Is there a significance of histamine in the control of the human male sexual response?

Although histamine has been suggested to be involved in the control of male sexual function, including the induction of penile erection, its role in the human corpus cavernosum penis is still poorly understood. The aim of our study was to evaluate the course of histamine plasma levels through different stages of sexual arousal in the systemic and cavernous blood of healthy male subjects. Thirty four (34) healthy men were exposed to erotic stimuli to elicit penile erection. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Blood was also collected in the post-ejaculatory period. Plasma levels of histamine (ng ml(-1)) were determined by means of a radioimmunoassay. Histamine slightly decreased in the cavernous blood when the penis became tumescent. During rigidity, histamine decreased further but remained unaltered in the phase of detumescence and after ejaculation. In the systemic circulation, no alterations were observed with the initiation or termination of penile erection, whereas a significant drop was registered following ejaculation. Results are not in favour of the hypothesis of an excitatory role of histamine in the control of penile erection. Nevertheless, the amine might mediate biological events during the post-ejaculatory period.     

Is serotonin significant for the control of penile flaccidity and detumescence in the human male?

For more then 15 years, there has been speculation on the significance of serotonergic pathways in the control of male sexual function, especially in the maintenance of penile flaccidity and the initiation of detumescence. However, only a few in vivo studies on peripheral serotonergic transmission have been carried out. The aim of the present study was to evaluate further the effects of serotonin (5-HT) on isolated human erectile tissue and to detect serum levels of 5-HT in the systemic and cavernous blood taken during different penile conditions from healthy males. The effects of 5-HT on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. A total of 41 healthy, adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of 5-HT (ng/ml) were determined by means of an enzyme-linked immunosorbent assay. The cumulative addition of 5-HT (0.001-10 microM) induced contraction in the isolated HCC strips. The contractile response was abolished in the presence of 5-HT(1alpha)-receptor antagonist NAN-190. No attenuating effect of 5-HT was observed on electrically induced relaxation of the tissue. Moreover, amplitudes of relaxation remained unaltered in the presence of NAN-190. In the healthy volunteers, a significant increase in 5-HT levels was detected in the cavernous serum from flaccidity (113+/-62) to tumescence and rigidity (140+/-69 and 141+/-54, respectively), followed by a decrease in the detumescence phase (123+/-79). Changes in 5-HT levels in the systemic serum were less pronounced. Under all penile conditions, systemic 5-HT levels were higher than those registered in the cavernous serum. Although 5-HT does not appear to be involved in postsynaptic transmission in the HCC, our results may provide evidence for a physiological significance of 5-HT in the control of penile flaccidity and detumescence. Thus, our findings may give a rationale for the use of 5-HT antagonists in the pharmacotherapy of erectile dysfunction.     

Is sexual intercourse a significant cause of haematuria?

OBJECTIVES: To determine whether recent sexual intercourse might be a cause of microscopic haematuria in patients referred to a urological unit following dipstick detection of urinary haemoglobin. SUBJECTS AND METHODS: Forty-eight volunteers (24 men and 24 women) consented to have heterosexual intercourse with their regular partner, and to provide samples of urine for testing before and from the first void on the morning after intercourse. After appropriate instruction, volunteers tested their own urine for the presence of blood using standard dipsticks. Any volunteer with haematuria either before or after intercourse was offered a standard haematuria assessment. The results were analysed using the chi-squared test. RESULTS: None of the volunteers tested positively for haematuria immediately before sexual intercourse; six of the 24 women (25%), but no men, became positive after intercourse (P < 0.01). Only one of the six women accepted the offer of a haematuria evaluation and no pathology was identified. CONCLUSION: These results suggest that up to a quarter of women develop microscopic haematuria as a direct result of sexual intercourse. A history of recent sexual intercourse should therefore be considered when assessing the clinical significance of microscopic haematuria in women.     

Is there an inhibitory role of cortisol in the mechanism of male sexual arousal and penile erection?

