Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adrenergic regulation of lipolysis was studied, before and after 30 min of submaximal exercise, in isolated adipocytes removed from the abdominal and gluteal regions of healthy non-obese men and women. Noradrenaline-induced lipolysis was significantly enhanced in gluteal adipocytes from men but not in women after exercise. However, the pure beta-adrenergic responsiveness was equally increased in gluteal adipocytes of both sexes after exercise, as judged by the effect of isoprenaline. Furthermore, the alpha 2-adrenergic anti-lipolytic responsiveness was more apparent after exercise in females than in males thereby counter-balancing the increase in the beta-adrenergic effect in the gluteal region in the former. The increased beta-adrenergic responsiveness induced by exercise in gluteal adipocytes of males could be mimicked by agents acting at the levels of adenylate cyclase, coupling proteins, phosphodiesterase, and protein kinase and seems to be due to an adaptive enhancement at the hormone-sensitive-lipase level. There was no change in the stoichiometric properties of beta-adrenoceptors of gluteal adipocytes after exercise. Abdominal adipocytes of both sexes were four to five times more responsive to noradrenaline than gluteal ones. However, exercise induced no further enhancement of the catecholamine-stimulated lipolysis rate in fat cells from this site. Thus, the influence of exercise on catecholamine-stimulated lipolysis is regional and sex dependent. Men, but not women, have a greater ability to adapt lipolysis to increasing energy demands during exercise that are due to an acute increase in the effectiveness of the hormone-sensitive lipase complex.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adrenergic regulation of lipolysis in human fat cells during exercise. 175 92

Comparison of the parameters of Ca and Sr binding to bovine brain calmodulin with the activation of bovine brain phosphodiesterase by Ca2+ and Sr2+ at different calmodulin concentrations allows a quantitative description of the mechanism of activation of the enzyme. Equilibrium dialysis studies show that calmodulin possesses three high affinity (K'diss = 6 micoM) and one low affinity (K'diss = 200 microM) sites for Ca2+. All four sites display the same affinity for Sr2+ with K'diss = 180 microM. In the presence of calmodulin, soluble bovine brain phosphodiesterase is activated by Sr2+ to the same extent as by Ca2+. The activation of the enzyme shows the same Ca2+/Sr2+ selectivity ratio of 30 as the binding of the metal ions to calmodulin. Based on the findings that the Ca2+ or Sr2+ concentration at half-maximal activation of the enzyme depends on the concentration of calmodulin present, a quantitative analysis of activation was carried out as a function of the four calmodulin-metal complex species (CaM . Men). The data show that the activating species are CaM . Ca3, CaM . Ca4 or CaM . Sr3, CaM . Sr4. The interaction of these activating species with phosphodiesterase follows the Hill equation with a dissociation constant of 10(-9) M and a Hill coefficient of 2, irrespective of the binding characteristics of Ca2+ or Sr2+. The latter value agrees well with the fact that phosphodiesterase possesses two binding sites for calmodulin.
 ...
PMID:Regulation of brain cyclic nucleotide phosphodiesterase by calmodulin. A quantitative analysis. 625 54

Erectile dysfunction (ED) is the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. The disorder is age-associated, with estimated prevalence rates of 39% among men 40 years old and 67% among those 70 years old. ED is a common (2 to 3 million males in Italy) and multifactorial disease due to organic and/or psychological factors that strongly impair the quality of life in man. During the last decade many advances in the understanding of the pathophysiology of ED have been made and new therapeutic strategies have become available. It has been established that an insufficient production of nitric oxide by penile nerve terminals and/or vascular endothelium may result in an impaired erection or complete impotence. Nowadays, intracavernous injection of vasoactive drugs represents a standardised approach for the diagnosis and a treatment option for ED, but is not widely accepted by the patients. The possibility of treating ED with new oral agents (i.e. sildenafil, apomorphine, phentolamine) or intraurethral administration of prostaglandin-E1 made this therapy more acceptable. Vacuum erection devices and penile prostheses represent second-line treatments. Men with ED caused by endocrine disorders (i.e. hypogonadism, prolactinomas) should be treated appropriately (i.e. testosterone and dopaminergic agonists, respectively). Amongst new drugs, sildenafil is considered the most promising: it is a potent inhibitor of type-5 phosphodiesterase in the corpus cavernosum and therefore increases the penile response to sexual stimulation. Oral sildenafil (25-100 mg when needed) is an effective and well-tolerated treatment in impotent men suffering from ED of unknown etiology.
 ...
PMID:[Erectile dysfunction]. 1042 21

