Biomedical subjects

Emmanuele A Jannini

Publications and source records attributed to Emmanuele A Jannini.

16 recordsLinked to original sources

PubMed2006

Subcellular localization and regulation of type-1C and type-5 phosphodiesterases.

We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demonstrated for the first time that PDE5 is localized in discrete cytoplasmic foci and vesicular compartments corresponding to centrosomes. We also found that PDE5 intracellular localization is not cell- or species-specific, as it is conserved in different animal and human cells. PDE5 protein levels are strongly regulated by the mitotic activity of the smooth muscle cells (SMCs), as they were increased in quiescent, contractile myometrial cultures, and conditions in which proliferation was inhibited. In contrast, PDE1C levels decreased in all conditions that inhibited proliferation. This mirrored the enzymatic activity of both PDE5 and PDE1C. Increasing cGMP intracellular levels by dbcGMP or sildenafil treatments did not block proliferation, while dbcAMP inhibited myometrial cell proliferation. Together, these results suggest that PDE5 regulation of cGMP intracellular levels is not involved in the control of SMC cycle progression, but may represent one of the markers of the contractile phenotype.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2006

Subclinical erectile dysfunction: proposal for a novel taxonomic category in sexual medicine.

The definition of erectile dysfunction currently used and accepted worldwide does not encompass all possible changes to male erection. Partial, temporary, or episodic absence of erection is not considered as true erectile dysfunction. This leads to a lack of diagnosis and therapy and perhaps even the risk of the subsequent development of overt impotence. The lack of an evidence-based diagnosis of such a condition may be due to the widespread, pernicious self-prescription of erection drugs, obtained from the illegal market. To define the pathological condition of men experiencing a lack of erection who are unaffected by erectile dysfunction, we propose herein a new taxonomic category, based on new sexological criteria. In addition, we suggest research into biochemical markers to define this condition, which we have named subclinical erectile dysfunction.

Erectile Dysfunction↗

PubMed2005

Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients.

CONTEXT: Thyroid hormones have a dramatic effect on human behavior. However, their role on sexual behavior and performance has seldom been investigated in men. OBJECTIVE: The objective of this study was to evaluate the prevalence of sexual dysfunctions in patients with hyper- and hypothyroidism and their resolution after normalization of thyroid hormone levels. DESIGN AND SETTING: We conducted a multicenter prospective study at endocrinology and andrology clinics in university hospitals. PATIENTS: The study included 48 adult men, 34 with hyperthyroidism and 14 with hypothyroidism. MAIN OUTCOME MEASURES: Subjects were screened for hypoactive sexual desire (HSD), erectile dysfunction (ED), premature ejaculation (PE), and delayed ejaculation (DE) on presentation and 8-16 wk after recovery from the thyroid hormone disorder. RESULTS: In hyperthyroid men, HSD, DE, PE, and ED prevalence was 17.6, 2.9, 50, and 14.7%, whereas in hypothyroid men, the prevalence of HSD, DE, and ED was 64.3% and of PE was 7.1%. After thyroid hormone normalization in hyperthyroid subjects, PE prevalence fell from 50 to 15%, whereas DE was improved in half of the treated hypothyroid men. Significant changes were found in the subdomains of the International Index of Erectile Function; ejaculation latency time doubled after treatment of hyperthyroidism (from 2.4 +/- 2.1 to 4.0 +/- 2.0 min), whereas for hypothyroid men it declined significantly, from 21.8 +/- 10.9 to 7.4 +/- 7.2 (P < 0.01 for both). TSH and thyroid hormone levels normalized rapidly after treatment, and changes in circulating sex steroids partially reflected the changes in SHBG levels. CONCLUSIONS: In summary, most patients with thyroid hormone disorders experience some sexual dysfunctions, which can be reversed by normalizing thyroid hormone levels. Despite the associated changes in sex hormone levels, the high prevalence of ejaculatory disorders and their prompt reversibility suggest a direct involvement of thyroid hormones in the physiology of ejaculation.

Adrenergic beta-Antagonists↗

PubMed2005

Ejaculatory disorders: epidemiology and current approaches to definition, classification and subtyping.

