Topical ibuprofen inhibits blushing during embarrassment and facial flushing during aerobic exercise in people with a fear of blushing

The flush that develops during whole-body heat stress depends partly on prostaglandins production in the skin. Variations in the strength of this local mechanism may contribute to individual differences in susceptibility to blushing and associated anxiety. To investigate this in the present study, the anti-inflammatory agent ibuprofen (which blocks prostaglandins formation) was applied topically to a small area of the cheek in 16 participants with a fear of blushing and in another 14 without this fear. Changes in skin blood flow were monitored at the ibuprofen-treated site and at a mirror image control site while participants sang (to induce embarrassment and blushing) and during aerobic exercise (to induce flushing). The topical ibuprofen treatment inhibited increases in cheek blood flow in both groups during both of these tasks. However, increases in cheek blood flow were greater in participants with high than low fear of blushing immediately after exercise. These findings suggest that prostaglandins contribute to dilatation of facial blood vessels both during emotional arousal (embarrassment) and aerobic exercise. Furthermore, fear of blushing may be associated with mechanisms that delay the resumption of normal vascular tone after a period of vasodilatation. Whether topical ibuprofen gel is suitable for intermittent or long-term use as an aid for blushing control requires further investigation.     

Histamine H1- and H2-receptors in the gastric vasculature of the rabbit

The histamine receptors in the rabbit blood perfused gastric vasculature were analysed pharmacologically. Histamine elicited a monophasic increase in perfusion pressure which was antagonized by mepyramine and enhanced by metiamide. The maximum observed response was enhanced by metiamide to that produce by a specific H₁-receptor agonist. It is concluded that the gastric vasculature responds to histamine with an H₁-receptor mediated vasoconstriction and an H₂-receptor mediated dilation. In this preparation the H₁-effect predominates in response to injection of histamine.     

Daily marijuana use and suicidality: the unique impact of social anxiety

Despite a clear relationship between marijuana use and suicidality, little is known about psychological vulnerability factors that may interact with marijuana use to increase suicidality among this high-risk group. The present study examined the moderational impact of social anxiety on the relationship between marijuana use status (current users vs abstainers) and suicidality among 343 community adults. We also examined whether social anxiety moderated the relation between more frequent use (daily vs less frequent) among the 134 current marijuana users. Although social anxiety did not moderate the relation between use status and suicidality, it did moderate the relation between daily use status and suicidality after controlling for a wide range of relevant variables (e.g., demographics, depression, negative affect, and other types of anxiety). The overall model accounted for 59% of the variance in suicidality such that daily marijuana users with elevated social anxiety reported the highest suicidality. Findings highlight the importance of considering social anxiety in efforts to understand and prevent suicidality among this high-risk population.     

帕罗西汀治疗伴情绪障碍的偏头痛

目的：探讨帕罗西汀治疗伴有情绪障碍的偏头痛的临床疗效。方法：将偏头痛病人127例分为2组,帕罗西汀组68例[男性26例,女性42例,年龄(30±s 12)a,13～74 a],口服帕罗西汀20 mg,每早1次,1 wk后加至40 mg,每早1次,头痛缓解1wk后给予维持量10mg,每早1次；硫必利组59例[男性24例,女性35例,年龄(30±18)a,15～68 a],入院后即给予硫必利100mg,每日3次,维持量为50 mg,每日2～3次,均6wk为一个疗程。进行对照研究,用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)对其抑郁焦虑状态进行治疗前及治疗后(wk 2,4,6)评估。结果：帕罗西汀组和硫必利组不仅可以明显减轻病人的抑郁焦虑症状,还可以显著减轻偏头痛发作次数,缩短头痛发作的时间(P＜0．01)；帕罗西汀组总有效率96%(65/68),硫必利组总有效率81%(48/59),2组疗效比较,经Ridit分析有显著差异(P＜0．05)。结论：帕罗西汀治疗伴有情绪障碍的偏头痛有较好疗效。     

Structure-activity relationship of analogues of endothelin-1: dissociation of hypotensive and pressor actions

The structural requirements of endothelin-1 to evoke depressor and pressor responses were studied in conscious rats. Formylation of the C-terminal Trp eliminated the depressor but not the pressor activity of endothelin-1. Oxidation of Met⁷ in this analogue restored the hypotensive activity. Destruction of the Cys¹-Cys¹⁵ disulphide bridge led to a weak agonist with both depressor and pressor activities. Formylalion of Trp²¹ in this analogue resulted in a complete loss of biological activity. These results indicate that Met⁷ and the indole moiety of Trp²¹ are important for the expression of the depressor activity of endothelin-1 whereas the intramolecular loop structure is less important. The results also provide further evidence that the depressor and pressor effects of endothelin-1 are mediated through different receptors.     

