Cholesterol induced heart valve inflammation and injury: efficacy of cholesterol lowering treatment.

BACKGROUND: Heart valves often undergo a degenerative process leading to mechanical dysfunction that requires valve replacement. This process has been compared with atherosclerosis because of shared pathology and risk factors. In this study, we aimed to elucidate the role of inflammation triggered by cholesterol infiltration and cholesterol crystals formation causing mechanical and biochemical injury in heart valves. METHODS: Human and atherosclerotic rabbit heart valves were evaluated. New Zealand White male rabbits were fed an enriched cholesterol diet alone or with simvastatin and ezetimibe simultaneous or after 6 months of initiating cholesterol diet. Inflammation was measured using C-reactive protein (CRP) and RAM 11 of tissue macrophage content. Cholesterol crystal presence and content in valves was evaluated using scanning electron microscopy. RESULTS: Cholesterol diet alone induced cholesterol infiltration of valves with associated increased inflammation. Tissue cholesterol, CRP levels and RAM 11 were significantly lower in simvastatin and ezetimibe rabbit groups compared with cholesterol diet alone. However, the treatment was effective only when initiated with a cholesterol diet but not after lipid infiltration in valves. Aortic valve cholesterol content was significantly greater than all other cardiac valves. Extensive amounts of cholesterol crystals were noted in rabbit valves on cholesterol diet and in diseased human valves. CONCLUSIONS: Prevention of valve infiltration with cholesterol and reduced inflammation by simvastatin and ezetimibe was effective only when given during the initiation of high cholesterol diet but was not effective when given following infiltration of cholesterol into the valve matrix.

Duration of oral contraceptive use predicts women's initial and subsequent subjective responses to sexual stimuli.

Recent work suggests that a woman's hormonal state when first exposed to visual sexual stimuli (VSS) modulates her initial and subsequent responses to VSS. The present study investigated whether women's initial hormonal state was related to their subjective ratings of VSS, and whether this relationship differed with VSS content. We reanalyzed previously collected data from 14 naturally cycling (NC) women and 14 women taking oral contraceptives (OCs), who subjectively rated VSS at three hormonal time-points. NC women's ratings of 216 unique sexual images were collected during the menstrual, periovulatory, and luteal phases of their menstrual cycles, and OC women's ratings were collected at comparable time-points across their pill-cycles. NC women's initial hormonal state was not related to their ratings of VSS. OC women's initial hormonal state predicted their ratings of VSS with minimal contextual information and of images depicting female-to-male oral sex. Specifically, women who entered the study in the third week of their pill-cycle (OC-3 women) rated such images as less attractive at all testing sessions than did all other women. OC-3 women were also the only women to rate decontextualized VSS as unattractive at all testing sessions. These results corroborate previous studies in which women's initial hormonal state was found to predict subsequent interest in sexual stimuli. Future work, with larger samples, should more directly investigate whether OC-3 women's negative assessment of specific types of VSS reflects a reaction to the laboratory environment or a broader mechanism, wherein OC women's sexual interests decrease late in their pill-cycle.

Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women.

After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother-infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual desire was positively correlated with VTA activation to sexual images and with SES. Our findings show that postpartum decreases in sexual desire may in part be mediated by VTA activation, and oxytocin increased activation of the VTA but not NAc in response to sexual and infant stimuli. Oxytocin may contribute to the altered reproductive priorities in postpartum women by increasing VTA activation to salient infant stimuli.

Amygdala response to negative images in postpartum vs nulliparous women and intranasal oxytocin.