Ejaculatory disorders (disorders of emission, ejaculation and orgasm) are the most frequent sexual complaint. Conventional algorithms on ejaculatory disorders are based on an organic or psychogenic dichotomy, with the latter being traditionally considered the main etiological cause. The scope of this review is to propose a new classification of ejaculatory disorders, with special emphasis on epidemiology and subtyping of the most frequent: premature ejaculation (PE). There is growing agreement on definition, diagnosis, and treatment options. In many cases, ejaculatory disorders can be classified by psycho-neuro-uro-endocrine symptoms. Epidemiological data, new classifications and subtyping, together with new diagnostic procedures and the availability of pharmacological aids, place this topic in the mainframe of sexual medicine. This will soon demolish the barriers to seeking help perceived by patients suffering ejaculatory disorders.

Ejaculation↗

PubMed2005

Regulation of phosphodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin.

OBJECTIVES: This study has a twofold aim: 1) to investigate whether protein expression and enzyme activity of phosphodiesterase 5 (PDE5) can be detected in human myometrium and undergo changes in relation to the presence of pregnancy and/or labor; 2) to evaluate whether PDE5 expression and activity in myometrial cells can be influenced by human chorionic gonadotropin (HCG). METHODS: Primary cultures of myometrial cells, obtained from non-pregnant women and from pregnant women at term, either before or during labor, were carried out in the presence of HCG or dibutyryl-cyclic AMP (db-cAMP), the non-hydrolizable analogue of cAMP. PDE5 expression in cultures of myometrial cells was detected by immunocytochemistry and western blot. PDE5 activity was detected in cell extracts by enzyme assay. RESULTS: PDE5 is expressed and is functionally active in smooth muscle cells. Treatment of cell cultures with HCG and db-cAMP results in a reduction of PDE5 expression and activity. The effects of HCG and db-cAMP are exerted irrespective of the functional status of the myometrium (non-pregnant, pregnant not in labor, pregnant in labor). CONCLUSIONS: PDE5 protein is expressed in human non-pregnant and pregnant myometrium. HCG reduces PDE5 expression and enzyme activity in smooth muscle cells, possibly through a pathway involving cAMP.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2005

Male reproductive physiology as a sexually selected handicap? Erectile dysfunction is correlated with general health and health prognosis and may have evolved as a marker of poor phenotypic quality.

Many extravagant physical traits are selected because they are used as cues for mate choice (sexual selection). Why is mate choice driven by costly ornaments? A theory of sexual selection posits that extravagant traits are preferred because are reliable indicators of superior (heritable) phenotypic quality. In particular, the preferred traits can be expressed only in individuals with superior conditions because are handicaps which impose a high cost to the carrier. The human penis achieves its reproductive function by the complex neuro-vascular mechanisms that controls erection. Surprisingly, erectile dysfunction and infertility, two condition which nearly annihilate fitness, are widespread medical conditions which affect millions of people of any age worldwide. The very high incidence of erectile dysfunction appears as an evolutionary paradox. Impotence is associated with all major systemic diseases as well depression and stress. Stress is also one of the causes of infertility. Therefore, male reproduction appears to be extremely sensitive to internal and external stressors. Moreover, erectile dysfunction is a predictor of myocardial infarction and stroke, whereas men with regular sexual activity have lower risk of death due to coronary disease. This large body of medical literature makes erection the best case for a fitness indicator in the human male. We suggest that the fragility of male sexual physiology observed in modern society is the specific consequence of an evolutionary process driven by the handicap principle.

Animals↗

PubMed2005

Epidemiology of premature ejaculation.

PURPOSE OF REVIEW: Accumulating evidence suggests that premature ejaculation is the most common sexual symptom. This review focuses on the epidemiology of premature ejaculation from geographical and medical perspectives. RECENT FINDINGS: In the past year many articles have been published using the data from the Global Study of Sexual Attitudes and Behaviors, a large survey that investigated various aspects of sex and relationships among 27 500 men and women aged 40-80 years. Despite some methodological bias, discussed herein, a prevalence of more than 21% seems a realistic figure for premature ejaculation. SUMMARY: Premature ejaculation is the most prevalent sexual dysfunction in every country.

Adolescent↗

PubMed2005

Ontogenetic profile and thyroid hormone regulation of type-1 and type-8 glucose transporters in rat Sertoli cells.