Background. It has been speculated for more than 2 decades whether there is a significance of adrenal corticosteroids, such as cortisol, in the process of normal male sexual function, especially in the control of sexual arousal and the penile erectile tissue. However, only few in vivo studies have been carried out up until now on the effects of cortisol on human male sexual performance and penile erection. In order to evaluate further the role of cortisol in male sexual activity, the present study was conducted to detect serum levels of cortisol in the systemic and cavernous blood taken during different penile conditions from healthy males. Material and Methods. The effects of cortisol derivative prednisolone, catecholamine norepinephrine (NE) and the peptide endothelin-1 (ET-1) on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. Fifty-four healthy adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of cortisol (g/dl) were determined by means of a radioimmunoassay (ELISA). Results. In the healthy volunteers, cortisol serum levels significantly decreased in the systemic circulation and the cavernous blood with increasing sexual arousal, when the flaccid penis became rigid. During detumescence, the mean cortisol level remained unaltered in the systemic circulation, whereas in the cavernous compartment, it was found to decrease further. Under all penile conditions, no significant differences were registered between cortisol levels in the systemic circulation and in the cavernous blood. Cumulative addition of NE and ET-1 (0.001–10 M) induced contraction of isolated HCC strips, whereas the contractile response to prednisolone was negligible. Conclusion. Our results strongly suggest an inhibitory role for cortisol in the mechanism of male sexual response and behaviour. These properties are mediated rather via an effect on central structures than on the penile erectile tissue. Future studies to include patients suffering from erectile dysfunction may reveal whether or not there are differences in the cortisol serum profiles of healthy subjects and patients under different stages of sexual arousal.     

Altered TGF‐β signaling in fetal fibroblasts: What is known about the underlying mechanisms?

Scarless wound healing is a unique and intrinsic capacity of the fetal skin that is not fully understood. Further insight into the underlying mechanisms of fetal wound healing may lead to new therapeutic approaches promoting adult scarless wound healing. Differences between fetal and adult wound healing are found in the extracellular matrix, the inflammatory reaction and the levels of growth factors present in the wound. This review focuses specifically on transforming growth factor β (TGF‐β), as this growth factor is prominently involved in wound healing and fibroblast‐to‐myofibroblast differentiation. Although fetal fibroblasts do respond to TGF‐β, they lack a proliferative and a contractile response and display short‐lived myofibroblast differentiation, autocrine response, and collagen up‐regulation in comparison with adult fibroblasts. Curiously, prolonged TGF‐β activation is associated with fibrosis, and therefore, this short‐lived response in fetal fibroblasts might contribute to scarless healing. This review gives an overview of the current knowledge on TGF‐β signaling and the intracellular TGF‐β signaling pathway in fetal fibroblasts. Furthermore, this review also describes the various components that regulate the cellular TGF‐β response and hypothesizes about the possible roles these components might play in the altered response of fetal fibroblasts to TGF‐β.     

Is the presence of venous reflux really significant in the diagnosis of varicocele?

Objectives  We have attempted to determine the incidence of venous reflux detected by color Doppler in varicoceles of various grades evaluated during a physical examination. Patients and methods  The data of patients referred to our outpatient clinic between 1997 and 2007 with the diagnosis of varicocele due to complaints of scrotal pain, palpable swelling or infertility were retrospectively reviewed. The presence of venous reflux was compared with the grade of varicoceles during a physical examination. Results  A total of 802 male patients with a mean age of 27.1 years (range 16–52 years) were included in this study. Of these, physical examination reviewed that ten (1.2%), 72 (9.0%), 433 (54.0%) and 287 (35.8%) patients had grade 0, 1, 2 or 3 varicoceles, respectively, on the left side and that 607 (75.7%), 73 (9.1%), 108 (13.5%) and 14 (1.7%) patients had grade 0, 1, 2 or 3 varicoceles, respectively, on the right side. Color Doppler examination revealed venous reflux in three (30.0%) grade 0 testicular units, 63 (87.5%) grade 1 testicular units, 400 (92.4%) grade 2 testicular units and 273 (95.1%) grade 3 testicular units on the left side and venous reflux in 99 (16.3%) grade 0 testicular units, 54 (73.6%) grade 1 testicular units, 88 (81.5%) grade 2 testicular units and 12 (85.7%) grade 3 testicular units on the right side. Physical examination did not reveal any statistically significant correlation between the incidence of venous reflux and the grade of the clinically evident varicoceles for both sides. Conclusions  For assessing the severity of clinically evident varicoceles, the clinician should not use venous reflux as the sole predictor because of its high incidence in all grades of varicoceles. Additional measurements, such as flow volume, duration and velocity of reflux, are recommended as diagnostic tools for assessing the severity of varicocele more accurately.     

Is the clinical malignant phenotype of prostate cancer a result of a highly proliferative immune‐evasive B7‐H3‐expressing cell population?

