| 1. |
- Andersson, Karl-Erik, et al.
(författare)
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New directions for erectile dysfunction therapies
- 2002
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Ingår i: International journal of impotence research. - : Nature Publishing Group. - 0955-9930 .- 1476-5489. ; 14 Suppl 1, s. S82-S92
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Tidskriftsartikel (refereegranskat)abstract
- Research in the field of erectile function and dysfunction has continued to expand rapidly. Based on the information available, some directions for future erectile dysfunction therapies can be identified. The first direction is improvement of current therapeutic principles. A second generation of orally active phosphodiesterase (PDE) inhibitors is being introduced, and further developments within this field can be expected. The recent introduction of apomorphine has opened the way for new dopamine receptor agonists. The second direction is combinations of existing therapeutic principles. Combinations of apomorphine and sildenafil and apomorphine and alpha(1)-adrenoceptor (AR) antagonists, for example, seem attractive and may have a therapeutic potential in patients not responding satisfactorily to single-drug treatment. Nitrosylated alpha(1)-AR antagonists, combining nitric oxide donation and alpha(1)- or alpha(2)-AR antagonism, are currently being evaluated. The third direction is new targets within the central nervous system. Melanocortin receptor agonists have shown promise not only in animal models, but also in preliminary studies in humans. Other possible targets, such as growth hormone-releasing peptide receptors, are being explored. The fourth direction is new peripheral targets. Rho-kinase antagonism and non-nitric oxide-mediated stimulation of soluble guanylyl cyclase have been suggested as possible new principles for drug development. The fourth direction is gene therapy. Progress has been made in intracavernosal somatic gene therapy and will probably continue. Still, problems remain, and advantages over conventional pharmacological therapies have to be demonstrated. The final direction is prevention strategies. Strategies to prevent cavernosal degeneration and/or to restore cavernosal function will be one of the most exciting challenges for future research.
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| 2. |
- Andersson, Karl-Erik, et al.
(författare)
-
New directions for erectile dysfunction therapies.
- 2002
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Ingår i: International Journal of Impotence Research. - 1476-5489. ; 14 Suppl 1, s. 82-92
-
Tidskriftsartikel (refereegranskat)abstract
- Research in the field of erectile function and dysfunction has continued to expand rapidly. Based on the information available, some directions for future erectile dysfunction therapies can be identified. The first direction is improvement of current therapeutic principles. A second generation of orally active phosphodiesterase (PDE) inhibitors is being introduced, and further developments within this field can be expected. The recent introduction of apomorphine has opened the way for new dopamine receptor agonists. The second direction is combinations of existing therapeutic principles. Combinations of apomorphine and sildenafil and apomorphine and alpha(1)-adrenoceptor (AR) antagonists, for example, seem attractive and may have a therapeutic potential in patients not responding satisfactorily to single-drug treatment. Nitrosylated alpha(1)-AR antagonists, combining nitric oxide donation and alpha(1)- or alpha(2)-AR antagonism, are currently being evaluated. The third direction is new targets within the central nervous system. Melanocortin receptor agonists have shown promise not only in animal models, but also in preliminary studies in humans. Other possible targets, such as growth hormone-releasing peptide receptors, are being explored. The fourth direction is new peripheral targets. Rho-kinase antagonism and non-nitric oxide-mediated stimulation of soluble guanylyl cyclase have been suggested as possible new principles for drug development. The fourth direction is gene therapy. Progress has been made in intracavernosal somatic gene therapy and will probably continue. Still, problems remain, and advantages over conventional pharmacological therapies have to be demonstrated. The final direction is prevention strategies. Strategies to prevent cavernosal degeneration and/or to restore cavernosal function will be one of the most exciting challenges for future research. DOI: 10.1038/sj/ijir/3900797
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| 3. |
- Andersson, KE, et al.
