Neutrophil adherence to cytokine-activated endothelial cell (EC) monolayers depends on the expression of the endothelial leukocyte adhesion molecule-1 (ELAM-1). The ligand for ELAM-1 is the ...sialylated Lewis-x antigen ( SLex) structure. The selectin LAM-1 (or LECAM-1) has been described as one of the SLex-presenting glycoproteins involved in neutrophil binding to ELAM-1. Other presenter molecules have not yet been described. Our data demonstrate that the carcinoembryonic antigen (CEA)-like surface molecules on neutrophils-known as the nonspecific cross-reacting antigens (NCAs)-are involved in neutrophil adherence to monolayers of IL-1-β-activated EC. The NCAs are recognized by CD66 (NCA-160 and NCA-90) and CD67 (NCA-95). Because NCA-95 and NCA-90 have previously been found to be phosphatidylinositol (PI)-linked, paroxysmal nocturnal hemoglobinuria (PNH) neutrophils (which lack PI-linked surface proteins) were tested as well. PNH neutrophils showed a diminished binding to activated EC. CD66 (on PNH cells still recognizing the transmembrane NCA-160 form) still inhibited the adherence of PNH cells to IL-1-β-activated EC, but to a limited extent. Soluble CEA(-related) antigens inhibited normal neutrophil adherence as well, whereas neutrophil transmigration was unaffected. Sialidase-treatment as well as CD66 preclearing abolished the inhibitory capacity of the CEA(-related) antigens. The binding of soluble CEA antigens to IL-1-β-pretreated EC was blocked by anti-ELAM-1. These soluble antigens, as well as the neutrophil NCA-160 and NCA-90, both recognized by CD66 antibodies, presented the SLexdeterminant. Together, these findings indicate that the CD66 antigens (i.e., NCA-160/NCA-90) function as presenter molecules of the SLexoligosaccharide structures on neutrophils that bind to ELAM-1 on EC.
Current views suggest that in women with superficial dyspareunia the prospect of penile–vaginal intercourse automatically activates fear-related associations. The automatic activation of negative ...associations is assumed to interfere with the development of sexual arousal. In turn, this may further aggravate the dyspareunia-related complaints. To assess whether automatic negative associations are involved in this sexual pain disorder, women with superficial dyspareunia (
n
= 35) and a control group (
n
= 35) completed a modified pictorial Affective Simon Task (AST). Questioning the role of dysfunctional automatic associations in superficial dyspareunia, the AST indicated that symptomatic women displayed relatively positive rather than negative automatic associations with sexual stimuli. At the self-report level, however, affective associations with sex cues were significantly more negative for women with dyspareunia than for controls. This discrepancy between “reflective” and “reflexive” affective associations with sexual stimuli in women with dyspareunia points to the relevance of conscious appraisal and deliberate rather than automatic processes in the onset and maintenance of dyspareunia.
Sexual abuse is a risk factor for developing various abdominal and pelvic complaints. In this clinical lesson we present one case, highlighting this connection and how it can be missed by different ...medical professionals. Early identification of the underlying connection with sexual abuse can prevent re-traumatization by medical treatments, reduce the risk of the patient being abused again and raises the opportunity for a more appropriate treatment, such as addition or trauma therapy and/or pelvic physiotherapy.
Recently, a novel murine member of the scavenger receptor class A family, designated MARCO, has been cloned
4. Scavenger receptors have a characteristic broad ligand specificity and are able to bind ...various substances, including bacteria cell surface components. The receptor MARCO is expressed by a distinct subset of macrophages in spleen and lymph nodes. Using a panel of monoclonal antibodies (mAbs) specifically directed against MARCO, we investigated the regulation of this receptor in vitro and in vivo. Stimulation of the mouse macrophage cell line J774.2 in vitro with bacterial lipopolysaccharides (LPS) induces upregulation of MARCO surface expression. In accordance with this observation, in mice suffering from endotoxin shock caused by bacterial infection, expression of MARCO is induced on macrophages in the liver, lung and spleen, which normally do not express this receptor. We found that two of the anti-MARCO mAbs, ED29 and ED31, were able to block ligand binding. They inhibited the uptake of heat-killed
Escherichia coli by MARCO expressing CHO cells. Further experiments will be needed to confirm the importance of MARCO in the anti-bacterial host defense.
Prolapse surgery has been shown to have major impact on sexual function. Since prolapse surgery not only influences psychological factors but might also influence physiological conditions such as ...vaginal innervation, there is a need for objective outcome measurements to better understand the effects of prolapse surgery on sexual function.