Histamine augments beta2-adrenoceptor-induced cyclic AMP accumulation in human prostate cancer cells DU-145 independently of known histamine receptors

Androgen-independent prostate cancer cells DU-145 express a number of G protein-coupled receptors, including histamine H1 receptors. There is evidence for the presence of beta-adrenoceptors in the human prostate, and in this work we set out to characterise the expression of beta-adrenoceptors by DU-145 cells, their linking to cyclic AMP (cAMP) formation and the possible modulation by histamine H1 receptors of beta-adrenoceptor function. Saturation [3H]-dihydroalprenolol binding indicated that DU-145 cells express moderate levels of beta-adrenoceptors (22.7+/-2.5 fmol/mg protein), which belong to the beta2-subtype as assessed by inhibition by the antagonists ICI-118,551 and CGP-20712A. Inhibition of [3H]-dihydroalprenolol binding by agonists (noradrenaline, adrenaline and isoproterenol) showed the presence of both high-(53-59%) and low-affinity binding sites. beta-Adrenoceptor stimulation with isoproterenol resulted in robust [3H]-cAMP accumulation (10-30-fold of basal, EC50 142 nM; pEC50 6.85+/-0.05). While not having effect of its own on basal [3H]-cAMP accumulation, histamine significantly augmented the beta2-adrenoceptor-induced response (overall effect 152+/-6% of isoproterenol alone) with EC50 1.35 microM (pEC50 5.87+/-0.06). This effect was independent of extracellular Ca2+, insensitive to antagonists/agonists at H1, H2 or H3/H4 receptors and mimicked by drugs containing an imidazole ring in their chemical structure and by imidazole itself. Taken together, our results show that in DU-145 cells histamine augments beta2-adrenoceptor-induced cAMP independently of the activation of known histamine receptors. The effect may involve other mechanisms such as allosteric modulation of beta2-adrenoceptors by the imidazole moiety of histamine.     

Clarifying the Relation between Social Interaction Anxiety and Cannabis Use: Personality as a Distinguishing Factor

Background: Individuals with social interaction anxiety, a facet of social anxiety disorder, are heterogeneous with respect to approaching or avoiding risky behaviors, including substance use. Additionally, the relation between social anxiety and cannabis use frequency has been inconsistent in the literature. Objective: The present study aimed to clarify the relation between social interaction anxiety and cannabis use by examining the effects of personality traits known to differentially predict substance use, including sensation seeking, emotion dysregulation, urgency, behavioral approach, and behavioral inhibition. Methods: We explored heterogeneity in social interaction anxiety using finite mixture modeling to discern profiles differing in mean scores on measures of social interaction anxiety and personality. We then examined how profiles differed in their likelihood of cannabis use. Results: The profile with low social interaction anxiety and high scores on personality measures was the most likely to use cannabis at all time periods. Two profiles with high social interaction anxiety scores were discerned. Between these two profiles, the profile with the highest levels of social interaction anxiety and most measured personality traits was more likely to use cannabis across all measured time periods. The profile with the high social interaction anxiety and low scores on personality measures was the least likely to use cannabis. Conclusions: Results of the present study identified personality traits most associated with increased risk of cannabis use for people high and low in social interaction anxiety, including facets of emotion regulation, urgency, and sensation seeking.     