(författare)
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Sympathetic pathways and adrenergic innervation of the penis
- 2000
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Ingår i: International journal of impotence research. - : Nature Publishing Group. - 0955-9930 .- 1476-5489. ; 12, s. S5-S12
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Tidskriftsartikel (refereegranskat)abstract
- The sympathetic nervous system is important for penile function: it mediates detumescence and may contribute to the maintenance of the penis in a non-erect state. The sympathetic preganglionic neurons are found in the intermediolateral gray matter of the spinal cord. Postganglionic neurons are located to the sympathetic chain ganglia, the inferior mesenteric, hypogastric and pelvic ganglia, and possibly to ganglia near the target organ. Sympathetic fibres can be found in the pelvic, cavernous, and pudendal nerves. Stimulation of the sympathetic pathways to the penis may, however, also produce erection. It has been suggested that the suprasacral vasodilator pathway is a sympathetic cholinergic pathway, operating through cholinergic neurons in the pelvic plexus. In the penis, there is a rich sympathetic, adrenergic innervation of the corpus cavernosum (CC) and the vasculature, and in particular of the helicine arteries. Sympathetic, adrenergic nerves also contain neuropeptide Y. Parasympathetic cholinergic nerves, which mediate CC relaxation and erection, contain not only acetylcholine, but also vasoactive intestinal polypeptide, nitric oxide synthase, and probably other mediators and/or mediator-synthesizing enzymes. Activation of sympathetic adrenergic nerves causes release of noradrenaline, acting on alpha-adrenoceptors in the trabecular smooth muscle of the CC and in penile vessels. The role of interactions between different transmitters and mediators, released from nerves or generated locally, in the regulation of contraction and relaxation of CC and penile vessels, needs further study.
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| 4. |
- Carlsson, S, et al.
(författare)
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Self-perceived penile shortening after radical prostatectomy.
- 2012
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Ingår i: International journal of impotence research. - : Springer Science and Business Media LLC. - 1476-5489 .- 0955-9930. ; 24:5, s. 179-84
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Tidskriftsartikel (refereegranskat)abstract
- The postoperative effect on penile length after radical prostatectomy has been the subject of studies with conflicting results. We analyzed self-perceived penile shortening, quality of life and self-esteem after radical prostatectomy. In this cross-sectional study of a cohort of 1411 men who underwent a radical prostatectomy at Karolinska University Hospital between 2002 and 2006, we used a study-specific questionnaire. Patients and controls were asked about their perceived penile shortening by comparing present penile length now and at age 30 years. All subjects were also asked about their present quality of life and self-esteem. Patients were compared with 442 age-matched population-based controls. Among 1288 who underwent radical prostatectomy and answered the questionnaire (response rate 91%), 663 patients reported self-perceived penile shortening (55%), as compared with 85 (26%) of 350 men in the control group, corresponding to a relative risk (RR) of 2.1 (95% confidence interval (CI) 1.8-2.6) of self-perceived penile shortening compared with the age-matched control group. Age, grade of erectile dysfunction and angina were correlated with self-perceived penile shortening in both the operated and the control group. After adjustments for all of these mentioned potential confounders, we obtained a RR of 1.7 (95% CI 1.4-2.1) of self-perceived penile shortening compared with the controls. We also found that self-assessed penile shortening was associated with a RR of 1.2 (95% CI 1.1-1.3) for a low-to-moderate self-assessed quality of life and a RR of 1.2 (95% CI 1.1-1.4) for a low-to-moderate self estimation of self-esteem. Extensive nerve-sparing technique seems to be associated with less self-perceived penile shortening compared with radical prostatectomy with lower degree of nerve-sparing approach. These data indicate that radical prostatectomy is associated with self-perceived penile shortening and suggests that erectile function is a key factor in penile shortening.
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| 5. |
- Castiglione, Fabio, et al.