To assess the effects of prolapse surgery with or without stress incontinence surgery on vaginal sensibility and to assess the relationship between vaginal wall sensibility and sexual well‐being.
This study was performed parallel to a randomized controlled trial comparing vaginal and abdominal prolapse surgery with or without incontinence surgery in women with uterine prolapse stage 2 or more.
Vaginal wall sensibility was defined as mean sensation threshold to electrical stimulation of the vaginal wall at four standardized places, measured before and 6 months after surgery. Higher sensation thresholds postsurgery relative to presurgery indicate diminished vaginal wall sensibility. Sexual function was assessed at the same time points using a questionnaire.
Data on vaginal wall sensibility were obtained from 65 patients. The sensibility of the distal posterior (P = 0.02) and distal anterior (P = 0.10) vaginal wall decreased after vaginal surgery compared to abdominal surgery. Abdominal prolapse surgery with incontinence surgery decreased sensibility of the distal part of the anterior vaginal wall significantly more than abdominal prolapse surgery only (P = 0.01). Before surgery, vaginal wall sensibility was lower in women who reported vaginal dryness or anorgasmia. The presence of genital pain was associated with higher vaginal wall sensibility. Postoperative vaginal wall sensibility was similar in women with and without sexual problems.
Vaginal prolapse surgery as well as abdominal prolapse surgery with additional incontinence surgery resulted in decreased vaginal wall sensibility. This pilot study shows no influence of the decreased vaginal wall sensibility on sexual well‐being. Larger studies are needed to better understand the association between changes in vaginal wall sensibility and changes in sexual well‐being. Lakeman MME, van der Vaart CH, Laan E, and Roovers J‐PWR. The effect of prolapse surgery on vaginal sensibility..
To better evaluate efficacy in clinical trials of drugs as potential treatments for female sexual dysfunctions (FSD), a brief, multidimensional measure of female sexual function was developed.
Data ...from semistructured interviews with 82 women with or without FSD, aged 19-65 years, generated a pool of 61 items that addressed aspects of female sexual function. On review by a panel, individual items were selected for face validity and clinical relevance. Thirty-one items were used as a sexual function questionnaire (SFQ-V1) in two multicenter, phase II clinical trials totaling 781 women with FSD. Normative data were generated from a sample of 201 women without FSD.
Factor analysis produced seven domains of female sexual function: desire, physical arousal-sensation, physical arousal-lubrication, enjoyment, orgasm, pain, and partner relationship. The internal consistency of the domains ranged from 0.65 to 0.91, and test-retest reliability ranged from 0.21 to 0.71 for Cohen's weighted kappa and 0.42 to 0.78 for Pearson's correlation coefficient. There was a significant difference between the baseline mean SFQ domain scores of patients with FSD compared with those of women without FSD (p < 0.0001). End-of-study SFQ scores were significantly different for women who reported improvement vs. women who reported no improvement (p < 0.001).
The SFQ produced seven domains of female sexual function with excellent internal consistency, moderate to good reliability, excellent discriminant validity, and sensitivity. The results suggest that the SFQ may be a valuable new tool for evaluating and diagnosing subsets of FSD and, ultimately, for evaluating treatments of these disorders.
This study examined the effect of a single oral dose of sildenafil citrate (Viagra, Pfizer, Inc., New York, NY) on vaginal vasocongestion and subjective sexual arousal in healthy premenopausal women.
...Twelve women without sexual dysfunction were randomly assigned to receive either a single oral 50 mg dose of sildenafil or matching placebo in a first session and the alternate medication in a second session. Subjective measures of sexual arousal were assessed after participants had been exposed to erotic stimulus conditions. Vaginal vasocongestion was recorded continuously during baseline, neutral, and erotic stimulus conditions. At the end of each session, subjects were also asked to specify which treatment they suspected they had received.
Significant increases in vaginal vasocongestion were found with sildenafil treatment compared with placebo. There were no differences between treatments on subjective sexual arousal experience. Analyses by suspected treatment received found that significantly stronger sexual arousal and vaginal wetness were reported for the treatment that was believed to be sildenafil vs. the treatment that was believed to be placebo. The suspected treatment sequence was incorrect for half of the women. Sildenafil was well tolerated, with no evidence of significant adverse events.
Sildenafil was found to be effective in enhancing vaginal engorgement during erotic stimulus conditions in healthy women without sexual dysfunction but was not associated with an effect on subjective sexual arousal.
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