The neuroendocrine state of new mothers may alter their neural processing of stressors in the environment through modulatory actions of oxytocin on the limbic system. We predicted that amygdala sensitivity to negatively arousing stimuli would be suppressed in postpartum compared to nulliparous women and that this suppression would be modulated by administration of oxytocin nasal spray. We measured brain activation (fMRI) and subjective arousal in response to negatively arousing pictures in 29 postpartum and 30 nulliparous women who received either oxytocin nasal spray or placebo before scanning. Pre- and post-exposure urinary cortisol levels were also measured. Postpartum women (placebo) demonstrated lower right amygdala activation in response to negative images, lower cortisol and lower negative photo arousal ratings to nulliparous women. Nulliparous women receiving oxytocin had lower right amygdala activation compared to placebo. Cortisol levels in the placebo group, and ratings of arousal across all women, were positively associated with right amygdala activation. Together, these findings demonstrate reductions in both amygdala activation and subjective negative arousal in untreated postpartum vs nulliparous women, supporting the hypothesis of an attenuated neural response to arousing stimuli in postpartum women. A causal role of oxytocin and the timing of potential effects require future investigation.

Distribution of venous remodeling in exercise-induced pulmonary hemorrhage of horses follows reported blood flow distribution in the equine lung.

Exercise-induced pulmonary hemorrhage (EIPH), which has been reported in humans and a variety of domestic animals following strenuous exercise, is most often documented in racehorses. Remodeling of pulmonary veins (VR) in equine EIPH was recently described, suggesting that it contributes to the pathogenesis of the disease. The cause of VR is unknown. We tested the hypothesis that the development of VR follows pulmonary blood flow distribution, preferentially occurring in the caudodorsal lung region. Furthermore, we hypothesized that VR underpins development of the other lesions of EIPH pathology. The lungs of 10 EIPH-affected horses and 8 controls were randomly sampled for histopathology (2,520 samples) and blindly scored for presence and severity of VR, hemosiderin (H), and interstitial fibrosis (IF). Mean sample score (MSS), mean lesion score, and percent samples with lesions were determined in four dorsal and three ventral lung regions, and the frequency, spatial distribution, and severity of lesions were determined. MSS for VR and H were significantly greater dorsally than ventrally (P < 0.001) and also decreased significantly in the caudocranial direction (P < 0.001). IF decreased only in the caudocranial direction. The percent samples with lesions followed the same distribution as MSS. VR often was accompanied by H; IF never occurred without VR and H. Similarity of the distribution of EIPH lesions and the reported fractal distribution of pulmonary blood flow suggests that VR develops in regions of high blood flow. Further experiments are necessary to determine whether VR is central to the pathogenesis of EIPH.

Lower sexual interest in postpartum women: relationship to amygdala activation and intranasal oxytocin.

During the postpartum period, women experience significant changes in their neuroendocrine profiles and social behavior compared to before pregnancy. A common experience with motherhood is a decrease in sexual desire. Although the lifestyle and peripheral physiological changes associated with parturition might decrease a woman's sexual interest, we hypothesized that there are also hormone-mediated changes in women's neural response to sexual and infant stimuli with altered reproductive priorities. We predicted that amygdala activation to sexually arousing stimuli would be suppressed in postpartum versus nulliparous women, and altered with intranasal oxytocin administration. To test this, we measured amygdala activation using fMRI in response to sexually arousing pictures, infant pictures, and neutral pictures in 29 postpartum and 30 nulliparous women. Half of the women received a dose of exogenous oxytocin before scanning. As predicted, nulliparous women subjectively rated sexual pictures to be more arousing, and infant pictures to be less arousing, than did postpartum women. However, nulliparous women receiving the nasal oxytocin spray rated the infant photos as arousing as did postpartum women. Right amygdala activation was lower in postpartum versus nulliparous women in response to sexual, infant, and neutral images, suggesting a generalized decrease in right amygdala responsiveness to arousing images with parturition. There was no difference in right amygdala activation with nasal spray application. Postpartum women therefore appear to experience a decrease in sexual interest possibly as a feature of a more generalized decrease in amygdala responsiveness to arousing stimuli.

Influences of observer sex, facial masculinity, and gender role identification on first impressions of men's faces.