Social impressions while drinking account for the relationship between alcohol-related problems and social anxiety

Individuals with elevated social anxiety appear particularly vulnerable to experiencing alcohol-related problems; yet we know little about factors that may account for this relationship. One possibility is that socially anxious individuals hold beliefs about the impressions they make on others while drinking and these beliefs play an important role in their drinking behaviors. The present study used exploratory factor analysis among participants with clinically elevated social anxiety (n=166) to develop a measure, the Social Impressions while Drinking Scale (SIDS), to assess beliefs regarding others' impressions of drinking behaviors that may be particularly relevant to socially anxious individuals. A valuations scale was also developed to assess the importance of each belief. Empirically-derived subscales were identified with adequate reliability. Among socially anxious participants, the Gregarious and Sexual Facilitation subscales were uniquely related to drinking problems and frequency respectively. Individuals with clinically meaningful social anxiety achieved higher scores on all SIDS subscales compared to those with lower social anxiety (n=166). Several SIDS scales mediated the relations between social anxiety group status and drinking problems (Interaction Fears, Observation Fears, Aggression, Gregariousness). Results highlight the importance of examining beliefs specific to high-risk populations in assessing their alcohol-related behaviors.     

Marijuana effect expectancies: relations to social anxiety and marijuana use problems

High social anxiety is related to marijuana problems, yet the nature of this relation remains unclear. We examined relations between marijuana effect expectancies, social anxiety, and marijuana among undergraduates (N=337). Social anxiety was related positively to Negative Expectancies and negatively to Tension Reduction Expectancies. Among socially anxious individuals, greater belief that marijuana produces Cognitive and Behavioral Impairment was associated with greater marijuana use rates. Negative Expectancies mediated the social anxiety-marijuana problems link. These data provide new insight into problematic marijuana use among this high-risk group.     

Examining the interrelationships between social anxiety, smoking to cope, and cigarette craving

Smokers with symptoms of social anxiety often report smoking as a way to cope with negative affect. These individuals have lower success rates when attempting cessation compared with the general population. However, there is a paucity of research examining the role of social anxiety in nicotine dependence. The present study explored the relationships between symptoms of social anxiety, smoking to cope with these symptoms during social situations (STC), and cigarette craving. Thirty-eight participants completed measures of social anxiety and STC at baseline. Cigarette craving was subsequently assessed pre and post exposure to smoking-related images during periods of nicotine satiation and deprivation. Regression analyses revealed that greater symptoms of social anxiety predicted the frequency of STC behaviors and the number of cigarettes participants thought they would need in order to feel more comfortable in social situations. Symptoms of social anxiety and several behaviors associated with STC (e.g., avoiding social situations in which smoking is not permitted) predicted increases in craving during nicotine deprivation, but not satiation. These findings suggest that symptoms of social anxiety and STC behaviors may play a role in the maintenance of smoking behaviors. Further, targeting symptoms of social anxiety within the context of smoking cessation treatment may be particularly helpful and may improve the rates of smoking cessation among individuals with symptoms of social anxiety.     

Effects of impromidine- and arpromidine-derived guanidines on recombinant human and guinea pig histamine H1 and H2 receptors

Imidazolylpropylguanidines derived from impromidine and arpromidine are more potent and efficacious agonists at the guinea pig histamine H2 receptor (gpH2R) than at the human H2R (hH2R) in the GTPase assay. Additionally, such guanidines are histamine H1 receptor (H1R) antagonists with preference for the human relative to the guinea pig receptor. The purpose of this study was to examine structure-activity relationships of guanidines at human and guinea pig H1R and H2R species isoforms expressed in Sf9 insect cells. Three impromidine analogues and six arpromidine analogues exhibited agonistic activity at H2R and antagonistic activity at H1R as assessed in the steady-state GTPase assay. Species selectivity of derivatives was similar as compared with the parent compounds. None of the structural modifications examined (different aromatic ring systems and different ring substituents) was superior in terms of H2R potency and efficacy relative to impromidine and arpromidine, respectively. These data point to substantial structural constraints at the agonist binding site of H2R. Guanidines exhibited distinct structure-activity relationships for H1R antagonism in a radioligand competition binding assay and the GTPase assay and for H1R inverse agonism. Our data indicate that it is difficult to obtain guanidine-type agonists with high potency and high efficacy for hH2R, but those compounds may be useful tools for exploring the antagonist binding site and constitutive activity of H1R.     