(författare)
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Long-term consequences of bilateral cavernous crush injury in normal and diabetic rats : a functional study
- 2022
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 0955-9930 .- 1476-5489. ; 34:8, s. 781-785
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Tidskriftsartikel (refereegranskat)abstract
- A recent statement from the European-Society-for-Sexual-Medicine has highlighted the limitations of using the rat model for nerve-sparing prostatectomy. The use of young rats with no comorbidities and the early evaluation of the erectile function (EF) are deemed a source of bias. Our aim was to evaluate the long-term consequences in EF of bilateral nerve cavernous crush- injury (BNCI) in type 1 diabetic (DM) rats 30-male/12-week-old rats were divided into four groups: Sham, BNCI, DM, and BNCI + DM. Sham group underwent an intraperitoneal injection (IP) of saline solution and after 1 month underwent a sham laparotomy. BNCI underwent an IP of saline solution and after 1 month to BNCI. DM underwent an IP of 60 mg/kg-1-streptozotocin (STZ) and after 1 month to a sham laparotomy. BNCI + DM underwent an IP of 60 mg/kg-1-STZ and after 1 month to BNCI. After 5 months from the induction of diabetes, all rats underwent measurement of intracorporeal pressure (ICP) and mean arterial pressure (MAP) during CN-electrostimulation. Multiple groups were compared using Kruskal–Wallis one-way analysis of variance followed by Mann–Whitney U test for post hoc comparisons. Blood glucose-level was higher (p < 0.05) in the groups with DM and BNCI + DM. After 5-months, DM and BNCI + DM also showed a lower weight compared to other groups (p < 0.05). No differences were noted in ICP/MAP between the sham and BNCI. BNCI + DM showed lower ICP/MAP compared to all the groups (p < 0.05). DM Showed lower ICP/MAP compared to Sham and BNCI (p < 0.05). BNCI in rats without comorbidities did not induce long-term erectile dysfunction (ED) suggesting a spontaneous EF recovery. BNCI in DM induced long-term ED. The results of previous short-term studies can only provide evidence on the time to recovery of spontaneous EF as to the actual EF recovery rate.
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| 6. |
- Earp, Brian D, et al.
(författare)
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Current critiques of the WHO policy on female genital mutilation
- 2021
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Ingår i: International journal of impotence research. - : Nature Publishing Group. - 0955-9930 .- 1476-5489. ; 33, s. 196-209
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, the dominant Western discourse on "female genital mutilation" (FGM) has increasingly been challenged by scholars. Numerous researchers contest both the terminology used and the empirical claims made in what has come to be called "the standard tale" of FGM (also termed "female genital cutting" [FGC]). The World Health Organization (WHO), a major player in setting the global agenda on this issue, maintains that all medically unnecessary cutting of the external female genitalia, no matter how slight, should be banned as torture and a violation of the human right to bodily integrity. However, the WHO targets only non-Western forms of female-only genital cutting, raising concerns about gender bias and cultural imperialism. Here, we summarize ongoing critiques of the WHO's terminology, ethicolegal assumptions, and empirical claims, including the claim that non-Western FGC as such constitutes an extreme form of discrimination against women. To this end, we highlight recent comparative studies of medically unnecessary genital cutting of all types, including those affecting adult women and teenagers in Western societies, individuals with differences of sex development (DSD), transgender persons, and males. In so doing, we attempt to clarify the grounds for a growing critical consensus that current anti-FGM laws and policies may be ethically incoherent, empirically unsupportable, and legally unsustainable.
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| 7. |
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| 8. |
- Giraldi, A, et al.
(författare)
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Effects of diabetes on neurotransmission in rat vaginal smooth muscle
- 2001
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 1476-5489 .- 0955-9930. ; 13:2, s. 58-66
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to characterize the effect of experimental diabetes on neurotransmission in rat vagina. Female Sprague-Dawley rats were divided into two groups: non-diabetic controls (NDM, n=38) and diabetics (DM, n=38). DM was produced by intraperitoneal injection of streptozotocin. Eight weeks later the animals were killed, the distal part of the vagina was removed, and smooth muscle strips were prepared for functional organ bath experiments and for measurement of nitric oxide synthase (NOS) activity. In DM preparations, the EC(50) value for noradrenaline (NA) was significantly increased (P<0.05) and the maximal contractile response decreased (P=0.001). In preparations precontracted with NA, the NO donor SNAP and calcitonin gene-related peptide (CGRP) caused concentration-dependent relaxations, which were significantly decreased (P<0.001) in the DM group. Electrical stimulation of nerves (EFS) caused frequency-dependent contractions, which were significantly lower in DM than in NDM strips (P<0.001). SNAP and CGRP concentration-dependently inhibited EFS evoked contractions in both NDM and DM preparations. The inhibition was significantly lower (P<0.05) in the DM group. In NDM preparations precontracted with NA, EFS evoked frequency-dependent relaxations; such relaxations were inhibited or reduced in DM. Treatment with the NOS inhibitor, L-NOARG 0.1 mM, abolished relaxations in all preparations or produced contraction in DM preparations. Calcium-dependent NOS activity was not significantly different in the DM and NDM groups. However, the DM animals showed a small but significant increase in calcium-independent NOS-activity (P<0.05). Diabetes interferes with adrenergic-, cholinergic- and NANC-neurotransmitter mechanisms in the smooth muscle of the rat vagina. The changes in the nitrergic neurotransmission are not due to reduction in NOS-activity, but seem to be due to interference with later steps in the L-arginine/NO/guanylate cyclase/cGMP system.