Evaluations of male faces depend on attributes of the observer and target and may influence future social and sexual decisions. However, it is unknown whether adherence to hypertraditional gender roles may shape women's evaluations of potential sexual partners or men's evaluations of potential competitors. Using a photo task, we tested participants' judgments of attractiveness, trustworthiness, aggressiveness, and masculinity of male faces altered to appear more masculine or feminine. Findings revealed that higher hypermasculinity scores in male observers were correlated with higher attractiveness and trustworthiness ratings of the male faces; conversely, higher hyperfemininity scores in female observers were associated with lower ratings on those traits. Male observers also rated the faces as more aggressive than did female observers. Regarding ratings by face type, masculinized faces were rated more aggressive than feminized faces, and women's ratings did not discriminate between altered faces better than men's ratings. These results suggest that first impressions of men can be explained in part by socioculturally- and evolutionarily-relevant factors such as the observer's sex and gender role adherence, as well as the target's facial masculinity.

Sexual desire, sexual arousal and hormonal differences in premenopausal US and Dutch women with and without low sexual desire.

The interaction between women's hormonal condition and subjective, physiological, and behavioral indices of desire or arousal remains only partially explored, in spite of frequent reports from women about problems with a lack of sexual desire. The present study recruited premenopausal women at two sites, one in the United States and the other in the Netherlands, and incorporated various measures of acute changes in sexual desire and arousal. A sample of 46 women who met criteria for Hypoactive Sexual Desire Disorder (HSDD) was compared to 47 women who experienced no sexual problems (SF). Half of each group used oral contraceptives (OCs). The specific goal was to investigate whether there is a relationship between women's hormone levels and their genital and subjective sexual responsiveness. Background demographics and health variables, including oral contraceptive (OC) use, were recorded and hormones (total testosterone (T), free testosterone (FT), SHBG, and estradiol) were analyzed along with vaginal pulse amplitude and self-report measures of desire and arousal in response to sexual fantasy, visual sexual stimuli, and photos of men's faces. Self-reported arousal and desire were lower in the HSDD than the SF group, but only for women who were not using oral contraceptives. Relationships between hormones and sexual function differed depending on whether a woman was HSDD or not. In line with prior literature, FT was positively associated with physiological and subjective sexual arousal in the SF group. The HSDD women demonstrated the opposite pattern, in that FT was negatively associated with subjective sexual responsiveness. The findings suggest a possible alternative relationship between hormones and sexual responsiveness in women with HSDD who have characteristics similar to those in the present study.

Incorporating emotions specific to the sexual response into theories of emotion using the Indiana Sexual and Affective Word Set.

The sexual response includes an emotional component, but it is not clear whether this component is specific to sex and whether it is best explained by dimensional or discrete emotion theories. To determine whether the emotional component of the sexual response is distinct from other emotions, participants (n = 1099) rated 1450 sexual and non-sexual words according to dimensional theories of emotion (using scales of valence, arousal, and dominance) and according to theories of basic emotion (using scales of happiness, anger, sadness, fear, and disgust). In addition, ratings were provided for newly developed scales of sexual valence, arousal, and energy. A factor analysis produced four factors, together accounting for 91.5% of the variance in participant ratings. Using logistic regression analysis, we found that one word category or factor, labeled "sexual," was predicted only by the new sexual arousal and energy scales. The remaining three factors, labeled "disgusting," "happy," and "basic aversive" were best predicted by basic (or discrete) emotion ratings. Dimensional ratings of valence, sexual valence, and arousal were not predictive of any of the four categories. These results suggest that the addition of sexually specific emotions to basic emotion theories is justified and needed to account fully for emotional responses to sexual stimuli. In addition, the findings provide initial validation for the Indiana Sexual and Affective Words Set (ISAWS), supporting its use in future studies.

Social segregation in male, but not female yearling rhesus macaques (Macaca mulatta).