The glucose transporters (GLUTs) gene encode glycoproteins responsible for facilitating transfer of glucose across plasma membrane. In testis, different members of this family are present. In particular the main GLUT mRNA expression within the adult testis is the type 8, while type 1 is more expressed in prepubertal testis. Thyroid hormone, which receptors and function have been characterized in the testis, plays a crucial role in the cellular energetic metabolism. In fact, in the immature Sertoli cells, GLUT1 is up regulated by l-triiodothyronine (T(3)). The aim of this paper is to investigate the expression profile of GLUT1 and GLUT8 in the testis during development and in adulthood and analyse the role of T(3) on their expression. To analyse the expression of GLUT8 and GLUT1 we performed Northern blot and RT-PCR experiments in the whole testis and in Sertoli cells from rats of different ages. Treatments in vivo and in vitro with T(3) were used to study the effect of thyroid hormones on GLUT1 and GLUT8 expression. The activity of the rat GLUT1 promoter and its regulation by T(3) was studied with transient transfections in gonadal and non-gonadal cell lines and in primary Sertoli cell cultures. GLUT8 is expressed at a low level in the prepubertal testis and Sertoli cells and does not appear to be under T(3) control. GLUT1 is the predominant form in immature Sertoli cells. The effect of T(3) on its mRNA accumulation was quantified and confirmed by RT-PCR (control: 0.65 +/- 0.17; T(3): 1.23 +/- 0.04, arbitrary units, p < 0.05). However, transfection experiments showed that T(3) does not directly regulate GLUT1 promoter in any cell line tested. This is confirmed by the evidence that, upon extensive analysis, the rat GLUT1 promoter and the first intron sequence do not shows any thyroid responsive elements. Our data demonstrate that GLUT1 and GLUT8 are both expressed in prepubertal testis, but only GLUT1 is regulated by T(3). In addition, we found that the effect of T(3) cannot be attributed to its action on GLUT1 promoter.

Animals↗

PubMed2004

Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa.

By real-time RT-PCR and Western blot analysis, we found that phosphodiesterase type 5 (PDE5) mRNA and protein abundance was several fold higher in human male than in female reproductive tracts. The highest mRNA level (>1 x 10(7) molecules/microg total RNA) was detected in human corpora cavernosa (CC), where PDE5 protein was immunolocalized in both muscular and endothelial compartment. The possible role of androgens in regulating PDE5 expression was studied using a previously established rabbit model of hypogonadotropic hypogonadism. In this model, hypogonadism reduced, and testosterone (T) supplementation restored, CC PDE5 gene and protein expression. In addition, T supplementation completely rescued and even enhanced cyclic GMP conversion to metabolites, without changing IC(50) for sildenafil (IC(50) = 2.16 +/- 0.62 nm). In control CC strips, sildenafil dose-dependently increased relaxation induced by electrical field stimulation, with EC(50) = 3.42 +/- 1.7 nm. Hypogonadism reduced, and T increased, sildenafil effect on electrical field stimulation, again without changing their relative EC(50) values. CC sensitivity to the NO-donor NCX4040 was greater in hypogonadal rabbit strips than in control or T-treated counterparts. Moreover, sildenafil enhanced NCX4040 effect in eugonadal rabbit strips but not in hypogonadal ones. This suggests that androgens up-regulate PDE5 in rabbit penis. We also measured PDE5 gene expression and metabolic activity in human CC from male-to-female transsexual individuals, chronically treated with estrogens and cyproterone acetate. Comparing the observed values vs. eugonadal controls, PDE5 mRNA, protein, and functional activity were significantly reduced. In conclusion, we demonstrated, for the first time, that androgens positively regulate PDE5, thus providing a possible explanation about the highest abundance of this enzyme in male genital tract.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Treatment of sexual dysfunctions secondary to male infertility with sildenafil citrate.