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| 9. |
- Giraldi, A, et al.
(författare)
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Morphological and functional characterization of a rat vaginal smooth muscle sphincter
- 2002
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 1476-5489 .- 0955-9930. ; 14:4, s. 271-282
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to gain information about adrenergic-, cholinergic- and nonadrenergic, non-cholinergic (NANC)- transmitter systems/mediators in the rat vagina, and to characterize its smooth muscles functionally. Tissue sections from vagina of Sprague Dawley rats were immunolabelled with antibodies against protein gene product 9.5 (PGP), synaptophysin (Syn), tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Circularly cut vaginal smooth muscle preparations from the distal vagina were studied in organ baths. In the paravaginal tissue, a large number of PGP-, NOS-, TH-, VIP-immunoreactive (IR) and few CGRP-IR nerve trunks were observed, giving off branches to the smooth muscle wall. The smooth muscle wall was supplied by a large number of PGP-, Syn-, VAChT-, NPY-, NOS- and TH- IR nerve terminals, whilst only a moderate to few numbers of CGRP-, VIP- and PACAP-IR terminals were identified. Especially the distal part of the vaginal wall, where the circularly running smooth muscle was thickened into a distinct sphincter structure, was very richly innervated, predominantly by PGP- and NOS-IR terminals. Below and within the basal parts of the epithelium in the distal half of the vagina, a large number of PGP- and few NOS- and PACAP-IR varicose terminals were observed. The vaginal arteries were encircled by plexuses of nerve terminals. A large number of these were PGP-, Syn-, VAChT-, NOS-, TH-, NPY- and VIP-IR, and few were CGRP- and PACAP-IR. In isolated preparations of the distal vagina, electrical field stimulation (EFS) caused frequency-dependent contractions, which were reduced by sildenafil, tetrodotoxin (TTX) and phentolamine. In preparations contracted by norepinephrine (NA), EFS produced frequency-dependent relaxations. Pretreatment with the NOS-inhibitor N-G-nitro-L-arginine, TTX, or the inhibitor of soluble guanylate cyclase, ODQ, abolished the EFS relaxations. In NE precontracted preparations, cumulative addition of sildenafil caused concentration-dependent relaxation. Carbachol contracted the strips concentration-dependently from baseline. It can be concluded that the distal part of the rat vagina forms a distinct smooth muscle sphincter, which is richly innervated by adrenergic, cholinergic and NANC nerves. The present studies suggest that in the rat the L-arginine/NO-system not only plays an important role in the regulation of vaginal smooth muscle tone, but also affects blood flow, and may have sensory functions.
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| 10. |
- Hakim, Lukman, et al.
(författare)
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Intratunical injection of autologous adipose stromal vascular fraction reduces collagen III expression in a rat model of chronic penile fibrosis
- 2019
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 0955-9930 .- 1476-5489.
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that the injection of adipose stem cells and stromal vascular fraction(SVF) into the tunica albuginea (TA) during the inflammatory phase in a rat model of Peyronie’s disease(PD) prevented the development of TA fibrosis. Our aim was to investigate whether local injection of SVF can reduce established fibrosis in a rat model of chronic phase of PD. Eighteen-male 12-wk-old Sprague-Dawley rats were divided in three equal groups: sham, PD without treatment (PD) and PD treated with SVF(PD-SVF). Sham rats underwent 2 injections of vehicle into the TA one month apart. PD rats underwent TGF-β1 injection and injection of vehicle one month later. PD-SVF rats underwent TGF-β1 injection followed by SVF (1-million cells) one month later. One month after the last treatment, the animals, n = 6 rats per group, underwent measurement of intracorporal and mean arterial pressure during electrostimulation of the cavernous nerve. Following euthanasia, penises were harvested for in-vitro study. Erectile function was not statistically significantly different between groups. PD animals developed subtunical areas of fibrosis and elastosis with upregulation of collagen III protein. These fibrotic changes were reversed after injection of SVF. We provide evidence that local injection of SVF reverses TA fibrosis in a rat model of chronic phase of PD.