Males and females of many species sex-segregate, ranging from complete separation of habitats to social segregation within the same space, sometimes varying across seasons and lifespan development. Mechanisms for such segregation are not well understood, though some have suggested that sex differences in preferred juvenile behaviors lead to greater behavioral compatibility within than between sexes. This within-sex behavioral compatibility may be the source of sex-segregation. As juvenile behavioral sex differences are well-documented in rhesus monkeys, we examined sex-segregation patterns of yearling rhesus monkeys engaged in three different types of behavior: rough play, parallel play, and grooming. We observed male and female rhesus yearlings from five stable long-term age-graded social groups of 67-183 animals. Behavioral observations were designed to collect equal numbers of rough play, grooming, and parallel play bouts. In addition, sex composition and proximity to adults was recorded for each bout. Across all behaviors, more all-male groups and fewer mixed sex-groups were observed than expected by chance. All-female groups occurred at the level expected by chance. Thus, males sex-segregated regardless of type of behavior, while females did not sex-segregate. Female groups were observed in proximity to adults more often than expected by chance. These results suggest that behavioral compatibility may produce sex-segregation in male yearling rhesus monkeys, possibly preparing males and females for different social roles and segregation as adults.

Women's interest in visual sexual stimuli varies with menstrual cycle phase at first exposure and predicts later interest.

This study investigated whether women's interest in visual sexual stimuli varied with their hormonal state. Viewing times of 30 women, 15 normal cycling (NC) and 15 oral contracepting (OC), to sexually explicit photos were measured at three different times. NC women were tested during their menstrual, periovulatory, and luteal phases, and OC women were tested at equivalent temporal intervals. Subjects viewed stimuli as long as desired, thus viewing time measured subject interest. Subjective ratings of stimulus sexual attractiveness were obtained on each test. There was no overall relationship between menstrual cycle phase and viewing time. However the participant's menstrual cycle phase during first exposure to sexual stimuli predicted subsequent interest in sexual stimuli during the next two tests. NC women who first viewed stimuli during their periovulatory phase looked longer at the sexual stimuli across all sessions than did women first tested in their luteal phase. OC women first exposed to the sexual stimuli during menstruation looked longer at the stimuli across all sessions than did OC women first exposed at other test phases. Neither current test phase nor initial cycle phase influenced subjective ratings. Women had increased interest in sexual stimuli across all sessions if first exposed to sexual stimuli when endogenous estrogens were most likely highest. These data suggest that women's interest in visual sexual stimuli is modulated by hormones such that the hormonal condition at first exposure possibly determines the stimuli's emotional valence, markedly affecting subsequent interest in sexual stimuli.

Neural activation in the orbitofrontal cortex in response to male faces increases during the follicular phase.

Women's sexual interest changes with hormonal fluctuations across the menstrual cycle. It is unclear how hormones modify women's sexual behavior and desire, but one possibility is that they alter women's positive appraisals of stimuli and thus their sexual interest. Using 3 T fMRI, we measured neural activation in women at two time points in their menstrual cycle (late follicular, luteal) while they evaluated photos of men presented as potential sexual partners. Participants were ten heterosexual women aged 23-28 none of who was using hormonal contraceptives or in a committed relationship. In an event-related design, the women were presented with as series of photos of male faces and asked questions to assess their degree of sexual interest in the men depicted. Results demonstrate an overall effect of menstrual cycle phase on neural activation. During their follicular versus luteal phase, women demonstrated increased activation in the right medial orbitofrontal cortex (OFC), suggesting increased positive appraisal. Activation in the OFC was positively correlated with women's estradiol to progesterone ratios. There were no areas that demonstrated increased activation during the luteal versus follicular phase. The observed increase in activation in the OFC during the follicular phase may reflect a hormonally mediated increase in appetitive motivation and may prime women towards increased sexual interest and behavior around ovulation.

Neural Activation in Women in Response to Masculinized Male Faces: Mediation by Hormones and Psychosexual Factors.

