tadalafil, Cialis
[Influence of gender on clinical research.]

[Article in Spanish]

Arenere Mendoza M, Cilveti Sanchez U, Idoipe Tomas A, Izuel Rami M, Navarro Aznarez H, Palomo Palomo P.

Servicio de Farmacia. Hospital Universitario Miguel Servet. Zaragoza, Spain.

Objective: To analyze clinical trials performed in our setting for the past three years from a gender-related standpoint. Material and methods: A retrospective study of 101 trials in which the pharmacy department of a 1,240-bed university hospital took part. Data sources: protocols and summary reports by the pharmacy department, Gecos(R) software program, trial follow-up cards, reception records, sample dispensation and returns, and yearly reports. Results: 17 trials included women only, 13 trials included men only, and 71 trials included patients of both genders. In female-only trials the most commonly studied condition was breast cancer (70.6%), the most common phases were phase III (47.1%) and II (41.2%) and the most commonly studied drugs were docetaxel (17.7%) and trastuzumab (11.8%). In male-only trials the most commonly studied condition was erectile dysfunction (92.3%), the most common phase was phase III (76.9%) and the most commonly studied drugs were tadalafil (38.5%) and vardenafil (30.8%). In trials without gender-related inclusion criteria the most commonly studied conditions included colon cancer (11.3%), lung cancer (11.3%), and renal failure (9.9%); the most common phase was phase III (57.7%) and the most frequently assayed drugs were interferon alpha-2a, gemcitabine and ribavirin. Overall participation rate was 62.3% for males and 37.7% for females. Conclusions: a) Regardless of gender, the most commonly studied condition was cancer, with breast cancer being most common in female-only trials and erectile dysfunction in male-only trials; b) male and female participation followed a 2:1 ratio in trials without gender-related inclusion criteria; and c) phase III was most common amongst all trials considered, with phase II having a relevant role in women-only trials as per guidelines favoring inclusion in early trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15628948&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens.

Mancina R, Filippi S, Marini M, Morelli A, Vignozzi L, Salonia A, Montorsi F, Mondaini N, Vannelli GB, Donati S, Lotti F, Forti G, Maggi M.

Andrology Unit, Department of Clinical PhysiopathologyInterdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Pharmacology and Clinical Physiopathology, Department of Anatomy, Histology and Forensic Medicine, Department of Urology, University of Florence, 50139, Florence and Department of Urology, University Vita-Salute San Raffaele, Scientific Institute H. San Raffaele, 20132 Milan, Italy.

The molecular mechanisms underlying the regulation of vas deferens (VD) motility and semen emission are still poorly understood. We now report evidence on VD expression of phosphodiesterase type 5 (PDE5), which regulates nitric oxide (NO)-induced relaxation and cGMP breakdown in smooth muscle cells. In human VD, the PDE5 abundance was relatively high (>3 x 10(6) molecules/mug total RNA), although 10-fold lower than in corpora cavernosa (CC). Also cGMP metabolising activity was higher in CC than in VD. However, both tissues share the same sensitivity to a broad panel of cGMP-related PDE inhibitors: sildenafil, tadalafil, dipyridamole, zaprinast, vinpocetine, EHNA and cilostamide. Based on the rank order of potency of these PDE inhibitors, we found that the cGMP metabolizing activity in human VD mostly corresponds to PDE5. PDE5 was immunolocalized in all the muscular layers of human and rabbit VD and was found to be negatively involved in regulating NO-induced relaxation. In addition, by using a rabbit model of hypogonadotropic hypogonadism, we found that PDE5 gene expression and activity are androgen-dependent in VD, as previously demonstrated in CC. In fact, the sensitivity to a NO-donor (NCX4040), its enhancement by PDE5 inhibitors and the PDE5-related cGMP breakdown were all affected by androgen manipulation. Our results provide a hypothesis explaining the beneficial effects of PDE inhibitors in patients with rapid ejaculation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15640438&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.

Rosano GM, Aversa A, Vitale C, Fabbri A, Fini M, Spera G.

Cardiovascular Research Unit, Department of Medical Sciences, San Raffaele--Roma, TOSINVEST SANITA', Rome, Italy.