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| 11. |
- Ishizuka, O, et al.
(författare)
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Effect of apomorphine on intracavernous pressure and blood pressure in conscious, spinalized rats
- 2002
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Ingår i: International Journal of Impotence Research. - 1476-5489. ; 14:2, s. 128-132
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Tidskriftsartikel (refereegranskat)abstract
- Apomorphine, given subcutaneously (s.c.), induces erection and bladder overactivity in rats through stimulation of dopamine (D1- and D2-like) receptors in the central nervous system. In paraplegic patients, apomorphine was reported to cause bladder overactivity. This suggests that apomorphine may have a spinal site of action also for stimulation of erection. The present study was initiated to evaluate the effect of apomorphine on erectile function in spinalized rats. Apomorphine (100 mug/kg, s.c.) was given to awake. unrestrained male Sprague-Dawley rats (300 g) with or without spinal cord injure, made at the Th 8 level 2 weeks before the experiment. Intracavernous pressure changes from baseline were evaluated as time to first response to apomorphine (TFR; see), number of phasic pressure changes in the first 30 min (PP30), duration (113; see) of the phasic pressure changes, the amount of increase in tonic peak pressure (TPP; cmH(2)O), and burst peak pressure (BPP, cmH(2)O). Blood pressure (cmH(2)O) was recorded via an intra-arterial catheter. Apomorphine, 100 mug/kg, caused no significant differences in TFR (217.8 vs 271.2), PP30 (6.4 vs 6.5), D (38.9 vs 37.6.), TPP (51.0 vs 54.0) and BPP (128.9 vs 160.4) between normal (n = 8) and spinalized rats (n = 6). However, blood pressure decreased significantly more in spinalized than in normal animals (17.7 vs 43.3: P < 0.05). The results suggest that both in normal rats, and in rats with spinal cord injury, apomorphine given s.c., can produce erection. This finding supports the use of apomorphine for treatment of erectile dysfunction in paraplegia patients. However, due consideration should be given to possible decreases in blood pressure.
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| 12. |
- Jern, P, et al.
(författare)
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Antidepressant treatment of premature ejaculation: discontinuation rates and prevalence of side effects for dapoxetine and paroxetine in a naturalistic setting.
- 2015
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Ingår i: International journal of impotence research. - : Springer Science and Business Media LLC. - 1476-5489 .- 0955-9930. ; 27:2, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to investigate prevalence of and reasons for selective serotonin reuptake inhibitor (SSRI) discontinuation, and compare the two most common SSRIs used in premature ejaculation (PE) treatment, in naturalistic settings (that is, outside clinical trials). The sample consisted of 132 Finnish men with a mean age of 42.5 years (s.d.=10.6) who had received medical treatment for lifelong PE. The men were enlisted for the study after identifying individuals from the third author's (a physician specializing in sexual medicine) patient registry. Participants responded to a secure, online questionnaire. PE treatment-related side effects of, and discontinuation rates for, different SSRIs were retrospectively self-reported. Treatment efficacy and happiness with treatment were retrospectively self-assessed. Discontinuation rates were uniformly high, ranging from 28.8 to 70.6% between different SSRIs. Dapoxetine was associated with the highest dropout rates (70.6%), and paroxetine the lowest, discontinuation rates. Limited efficacy and side effects were the most common reasons for discontinuation. Paroxetine was more effective and better tolerated than dapoxetine. A considerable number of patients chose to spontaneously discontinue treatment, especially so in the case of dapoxetine, corroborating recent studies conducted in naturalistic settings. Further research efforts are necessary to develop new and improve existing PE treatment alternatives.
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| 13. |
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| 14. |
- Kutlu, O., et al.