Women's preference for masculine faces varies with hormonal state, sociosexuality, and relationship status, but the underlying mechanisms are poorly understood. We hypothesized that hormones and psychosexual factors (sociosexuality, sexual inhibition/excitation) mediate the perception and evaluation of male faces thereby influencing women's preferences. We used fMRI to measure brain activity in twelve women as they evaluated pictures of male faces (half 30% masculinized, half 30% feminized). Participants were heterosexual women, age 23-28, who were not in a committed relationship and not using hormonal contraception. Women were tested during both the follicular and luteal phase of their menstrual cycle. We found five brain regions related to face and risk processing that responded more to the masculinized than to the feminized faces, including the superior temporal gyrus, precentral gyrus, posterior cingulate cortex, inferior parietal lobule, and anterior cingulate cortex. Increased activation in the anterior cingulate cortex, specifically, may indicate that women perceive masculinized faces to be both more risky and more attractive. We did not see any areas that were more strongly activated by feminized faces. Levels of activation were influenced by hormonal and psychosexual factors. The patterns of hormonally and psychosexually mediated neural activation observed may offer insight into the cognitive processes underlying women's partner preferences.

The role of the anterior cingulate cortex in women's sexual decision making.

Women's sexual decision making is a complex process balancing the potential rewards of conception and pleasure against the risks of possible low paternal care or sexually transmitted infection. Although neural processes underlying social decision making are suggested to overlap with those involved in economic decision making, the neural systems associated with women's sexual decision making are unknown. Using fMRI, we measured the brain activation of 12 women while they viewed photos of men's faces. Face stimuli were accompanied by information regarding each man's potential risk as a sexual partner, indicated by a written description of the man's number of previous sexual partners and frequency of condom use. Participants were asked to evaluate how likely they would be to have sex with the man depicted. Women reported that they would be more likely to have sex with low compared to high risk men. Stimuli depicting low risk men also elicited stronger activation in the anterior cingulate cortex (ACC), midbrain, and intraparietal sulcus, possibly reflecting an influence of sexual risk on women's attraction, arousal, and attention during their sexual decision making. Activation in the ACC was positively correlated with women's subjective evaluations of sex likelihood and response times during their evaluations of high, but not low risk men. These findings provide evidence that neural systems involved in sexual decision making in women overlap with those described previously to underlie nonsexual decision making.

Sex-specific content preferences for visual sexual stimuli.

Although experimental studies support that men generally respond more to visual sexual stimuli than do women, there is substantial variability in this effect. One potential source of variability is the type of stimuli used that may not be of equal interest to both men and women whose preferences may be dependent upon the activities and situations depicted. The current study investigated whether men and women had preferences for certain types of stimuli. We measured the subjective evaluations and viewing times of 15 men and 30 women (15 using hormonal contraception) to sexually explicit photos. Heterosexual participants viewed 216 pictures that were controlled for the sexual activity depicted, gaze of the female actor, and the proportion of the image that the genital region occupied. Men and women did not differ in their overall interest in the stimuli, indicated by equal subjective ratings and viewing times, although there were preferences for specific types of pictures. Pictures of the opposite sex receiving oral sex were rated as least sexually attractive by all participants and they looked longer at pictures showing the female actor's body. Women rated pictures in which the female actor was looking indirectly at the camera as more attractive, while men did not discriminate by female gaze. Participants did not look as long at close-ups of genitals, and men and women on oral contraceptives rated genital images as less sexually attractive. Together, these data demonstrate sex-specific preferences for specific types of stimuli even when, across stimuli, overall interest was comparable.

Partner Status Influences Women's Interest in the Opposite Sex.

Previous research has demonstrated that hormones, relationship goals, and social context influence interest in the opposite sex. It has not been previously reported, however, whether having a current sexual partner also influences interest in members of the opposite sex. To test this, we obtained explicit and implicit measures of interest by measuring men's and women's subjective ratings and response times while they evaluated photos of opposite-sex faces. Fifty-nine men and 56 women rated 510 photos of opposite-sex faces for realism, masculinity, attractiveness, or affect. We found that these subjective ratings were not influenced by partner status in either men or women. However, women who did not report having a current sexual partner spent more time evaluating the photos than women who did have partners, demonstrating greater interest in the photos. Sexual partner status did not predict men's response times. These findings may reveal that relationship commitment in women suppresses interest in alternative partners.