Enhanced antinociception by intrathecally-administered morphine in histamine H1 receptor gene knockout mice

We previously reported that histamine H₁ receptor gene knockout mice (H1KO) showed lower spontaneous nociceptive threshold to pain stimuli when compared to wild-type mice. The objective of the present study was to examine the antinociceptive effect of intrathecally-administered morphine in H1KO mice. The antinociceptive effects of morphine were examined using assays for thermal (tail-flick, hot-plate, paw-withdrawal), mechanical (tail-pressure) and chemical nociception (formalin and capsaicin tests) using H1KO and wild-type mice. In these nociceptive assays, intrathecally-administered morphine produced significant antinociceptive effects in wild-type mice. The antinociceptive effect produced by intrathecally administered morphine was enhanced in the knockout mice. We also examined the effect of an histamine H₁ receptor antagonist, an active (d-) isomer of chlorpheniramine, on morphine-induced antinociception in ICR mice. The intrathecal co-administration of d-chlorpheniramine enhanced the effect of morphine in all nociceptive assays examined. The pharmacological experiments using d-chlorpheniramine further substantiate the evidence for the histamine H₁ receptor-mediated suppression of morphine-induced antinociception. These results suggest that existing H₁ receptors play an inhibitory role in morphine-induced antinociception at the spinal cord level.     

胎儿铅暴露对婴儿情绪发育的影响

目的研究宫内铅暴露对日后婴幼儿情绪发育的影响,探讨导致婴儿情绪障碍的原因。方法选取足月新生儿脐带血测量血铅,并按照脐血铅含量分3组,A组为血铅0￣200μg/L,B组为血铅￣500μg/L,C组为血铅>500μg/L。追踪观察这3组新生儿9个月时的情绪发育情况,同时做关于情绪和社会适应能力(ASQ)的问卷调查,比较不同脐血铅对婴幼儿情绪发育的影响。结果3组间的ASQ分值差异有统计学意义(P<0.01),且随着血铅值的升高,ASQ分值也越高(分值和情绪发育呈负相关)。结论胎儿铅暴露在一定程度上可以造成日后婴幼儿情绪发育和社会适应能力的异常。     

Understanding the relationship between social anxiety and alcohol use in college students: A meta-analysis

Many college students use alcohol, and most of these students experience problems related to their use. Emerging research indicates that socially anxious students face heightened risk of experiencing alcohol-related problems, although the extant research on alcohol use and social anxiety in this population has yielded inconsistent findings. This meta-analysis was conducted to examine the relationship between social anxiety and alcohol variables in college students. A literature search was used to identify studies on college students that included measures of social anxiety and at least one of the alcohol variables of interest. All analyses were conducted using random effects models. We found that social anxiety was negatively correlated with alcohol use variables (e.g., typical quantity and typical frequency), but significantly positively correlated with alcohol-related problems, coping, conformity, and social motives for alcohol use, and positive and negative alcohol outcome expectancies. Several moderators of effect sizes were found to be significant, including methodological factors such as sample ascertainment approach. Given that social anxiety was negatively related to alcohol use but positively related to alcohol-related problems, research is needed to address why individuals high in social anxiety experience more problems as a result of their alcohol use. Avoidance of social situations among socially anxious students should also be taken into account when measuring alcohol use. The primary limitation of this study is the small number of studies available for inclusion in some of the analyses.     

No evidence for central histamine-receptor involvement with the hypotensive effect of clonidine in cats

In conscious hypertensive cats, intraventricular (i.c.v.) administration of clonidine (25 μg), induced hypotension and bradycardia. Pretreatment with metiamide (2 mg i.c.v.) did not significantly antagonise either the hypotension or bradycardia induced by clonidine (25 μg), but induced marked behavioural changes. Central pretreatment with mepyramine (200 μg, i.c.v.) or procaine (600 μg i.c.v.), reduced the hypotension evoked by clonidine (25 μg), but no antagonism of the clonidine-induced bradycardia was apparent. Central phentolamine (200 μg, i.c.v.) or tolazoline (200 μg, i.c.v.) antagonised the hypotension and bradycardia evoked by i.c.v. clonidine.     