(författare)
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Increased expression of nestin in the major pelvic ganglion following cavernous nerve injury
- 2012
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 1476-5489 .- 0955-9930. ; 24:2, s. 84-90
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Tidskriftsartikel (refereegranskat)abstract
- In an effort to identify neuronal repair mechanisms of the major pelvic ganglion (MPG), we evaluated changes in the expression of nestin, an intermediate filament protein and neural stem cell marker following cavernous nerve crush injury (CNI). We utilized two groups of Sprague Dawley rats: (i) sham and (ii) bilateral CNI. Erectile responses to cavernous nerve stimulation (CNS) were determined at 48h in a subset of rats. The MPG was isolated and removed at 48h after CNI, and nestin immunolocalization, protein levels and RNA expression were evaluated. At 48 h, erectile responses to CNS in CNI rats were substantially reduced (P<0.05; similar to 70% decrease in intra-cavernous pressure/mean arterial pressure) compared with sham surgery controls. This coincided with a dramatic 10-fold increase (P<0.05) in nestin messenger RNA expression and protein levels in the MPG of rats with CNI. Immunoflourescence microscopy demonstrated that nestin upregulation after CNI occurred within the ganglion cell bodies and nerve fibers of the MPG. In conclusion, CNI induces nestin in the MPG. These data suggest that nestin may be involved in the regenerative process of the cavernous nerve following crush injury. International Journal of Impotence Research (2012) 24, 84-90; doi:10.1038/ijir.2011.50; published online 13 October 2011
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| 15. |
- Scorolli, C, et al.
(författare)
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Relative prevalence of different fetishes
- 2007
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Ingår i: International journal of impotence research. - : Springer Science and Business Media LLC. - 0955-9930 .- 1476-5489. ; 19, s. 432-437
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to estimate the relative frequency of Fetishes in a large sample of individuals. Using the Internet as a data source, we examined 381 discussion groups. We estimate, very conservatively, that at least 5000 individuals were targeted. The relative frequency of each preference category was estimated considering (a) the number of groups devoted to the category, (b) the number of individuals participating in the groups and (c) the number of messages exchanged. The three measures agree both parametrically (Cronbach's α=0.91) and non-parametrically (Kendall's W=0.94, P<0.01). Preferences for body parts or features and for objects usually associated with the body were most common (33 and 30%, respectively), followed by preferences for other people's behavior (18%), own behavior (7%), social behavior (7%) and objects unrelated to the body (5%). Feet and objects associated with feet were the most common target of preferences. These findings provide the first large database in an area, where the knowledge is particularly scarce.
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| 16. |
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| 17. |
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| 18. |
- Ueckert, S., et al.
(författare)
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Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5)
- 2011
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 1476-5489 .- 0955-9930. ; 23:5, s. 206-212
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Tidskriftsartikel (refereegranskat)abstract
- The clitoris contributes to the normal female sexual response cycle. A significance of cyclic guanosine monophosphate (GMP) has been assumed in the control of clitoral vascular smooth muscle. As only a few investigations on the physiology of the vascular and non-vascular clitoral tissue have been carried out, knowledge on the mechanisms controlling this particular female genital organ is still vague. It has been suggested that human clitoral corpus cavernosum smooth muscle is regulated by nitric oxide (NO)/cyclic GMP and related key enzymes, such as NO synthases (NOSs) and the phosphodiesterase type 5 (PDE5). The present study evaluated in the human clitoris, by means of immunohistochemistry, the expression and distribution of key enzymes of the cyclic GMP pathway, such as the endothelial NOS, PDE2, PDE11 and cyclic GMP-dependent protein kinase type I (cGKI) in relation to the PDE5. Immunohistochemistry revealed the presence of PDE2, PDE5 and cGKI in the smooth muscle wall of blood vessels transversing the supepithelial and stromal space. Immunosignals specific for PDE2 were also identified in interstitial-like cells located in the basal epithelial layer. Staining for PDE11A was observed in single nerve trunks located in the clitoral stroma. The results are in favor of a role of the cyclic GMP signaling in the control of clitoral blood flow. It seems likely that PDE2 and PDE11 are also involved in the mechanism of local (neuro) transmission in the clitoris. International Journal of Impotence Research (2011) 23, 206-212; doi:10.1038/ijir.2011.29; published online 23 June 2011
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| 19. |
- Ueckert, S., et al.