Advances in molecular biology and protein chemistry, along with increasing understanding of the mechanisms of penile erection, have spurred development of pharmacologic approaches to the treatment of erectile dysfunction (ED). The next generation of oral agents includes tadalafil, a potent, highly selective phosphodiesterase 5 inhibitor. In vitro studies have shown that tadalafil enhances relaxation of trabecular smooth muscle, and clinical trials have supported its efficacy and tolerability in a broad population of men with ED. The effect of tadalafil in enhancing the erectile response to sexual stimulation is relatively rapid in onset and lasts for >or=24 hours. The ability of patients with ED treated with tadalafil to achieve improved erectile function is demonstrated by significantly increased subjective measures of penetration ability, successful intercourse, and sexual satisfaction. Partners have expressed similar or higher levels of satisfaction with the results of treatment. Men with ED of psychogenic, organic, or mixed etiology and in a range from mild to severe have experienced significant improvment with tadalafil treatment. Response to treatment in men with diabetes has been robust and not affected by disease severity. Tadalafil has been well tolerated. Adverse events have generally been mild or moderate and have abated with continued treatment. Headache and dyspepsia have been most frequently reported. Changes in color vision have been rare (<0.1%) with tadalafil across all clinical trials. Tadalafil appears to be a safe and effective treatment for men with ED.
 ...
PMID:Efficacy and tolerability of tadalafil, a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction. 1460 20

Sexual dysfunction associated with radical retropubic prostatectomy (RRP) may start before the surgery. Men undergoing RRP frequently have some degree of sexual dysfunction. In addition to the psychological stress of the diagnosis, the biopsy may itself have a detrimental effect. After surgery, all men will experience loss of ejaculate, because the organ responsible for ejaculate has been removed. Orgasm quality is adversely affected in many men. Erectile dysfunction is immediate and recovery from it is slow. Initially, phosphodiesterase (PDE)-5 inhibitors do not work, and they take up to 18 months for their effect to be maximized. Younger men who have had bilateral nerve-sparing procedures respond the best. Combination treatment with prostaglandin E1 or high-dose PDE-5 inhibitors may provide salvage therapy when initial PDE-5 inhibitor therapy has failed.
 ...
PMID:Sexual dysfunction after radical prostatectomy. 1698 95

Perception of sexuality varies considerably from population to population and their cultural inheritance, depending on whether you consider occidental, oriental or African cultures. In a wider concept of environment, worries, anxiety or stress induced by work, family, social and economic factors may have a negative impact on sexual functions. Quantitative surveys on sexuality try to measure the incidence of love feelings on sexual behaviour but they cannot determine the close overlaps between mind and body. To give his partner satisfaction, men do not always need performing well. Men also have right to love women, their own ways and according to their means. Impotence or erectile dysfunction (ED) is nowadays a subject that is more and more studied on conceptual, epidemiological as much as clinical levels. Taking this trouble into consideration is relatively new for the general public and seems to coincide with the launching towards the end of the last decade of the first real effective oral treatment, the phosphodiesterase 5 (PDE5) inhibitors and of the communication developed around this event. Demand for sexual problems management seems to be on the increase.
 ...
PMID:[Erectile dysfunction, sexuality and sociocultural aspects]. 1714 47

Epidemiological studies have demonstrated an age-stratified increase in the incidence and prevalence of erectile dysfunction (ED). There is a greater degree of openness today when discussing sexual matters and more information on the treatment of ED is available to the public through the media. Quality-of-life issues are now a matter of great importance to the aging population. Men and their partners are no longer prepared to merely accept ED as a natural consequence of aging. The advent of a simple and effective oral therapy for ED has also indirectly fueled the increase in treatment-seeking behaviour among men. Despite great strides in research into ED, our knowledge and understanding of the pathophysiological mechanisms is still in its infancy. As a result, we are able to treat only the symptom of ED rather than prevent it. Common diseases found in the population, such as diabetes mellitus and coronary artery disease appear to be risk factors for the development of ED. Therefore, physicians need to identify any underlying co-existing organic diseases in their patients presenting with ED. Whenever possible, patients are encouraged to attend their consultation sessions with their partners because ED is a condition affecting 'the couple' and not just the man. Psychogenic aspects of ED should also be explored during the consultation. Efforts need to be made to uncover and address the presence of any psychological stressors, if necessary with the help of a psychosexual therapist. The first-line treatment of ED is oral phosphodiesterase-5 inhibitors. For those who do not respond to oral therapy, there is no defined 'step-ladder' escalation in alternative therapy. It is up to the physician to discuss the options with the patient or couple and reach a decision based on their preference.
 ...
PMID:An overview of the diagnosis and treatment of erectile dysfunction. 1718 76