With the assumption that infertility and related diagnostic and therapeutic processes are stressful, an uncontrolled pilot study was designed to evaluate the effect of sildenafil citrate on sexual compliance and reproductive outcome. A group of sexually healthy men were studied after the administration of 50 mg sildenafil before semen collection for intrauterine artificial insemination (n = 25) or planned intercourse for a postcoital test (n = 12). We demonstrated that sexual dysfunction is highly prevalent in patients undergoing diagnostic procedures for infertility, and that sildenafil is effective in reversing stress-induced transitory impotence. Furthermore, sildenafil improved some seminal parameters, such as the percentage of spermatozoa with linear progressive motility, as well as the number of spermatozoa penetrating the cervical mucus. Two pregnancies were obtained after sildenafil administration.

Adult↗

PubMed2004

A prospective, randomized study using transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease.

PURPOSE: Uncontrolled studies with intraplaque electromotive administration of verapamil and dexamethasone have demonstrated objective improvements in Peyronie's disease. We performed a prospective controlled study to assess the efficacy of intraplaque electromotive verapamil/dexamethasone vs electromotive lidocaine. MATERIALS AND METHODS: Patients with Peyronie's disease were randomized into a study group (47 patients) and a control group (49 patients). For each treatment session an electrode receptacle was sited over the plaque and filled with either 5 mg verapamil and 8 mg dexamethasone (study group) or 2% lidocaine (control group), and a 2.4 mA electric current was applied for 20 minutes. All patients were scheduled for 4 sessions per week for 6 weeks. Assessment before and after treatment included measurements of plaque volume and penile curvature, and pain on erection (from questionnaire). RESULTS: A total of 37 patients in the study group and 36 in the control group completed treatment courses. In the study group there were significant decreases in median plaque volume from 824 to 348 mm, and in penile curvature from 43 to 21 degrees. In the control group median volume and curvature were unchanged. The difference in results after treatment between the 2 groups was also significant. Significant pain relief occurred in both groups, transient in the control group and permanent in the study group. All patients experienced temporary erythema at the electrode site. There were no other side effects. CONCLUSIONS: Intraplaque electromotive verapamil and dexamethasone induce substantial objective improvement in Peyronie's disease compared to electromotive lidocaine administration.

Administration, Cutaneous↗

PubMed2004

Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels.

OBJECTIVE: Lack of sexual activity due to erectile dysfunction (ED) decreases testosterone (T) levels through a central effect on the hypothalamic-pituitary axis. In this paper we studied the effect of different type V phosphodiesterase (PDE5) inhibitor treatments for ED on the reversibility of this endocrine pattern. DESIGN: Open-label, retrospective study. PATIENTS: Seventy-four consecutive patients were treated on demand with sildenafil (Sild) (50 mg) and tadalafil (Tad) 20 mg. MEASUREMENTS: The success in sexual intercourse was recorded and total (tT) and free testosterone (fT) levels were studied before and after 3 months of treatment. RESULTS: Basal level of tT and fT were at the bottom of the normal range and LH levels were at the top of the high normal range. After treatments, this endocrine pattern was reversed in both groups. However, the T increase in Sild-treated patients was significantly lower than in those treated with Tad (4.7 +/- 2.7 vs. 5.1 +/- 0.9, P < 0.001). fT levels followed a directly proportional pattern, while the inverse was found when LH production was studied. The intercourse rate reflected this effect: in fact, the Sild group showed a 4.9 +/- 2.9/month full sexual intercourse rate while in the Tad group a significantly higher rate of sexual intercourse was found (6.9 +/- 4.6/month, P = 0.04). However, drug consumption was comparable between the groups (Sild 4.9 +/- 2.9 vs. Tad 4.4 +/- 2.8 pills/month, P = 0.72). CONCLUSIONS: As it is unlikely that the two drugs have a different direct effect on the pituitary-testis axis, this effect is probably due to the higher frequency of full sexual intercourse in the Tad-treated group, because of the drug's longer half-life.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Possible correlation between type 1 diabetes mellitus and female sexual dysfunction: case report and literature review.