Objectives: To assess the expression of the cell surface protein B7‐H3 in prostate cancer, and its association to clinically relevant parameters after radical prostatectomy and to the proliferation marker Ki‐67. Methods: Radical prostatectomy specimens from a cohort of 130 patients with a median clinical follow up of 8 years were used for the analysis. The expression of B7‐H3 and the proliferation marker Ki‐67, as well as other standard clinicopathological parameters, were evaluated. Results: A high expression of B7‐H3 was associated with pathological stage T3a and T3b, high Gleason score, extraprostatic extension, seminal vesicle invasion and high proliferative activity. Univariable analysis showed that a high expression level of B7‐H3 was also correlated with biochemical failure and clinical relapse, and with the expression of Ki‐67. A high expression level of Ki‐67 was associated with clinical progression and a tendency towards higher rates of prostate‐specific antigen relapse in multivariate analyses. Conclusions: Our findings show that a high expression level of B7‐H3 in prostate cancer correlates with the expression of the proliferation marker Ki‐67, biochemical failure and clinical relapse. Thus, expression of the cell surface molecule B7‐H3 adds to the malignant phenotype of prostate cancer cells expressing high levels of Ki‐67. The impact of B7‐H3 function on prostate cancer and its potential role in immunotherapy should be explored further.     

Does transforming growth factor β1 play a role in the pathogenesis of chronic allograft rejection?

To investigate the potential role of Transforming Growth Factor β1 (TGFβ1) in the pathogenesis of chronic allograft rejection, we studied TGFβ1 expression in a rat aortic allograft model. mRNA and protein expression of total and endogenously active TGFβ1 were analysed in infra-renal orthotopic aortic syngeneic and allogeneic grafts and matched with the histological appearances of the grafts, 2, 4 and 12 weeks post-transplantation. Serum levels of TGFβ1 were also measured. The level of TGFβ1 m RNA and protein expression appeared highest 2 and 4 weeks following transplantation in both syngeneic and allogeneic grafts, with significantly elevated levels of mRNA expression in the 2 week allograft specimens. These time-points correlate histologically with maximal inflammatory cell infiltration of the grafts. By 12 weeks post-transplantation, TGFβ1 mRNA expression is reduced in allogeneic grafts compared to syngeneic grafts. However, detectable levels of total and endogenously active TGFβ1 protein levels in the allografts exceed those measured in the syngeneic grafts at this time point. These results demonstrate the complex expression pattern of this growth factor during the progression of chronic rejection and suggest an aetiological link between TGFβ1 and the process of accelerated graft atherosclerosis. Received: 24 July 1998 Received after revision: 18 May 1999 Accepted: 12 July 1999     

Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy

Nitrogen‐bisphosphonates (n‐BP), often referred to as aminobisphosphonates, are the most commonly prescribed drugs for the treatment of disorders of bone fragility. However, long‐term continuous treatment predisposes certain individuals to serious rare side effects, such as bisphosphonate‐associated osteonecrosis of the jaw (BAONJ). n‐BP use is known to unintentionally activate a subset of innate T cells called Vγ9Vδ2 T cells, but the consequence of this chronic immune stimulation has remained unexplored. The primary objectives of this study were to 1) determine the fate of Vγ9Vδ2 T cells in osteoporotic patients on n‐BP therapy as a function of time and type of therapy; 2) evaluate the proportion of Vγ9Vδ2 T cells in patients who had recently experienced n‐BP–associated ONJ. We found there is a notable loss of Vγ9Vδ2 T cells over time in osteoporotic patients on n‐BP therapy, particularly those on intravenous (iv) therapy (Spearman r = ?0.55, p < 0.0001 iv; r = ?0.3, p < 0.03 oral) (n = 68); no difference was observed in total T cells, monocytes, or granulocytes. Importantly, the observed negative effect on Vγ9Vδ2 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ. Patients (n = 6) who had experienced BAONJ were all found to be significantly deficient in Vγ9Vδ2 T cells (median = 0.07%) in comparison to age‐ and sex‐matched treatment‐naïve controls (N = 11; median = 2.40%), U = 0, p = 0.001; this was the only consistent difference in the leukocytes assessed. All BAONJ cases had an underlying condition that further contributed to impaired immunity. We propose Vγ9Vδ2 T cells show a strong potential to serve as harbingers of possible adverse immune effects of n‐BP therapy, particularly in those patients already having a compromised immune system as they may be most vulnerable to the development of conditions such as BAONJ. © 2013 American Society for Bone and Mineral Research.