H1-histaminergic activation stimulates phosphatidylinositol labeling in rabbit aorta

Histamine and 2-(2-aminoethyl)-thiazole induced dose-dependent increases in the labeling of phosphatidylinositol in rabbit aorta whereas impromidine was without effect. The effect of histamine was inhibited by antihistamines with the following order of potency: mepyramine pyrilamine cimetidine. The data indicate that H₁-histaminergic activation stimulates phosphatidylinositol labeling in rabbit aorta and suggest the involvement of a calcium-signaling process in the action of H₁-histaminergic receptors.     

Cannabis-related impairment and social anxiety: the roles of gender and cannabis use motives

Social anxiety appears to be especially related to cannabis-related problems, yet the nature of this association remains unclear. Some data suggest that socially anxious men may be especially vulnerable to problematic cannabis use. The current study examined the relations between social anxiety, cannabis use and use-related problems, and motives for cannabis use by gender among 174 (42.5% female) current (past-month) cannabis users. Among men, social anxiety was significantly, positively related to the number of cannabis-related problems and coping and conformity motives. Coping and conformity motives mediated the relation between social anxiety and cannabis-related problems. Among women, social anxiety was significantly related only to social motives, and was unrelated to cannabis-related problems. These findings suggest that socially anxious men may be especially vulnerable to using cannabis as a means of avoidance coping (avoiding scrutiny and negative affect), which may contribute to the high rates of cannabis-related problems among socially anxious individuals.     

Severity of anxiety in mental health versus addiction treatment settings when social anxiety and substance abuse are comorbid

There is increasing interest in the co-occurrence of social anxiety and addiction. Each investigation has a specific vantage point, e.g. the effect social anxiety has in a population with addiction or that of addiction in a population with social anxiety, which could create unique findings. Among comorbid individuals, is social anxiety more severe in people seeking treatment for anxiety, as compared to those seeking treatment for addiction? This report compares social anxiety severity between subjects in two studies—one involving socially anxious individuals (n = 38) seeking treatment for addictions; the other (n = 41) subjects with social anxiety and an alcohol use disorder, seeking treatment for social anxiety. Baseline severity scores on the Liebowitz Social Anxiety Scale for social anxiety were compared between the groups. No significant differences were found. For both groups, social anxiety was largely in the severe range. The results suggest that clinicians should attend to social anxiety symptom severity in patients with co-occurring social anxiety and addiction, regardless of the condition for which treatment is sought.     

Smoking and social anxiety: The roles of gender and smoking motives

Although social anxiety appears to be a risk factor for smoking and nicotine dependence, little work has identified factors that may play a role in these relationships. The current study examined the role of gender and smoking motives in these relationships among 945 (73.0% female) undergraduates, 91 of whom were current daily smokers. Among women, social anxiety was related to daily smoking status, whereas it was related to dependence severity among men. After controlling for past-week smoking frequency, social anxiety was related to affiliative attachment and behavioral choice-melioration smoking motives. Both motives mediated the relationship between social anxiety and nicotine dependence severity, although affiliative attachment motives uniquely mediated this relationship. Results suggest that socially anxious individuals who view cigarettes as having some of the same characteristics as social interactions may be particularly vulnerable to more severe nicotine dependence. Results also highlight the importance of considering gender in the relationships between social anxiety and smoking behaviors.     

Marijuana use motives and social anxiety among marijuana-using young adults

Given the high rates of co-occurring marijuana use and social anxiety, the present investigation examined the relations among marijuana use motives, marijuana use and problems, and social anxiety in 159 (54.7% female) young adults (M(age)=18.74, SD=1.20). As expected, after covarying for a number of variables related to both marijuana use and social anxiety (e.g. gender, alcohol use problems, anxiety sensitivity), social anxiety predicted greater numbers of marijuana use problems. Interestingly, social anxiety was not related to marijuana use frequency. Also consistent with prediction, social anxiety was a significant predictor of coping and conformity motives for marijuana use above and beyond relevant variables. Finally, coping motives for marijuana use mediated the relation between social anxiety and marijuana use problems. These data provide novel evidence for the unique effects of coping-motivated marijuana use in the link between marijuana-related impairment and social anxiety.