INTRODUCTION: Sexual dysfunction in diabetic women has received less attention in clinical research than the sexual symptoms of diabetic men. Although conflicting results have been reported, several studies suggest an increased prevalence of deficient vaginal lubrication in women with diabetes mellitus. As support to the hypothesis of a potential diabetes-related arousal dysfunction caused by a decrease in vaginal lubrication of women with Type 1 diabetes mellitus, we describe the following case report. METHODS: A 29-year-old white woman was found with a sexual arousal disorder of sudden onset, complicated by loss of orgasm and sexual desire, in absence of any marital, relational, psychological, or gynecological cause. RESULTS: One month later she was diagnosed with severe Type 1 diabetes. With the correction of diabetes and without other treatment of the sexual dysfunction, she experienced a full recovery of her sexual complaints. CONCLUSIONS: The case illustrates the importance of being aware of female sexual dysfunction as an early symptom of diabetes mellitus and suggests that a good glycemic control would be fundamental to restore a normal sexual activity in diabetic women. It also demonstrates the need to take into account, not only in males, a sexual history in the management of diabetes mellitus.

Adult↗

PubMed2003

New perspectives in the pharmacotherapy of erectile dysfunction.

Current classification of pharmacological treatments for erectile dysfunction distinguishes between central and peripheral "initiators" and "conditioners" of erection. However, such taxonomy does not take into account the impact on the couple, the ultimate recipient of the treatment. For this reason, we propose here a new, couple-based sexological taxonomy, which divides pharmacotherapies into "harmonious" and "non-harmonious". New treatments and more effective drugs are expected in the near future because of the rapid expansion of research into erection regulation mechanisms and epidemiological studies.

Adrenergic Antagonists↗

PubMed2002

Type 5 phosphodiesterase expression in the human vagina.

OBJECTIVES: It has been demonstrated that clitoral and vaginal tissues express nitric oxide synthase isoforms in a way that parallels that of the penile corpus cavernosum. Considering the role of the vagina in the female sexual response and the anatomic connection between the clitoris and the anterosuperior vaginal wall, our aim was to study the distribution of type 5 phosphodiesterase (PDE5) in the anterosuperior wall of the human vagina. METHODS: Immunohistochemistry was performed on the vaginal tissue of 14 women obtained at autopsy and on exfoliated cells of the vaginal epithelium obtained from 5 healthy female donors. Specific antibodies against PDE5 were tested on both paraffin sections and cytologic smears. Immunoblotting experiments were performed in parallel with the same antibodies. RESULTS: The histologic analysis of human cadaveric vaginal tissue revealed that PDE5 immunoreactivity was mostly localized in the smooth muscle of vessels, forming a pseudocavernous tissue in the vaginal wall and endothelium. The Skene periurethral glands and vaginal epithelium were also positive for the antibody. The latter finding was confirmed using exfoliated cells of the vaginal epithelium harvested in vivo. CONCLUSIONS: The presence and tissue distribution of PDE5 in the human vagina suggest that the integrated system of nitric oxide synthase-PDE5 may play a physiologic role not only in the male sexual response but also in female sexual arousal.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2002

Expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, and PDGF receptor-alpha and -beta during human testicular development and disease.

Platelet-derived growth factor (PDGF) plays a critical role in regulating the development and functional control of various tissues and has been implicated in the pathogenesis of serious diseases, including cancer and atherosclerosis. Given the emerging role of PDGF in the development and function of male gonads, we compared the expression profiles of the mRNAs of the PDGF A- and B-chains and of the PDGF receptor (PDGFR) alpha- and beta-subunits in fetal and adult human testis. The immunohistochemical localization of the corresponding proteins in fetal, adult, and diseased human testicular tissues was also analyzed. PDGFs and PDGFRs mRNAs were readily detected by both Northern analysis and RT-PCR. The transcript levels were higher during 16-20 wk gestation, significantly lower at 24-28 wk, and increased in the adult. An identical pattern of protein expression was confirmed by immunohistochemistry, although the cellular localization of the PDGF system changes during postnatal development, concomitantly with the progression of spermatogenesis. In the testicular samples from patients affected by either complete aplasia of germ cells or various grades of spermatogenic arrest, the immunohistochemical localization of PDGFs and PDGFRs was different from normal, confirming a close connection between germ cells and PDGF system distribution. These results indicate that PDGF, through complex interactions, could play a leading role in ontogenesis and testicular pathophysiology in humans. Finally, the expression of PDGF ligands and receptor proteins in Leydig cell tumors suggests a relationship of the PDGF system to tumorigenesis or tumor progression in this testicular neoplasm.

Adult↗