparation, however, yielded the strongest and most consistent benefits in terms of reducing negative affect, pain reports, and other-rated distress. The meta-analytic results are consistent with the dual process preparation hypothesis, which proposes that the information combination is optimal because procedural details provide a map of specific events while sensory information facilitates their interpretation as nonthreatening. It is concluded that a combined preparation is the preferred clinical option.

In search of the false-uniqueness phenomenon: fear and estimates of social consensus.

An examination of the social perception literature yields little evidence for the false-uniqueness phenomenon (Valins & Nisbett, 1972), the perception that one's attributes are more unique than is the case. In contrast, the tendency for individuals to project their own characteristics onto other people and assume that more people are like themselves is a robust phenomenon. One reason researchers may not have found false uniqueness is that they have not looked at the accuracy of consensus estimates. A close look at the results of Tabachnik, Crocker, and Alloy (1983) and Sanders and Mullen (1983), who did assess accuracy, suggests that people possessing undesirable attributes over-estimate consensus, whereas people holding desirable attributes underestimate consensus. The latter pattern is a form of false uniqueness. In this study we looked at the accuracy of social consensus estimates in the context of psychological fears. A sample of subjects filled out an abbreviated version of a fear survey and made estimates of consensus. The results showed that both high- and low-fear respondents overestimated the incidence of high fear among their peers, but high-fear subjects were more inaccurate in their estimates. A false-uniqueness effect was found on the part of low-fear subjects, as they tended to underestimate the incidence of low fear among their peers. These findings are consistent with a motivational interpretation that emphasizes the individual's need to justify or normalize stigmatized behavior and to bolster perceived self-competence.