Sex differences in response to visual sexual stimuli: a review.

This article reviews what is currently known about how men and women respond to the presentation of visual sexual stimuli. While the assumption that men respond more to visual sexual stimuli is generally empirically supported, previous reports of sex differences are confounded by the variable content of the stimuli presented and measurement techniques. We propose that the cognitive processing stage of responding to sexual stimuli is the first stage in which sex differences occur. The divergence between men and women is proposed to occur at this time, reflected in differences in neural activation, and contribute to previously reported sex differences in downstream peripheral physiological responses and subjective reports of sexual arousal. Additionally, this review discusses factors that may contribute to the variability in sex differences observed in response to visual sexual stimuli. Factors include participant variables, such as hormonal state and socialized sexual attitudes, as well as variables specific to the content presented in the stimuli. Based on the literature reviewed, we conclude that content characteristics may differentially produce higher levels of sexual arousal in men and women. Specifically, men appear more influenced by the sex of the actors depicted in the stimuli while women's response may differ with the context presented. Sexual motivation, perceived gender role expectations, and sexual attitudes are possible influences. These differences are of practical importance to future research on sexual arousal that aims to use experimental stimuli comparably appealing to men and women and also for general understanding of cognitive sex differences.

Relationship between testosterone and interest in sexual stimuli: the effect of experience.

Testosterone is commonly thought to drive male sexual interest, but little experimental evidence demonstrates a direct relationship between natural variation in testosterone and sexual interest in healthy young men. This study measured young men's testosterone levels and their interest in visual sexual stimuli across three test sessions within 1 month. Fifteen men aged 23-28 viewed pictures of couples engaged in sexually explicit activity. Each session included a unique set of 72 pictures depicting heterosexual oral sex or intercourse presented in randomized order. Participants controlled how long they viewed each picture, with viewing time indicating sexual interest. Men's testosterone (T) levels were assayed from blood spots obtained prior to viewing the pictures. Overall, T and viewing time were positively correlated; however, the strength of this relationship varied by test session. T was marginally correlated with viewing time during the first session (r=0.43) and not significantly correlated with viewing time on the second session (r=0.16). During the final test session, when habituation might influence male interest in the stimuli, T was strongly correlated with viewing time (r=0.80). Thus, the current study demonstrates a direct but context dependent relationship between testosterone and sexual interest in healthy young males.

Sex differences in viewing sexual stimuli: an eye-tracking study in men and women.

Men and women exhibit different neural, genital, and subjective arousal responses to visual sexual stimuli. The source of these sex differences is unknown. We hypothesized that men and women look differently at sexual stimuli, resulting in different responses. We used eye tracking to measure looking by 15 male and 30 female (15 normal cycling (NC) and 15 oral contracepting (OC)) heterosexual adults viewing sexually explicit photos. NC Women were tested during their menstrual, periovulatory, and luteal phases while Men and OC Women were tested at equivalent intervals, producing three test sessions per individual. Men, NC, and OC Women differed in the relative amounts of first looks towards, percent time looking at, and probability of looking at, defined regions of the pictures. Men spent more time, and had a higher probability of, looking at female faces. NC Women had more first looks towards, spent more time, and had a higher probability of, looking at genitals. OC Women spent more time, and had a higher probability of, looking at contextual regions of pictures, those featuring clothing or background. Groups did not differ in looking at the female body. Menstrual cycle phase did not affect women's looking patterns. However, differences between OC and NC groups suggest hormonal influences on attention to sexual stimuli that were unexplained by subject characteristic differences. Our finding that men and women attend to different aspects of the same visual sexual stimuli could reflect pre-existing cognitive biases that possibly contribute to sex differences in neural, subjective, and physiological arousal.