OBJECTIVE: Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the study was to evaluate whether chronic therapy (4 weeks) with TAD improves endothelial function in patients with increased cardiovascular risk and whether this effect is sustained after discontinuation of therapy. METHODS: We randomized 32 patients with increased cardiovascular risk to receive either TAD 20 mg on alternate days or matching placebo (PLB) for 4 weeks. Patients underwent evaluation of brachial artery flow-mediated dilation (FMD), nitrite/nitrate and endothelin-1 plasma levels at baseline, at the end of treatment period and after two-weeks follow-up. RESULTS: At 4 weeks, FMD was significantly improved by TAD (from 4.2+/-3.2 to 9.3+/-3.7%, p<0.01 vs. baseline), but was not modified by PLB (from 4.1+/-2.8 to 4.0+/-3.4%, p=NS). At 6 weeks the benefit in FMD was sustained in patients that received TAD (9.1+/-3.9% vs. 4.2+/-3.2%, p=0.01 vs. baseline; 9.1+/-3.9% vs. 9.3+/-3.7%, vs. 4 weeks, p=NS) while no changes in FMD were observed in patients randomized to PLB. Also, compared to baseline, a net increase in nitrite/nitrate levels (38.2+/-12.3 vs. 52.6+/-11.7 and 51.1+/-3.1, p<0.05) and a decrease in endothelin-1 levels (3.3+/-0.9 vs. 2.9.+/-0.7 and 2.9+/-0.9, p<0.05) was found both at four and six-weeks after TAD; these changes were inversely correlated as shown by regression analysis (adjusted R2=0.81, p<0.0001). CONCLUSIONS: Chronic therapy with TAD improves endothelial function in patients with increased cardiovascular risk regardless their degree of ED. The benefit of this therapy is sustained for at least two weeks after the discontinuation of therapy. Larger studies are needed in order to assess the possible clinical implications of chronic therapy with TAD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15661417&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
From aspiration to achievement: assessment and noninvasive treatment of erectile dysfunction in aging men.

Seftel AD.

Department of Urology, University Hospital of Cleveland, Case Western Reserve University, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA. adseftel aol.com <adseftel aol.com>

More than 70% of elderly men (>or=65) remain sexually active, and more than 40%, according to one estimate, are dissatisfied with their sex lives. Declining sexual function and a reluctance to seek medical attention with advancing age are cross-cultural observations. Normal erection is largely dependent on intact function of the central and peripheral nervous systems and the penile vascular endothelium. Consequently, chronic conditions (e.g., cardiovascular disease, diabetes mellitus) and lifestyle factors (e.g., smoking) that have adverse effects on the vascular endothelium and central and peripheral nervous systems, as well as on endocrine function or connective tissues within the corpus cavernosum of the penis, can attenuate erectile function. Because of these associations, assessment of sexual function in elderly men often reveals not only erectile dysfunction (ED) but also other reversible conditions. An expanding array of noninvasive options is available to assist the clinician in individualizing ED therapy to the unique health and lifestyle needs of each elderly ED patient and his partner. These treatment alternatives include the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, and tadalafil, as well as other oral medications, such as alpha-adrenoceptor antagonists and topical vasoactive or testosterone therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15667388&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Phosphodiesterase 5 enzyme and its inhibitors: Update on pharmacological and therapeutical aspects.

Kulkarni SK, Patil CS.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. skpu yahoo.com.

Cyclic nucleotides are important secondary messengers that control many physiologic processes, including smooth muscle contractility. Phosphodiesterases (PDEs) comprise of a superfamily of metallophosphydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5' nucleotide. Currently 21 PDE genes have been cloned and are classified into 11 families (1-11) according to their sequence of homology, biochemical and pharmacological properties. Phosphodiesterase type 5 (PDE5) is one of the members of the superfamily that specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. It is composed of 875 amino acids and was first identified in lungs, vascular and tracheal smooth muscle, and platelets. PDE5 is selectively inhibited by sildenafil, vardenafil and tadalafil, and less selectively by zaprinast and dipyridamole. PDE5 inhibitors have been reported to possess antiplatelet aggregation, weak cardiac inotropic effects and vascular relaxant properties. The tissue distribution of the PDE5 family is relatively restricted compared with other PDEs. Still, recent immunohistochemical and reverse transcriptase-polymerase chain reaction analysis have demonstrated the presence of anti-PDE5 antibodies and PDE5 transcripts in rat cerebellum, kidney, pancreas, aortic smooth muscle cells, heart, placenta, skeletal muscle, and, to a much lesser extent, in other regions of the brain, liver and lungs. Research in this field is intense, with a goal of identifying and developing new, selective PDE5 inhibitors that would be beneficial in a number of maladies, as well as angina, hypertension and erectile dysfunction (ED). (c) 2004 Prous Science. All rights reserved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15672122&dopt=Abstract tadalafil Cialis