(författare)
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Expression and distribution of the transient receptor potential cationic channel A1 (TRPA1) in the human clitoris-comparison to male penile erectile tissue
- 2017
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Ingår i: International journal of impotence research. - : NATURE PUBLISHING GROUP. - 0955-9930 .- 1476-5489. ; 29:5, s. 179-183
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Tidskriftsartikel (refereegranskat)abstract
- The transient receptor potential cationic channel ankyrin 1 (TRPA1) is a channel protein assumed to act in various human tissues as mechano- and pain sensor and play a role in neurotransmission. The expression of TRPA has already been investigated in the human prostate and urethra, however, only very few studies have addressed the expression and distribution in the male and female genital tract. The present study aimed to investigate by means of immunohistochemistry (double-labeling technique, laser fluorescence microscopy) in the human clitoris and penile erectile tissue the localization of TRPA1 in relation to nNOS, the vasoactive intestinal polypeptide (VIP) and vesicular acetylcholine transporter (VAChT). In the clitoral tissue, TRPA1 was observed in basal epithelial cells and slender nNOS-positive nerve fibers transversing the subepithelial space. To a certain degree, in the clitoral epithelial cells, TRPA1 was found co-localized with vimentin. In human corpus cavernosum, immunoreactivity for TRPA1 was seen in nerves transversing the cavernous sinusoidal space and running alongside small arteries, these nerves also displayed expression of the vesicular acetylcholine transporter protein (VAChT). Varicose nerves containing nNOS or VIP were not immunoreactive for TRPA1. It seems likely that TRPA1 is involved in nitric oxide-mediated afferent sensory transmission in the clitoris while, in penile erectile tissue, a role for TRPA1 in cholinergic signaling might be assumed.
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| 20. |
- Ueckert, S., et al.
(författare)
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Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human vagina
- 2015
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Ingår i: International journal of impotence research. - : Nature Publishing Group: Open Access Hybrid Model Option B. - 0955-9930 .- 1476-5489. ; 27:1, s. 16-19
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Tidskriftsartikel (refereegranskat)abstract
- The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract While the expression of TRPA1 has been investigated in a variety of tissues, up until today no Study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue, Reverse transcriptase PCR (RT-PCR) Was applied in order to identify messenger ribonuleic acid specifically encoding for TAPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of imnnunohistocheitical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal Wall and epithelium Immunostaining related to TRPA1 was observed in the basal epithelium and in slender Varicose nerve fibers transversing the subepithelial and stromal space of the Vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP The Smooth:musculature of the vaginal wall, and small vessels interspersing the tissue did not present Signals related to TRPA1, The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.
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| 21. |
- Ueckert, S., et al.
(författare)
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Protein kinase enzymes in the human vagina-relation to key mediators of the cyclic AMP and cyclic GMP pathways
- 2017
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Ingår i: International journal of impotence research. - : NATURE PUBLISHING GROUP. - 0955-9930 .- 1476-5489. ; 29:4, s. 127-131
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Tidskriftsartikel (refereegranskat)abstract
- Aside from phosphodiesterase (PDE) isoenzymes,,protein kinases (cAK=cyclic AMP-binding protein kinase, CGK=cyclic GMP-binding protein kinase) have also been identified as important receptors for cyclic nucleotides. A significance of protein kinases in the control of the function of the male and female reproductive tract has been suggested; however,up until today, only a few approaches have addressed these enzymes in female genital tissues: The present study aimed to investigate by means of biochemical and immunohistochemical methods the expression of cAK and cGK. The distribution of cAK(I) and cGK(I) in relation to the vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and PDE type 4 (PDE4) was also evaluated. Cytosolic supernatants prepared from specimens of vaginal wall smooth muscle or epithelium were subjected to anion exchange chromatography and the activities of cAK and cGK(I) measured. To evaluate the distribution of cAK(I) and cGK(I) in relation to VIP, CGRP and PDE4, immunohistochemistry was conducted in sections of the human vaginal wall (full-wall specimens). Activities representing cGK(I) and cAK(I) were resolved from the chromatography column. Staining specific for cAK(la) was identified in both vascular and non-vascular vaginal smooth musculature, immunoreactivity for cGK(113) was observed in the smooth muscle and endothelium of small arteries interspersing the sections. cAK(I alpha)-positive vessels were found innervated by slender varicose nerve fibers presenting the expression of VIP and CGRP. These arteries also expressed PDE4. Localization of cAK and cGK in close relation to key mediators of the cyclic AMP (PDE4, VIP) and cyclic GMP (CGRP) pathways indicate that both signaling systems may synergistically work together in human vaginal tissue.
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