Recent large-scale epidemiological studies have documented a strong association between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). This observation has two important scientific and clinical aspects: (i) to reveal the pathomechanism linking LUTS and ED and (ii) to consider this fact in the individual approach for diagnosis and management of these two disorders. The following hypotheses are under investigation to explain the relation between LUTS and ED: (i) an increased Rho-kinase activation, (ii) an alpha-adrenergic receptor imbalance, (iii) a decrease of NOS/NO in the endothelium, (iv) atherosclerosis affecting the small pelvis and (v) an autonomic hyperactivity, each affecting simultaneously bladder, prostate and penis. According to a recent randomized trial, sildenafil has a positive effect on LUTS yet not on uroflowmetry in men with LUTS and ED. Although further trials are mandatory, phosphodiesterase-5 inhibitors might play a role in the management of LUTS in the future. alpha-Blockers have no relevant effect on erectile function, tamsulosin leads to retrograde ejaculation in up to 10%. 5alpha-Reductase inhibitors are associated with ED, loss of libido and reduction of ejaculate volume in up to 10%. Transurethral and open prostatectomy induce retrograde ejaculation in up to 90% of patients while their impact on erectile function is still controversially discussed. Minimal invasive treatment options (laser prostatectomy, transurethral microwave thermotherapy) have a lower rate of retrograde ejaculation in the range of 20-70%. LUTS and ED are strongly linked although the exact mechanism is poorly understood. Men seeking for help for LUTS/benign prostatic hyperplasia should be assessed for different aspects of sexual dysfunction and informed regarding the impact of medication and surgery on sexual health.
 ...
PMID:Lower urinary tract symptoms and erectile dysfunction; links for diagnosis, management and treatment. 1761 8

In total, 1122 men completed non-validated structured interviews on sexual attitudes and on erectile dysfunction treatment expectations and barriers. Dimensions of sexual attitudes and treatment expectations and barriers were extracted by factor analysis and subjects were grouped into types by cluster analysis. Five types emerged: the sensation seeker, the sensuous, the anxious, the confident and the abstinent. The majority of men agreed on the importance of sex for the partnership. For the majority of anxious, sensuous and sensation-seeking men, sex was important for self-esteem. Expecting quality of life, enjoyment, self-esteem and hard reliable erections from treatment with phosphodiesterase-5 inhibitors, anxieties for side effects and loss of control, sexual abstinence and desire for an intensive sex life had the strongest impact on the likelihood of use. Men's sexual attitudes vary considerably and impact reactions to erection difficulties. A typology of five groups was developed, which will contribute to research on and understanding of men's sexual and treatment-seeking behaviors.
 ...
PMID:A typology of men's sexual attitudes, erectile dysfunction treatment expectations and barriers. 1771 24

Mental stress is a risk factor for cardiovascular events in men with vascular risk factors (VRFs) and is also associated with erectile dysfunction (ED), a frequent complaint of men with VRFs. The aim of this study was to investigate the effect of inhibition of phosphodiesterase-5 or of placebo in men with ED and VRFs on self-evaluated psychological distress, erectile function and quality of sexual life. Thirty-six men with ED and VRFs were randomized to 4 weeks of tadalafil (20 mg/every other day) or placebo treatment. Sexual Health Inventory for Men (SHIM), questions 1-3 of Life Satisfaction (LiSat) questionnaire, Symptom Check-List-90R, a multidimensional inventory exploring psychological dimensions were applied before and after treatment. The SHIM score improved after treatment with tadalafil compared with baseline and with placebo (F = 10.38; p = 0.0030). Sexual life satisfaction (LiSat-2) was significantly improved after tadalafil and after placebo, but a strong positive correlation was observed between LiSat-2 and SHIM score after tadalafil treatment (r = 0.59, p = 0.0003) and not after placebo (r = 0.22, p = 0.189). Psychological features were significantly changed after treatment, although a specific effect of tadalafil vs. placebo was observed only for interpersonal sensitivity (F = 4.48; p = 0.042). Obsessive-compulsive dimension, depression, anxiety, psychoticism were significantly improved in the tadalafil group and in the placebo group, although the improvement was always more relevant after treatment with tadalafil. These preliminary data suggest that a short treatment of ED reduced psychological distress and improved quality of sexual life in men with VRFs.
 ...
PMID:Treatment of erectile dysfunction reduces psychological distress. 1791 83


1 2 3 Next >>