SS-penogram: a new diagnostic test for Erectile Dysfunction.

The clinical reports on Sildenafil Citrate (Viagra) are mainly based on individual observations. However, there is a paucity of objective studies in the literature. In order to objectively examine the effect of Sildenafil, a SS (Sexual Stimulation)-Penogram that is a non-invasive, simple and physiologic method was developed using a radioisotope (RI). One hundred and four SS-penograms were performed on patients who had a documented Erectile Dysfunction (ED) lasting for more than 6 months. After an intravenous injection of 99mTc-RBC (15 mCi), the first penogram was taken immediately after sexual stimulation, which was done by 30 minutes of erotic videotape viewing. Forty minutes after administering 25 to 100 mg of Sildenafil, a second penogram was taken. The characteristics of each penogram were analyzed according to a previously reported method. The results were graded as follows; Type I(normal function; 5 min or more of peak erectile response with an induction period of 1 to 6 min), Type II-A (impossible function type; i.e., showing less than 2 times the basal radioactivity level), Type II-B (the unstable type; showing less than 5 min of peak erectile response), and Type II-C (the delayed type; which showed a delay of more than 15 min after the start of sexual stimulation). The patients were grouped according to their response afterSildenafil Citrate (Viagra) administration, and the effect ofSildenafil Citrate (Viagra) was assessed by comparing the radioactivity from between 7 to 22 minutes and the changes in the characteristics of the penogram. The mean age of the patients was 44.9 +/- 10.2 (23 - 68) years. In the first penogram, Type I was found in 12 patients, and Type II-A in 14, Type II-B in 73, Type II-C in 1 and a mixed (II-B + C) type was found in 4 patients. A second penogram afterSildenafil Citrate (Viagra) administration, showed Type I in 46 patients, and Type II-A in 10, Type II-B in 46 and a mixed type was found in 2 patients. The responses afterSildenafil Citrate (Viagra) were categorized as follows: 1) An excellent response group (consisting of 56 patients-53.9%); Those who showed greater than 50% increase in the RI area afterSildenafil Citrate (Viagra) treatment. 2) A good response group consisting of (23 patients-22.1%); i.e., those who showed a less than 50% but greater than a 20% increase in the RI area afterSildenafil Citrate (Viagra) administration. 3) A borderline group (consisting of 15 patients-14.4%); showing less than a 20% change in the RI area afterSildenafil Citrate (Viagra) treatment. 4) non-response group (consisting of 10 patients-9.6%). The therapeutic efficacy of Sildenafil, as determined by the SS-penograms, revealed that there was an augmentation in the erectile capabilities in 76% of men (79/104) but a non-response was observed in 9.6% (10/104). The efficacy ofSildenafil Citrate (Viagra) on the SS-penogram did not correlate with the patient's age (p=0.198). It is believed that the SS-penogram can be used to accurately evaluate the natural erectile status in sexual and pharmacological stimulation, and provides the most objective erectile response in any therapeutic trial. Consequently, the primary challenge for any Erectile Dysfunction remedy is to be able to demonstrate its efficacy. A further evaluation is warranted in the non-response group, which was not based on any severe organic dysfunction

Patterns of use ofSildenafil Citrate (Viagra) among commercially insured adults in the United States: 1998-2002.

Sildenafil is increasingly being marketed to younger healthcare consumers. The purpose of this study was to profileSildenafil Citrate (Viagra) use in commercially insured, adult beneficiaries. Annual ambulatory prescription claims data from 1998 to 2002, for a nationwide, random sample of over 5 million life-years of commercially insured adults (aged > or =18 y), were examined retrospectively. The overall prevalence ofSildenafil Citrate (Viagra) use increased from 0.8% (1998) to 1.4% (2002), an 84% increase. While the growth in use slowed in older males, use became more pronounced in younger males and females and decreased in older females. The fastest growing segment of users was found to be males aged 18-45 y. The proportion of users who had two or more claims for a medication that is suspected of inducing Erectile Dysfunction (ED) and/or a marker for a suspected ED-inducing disease decreased over the study period. Our findings suggest that use may increase among younger male and female patients and those without an underlying etiologic reason for use

Interactions between cGMP- and cAMP-pathways are involved in the regulation of penile smooth muscle tone.

Nitric oxide (NO)/cyclic GMP (cGMP)-mediated mechanisms have a pivotal function in reducing the tone of the penile smooth musculature during normal erectile responses. The cyclic AMP (cAMP) signaling pathway is also involved in the adjustment of smooth muscle contractility, and suggestions for interactions between cGMP- and cAMP-mediated mechanisms have been presented. Using activators of the cGMP- or the cAMP-pathway, as well as inhibitors of protein kinase A (PKA; cAMP-dependent kinase) and protein kinase G (PKG; cGMP-dependent kinase), the present study was undertaken to further delineate the functional relation between these pathways in the penis. In addition, the distribution of PKA and some cAMP-binding phosphodiesterases (cAMP-PDEs) were investigated in human erectile tissue. Functional experiments were performed on isolated human corpus cavernosum (HCC). The effects of an inhibitor of the PKA, Rp-8CPT-cAMPS (10 microM), or the PKG, Rp-8-pCPT-cGMPS (10 microM), on relaxation induced by the cumulative administration of sodium nitroprusside (SNP), forskolin,Sildenafil Citrate (Viagra) or tadalafil (IC351) were studied in preparations of HCC precontracted with 1 microM norepinephrine (NE). Using immunohistochemical procedures, the presence of immunoreactivity for cAMP-PDEs PDE3, PDE4, and PDE4A, as well as for PKA was investigated in specimens of HCC from which preparations were also used in the functional experiments. Forskolin, SNP, sildenafil, and IC 351 dose-dependently reversed NE-induced tension of isolated HCC preparations. The relaxing effects of SNP were significantly attenuated by Rp-8-pCPT-cGMPS, but not by Rp-8CPT-cAMPS. In contrast, relaxation induced by forskolin,Sildenafil Citrate (Viagra) and tadalafil were significantly reversed by both Rp-8-pCPT-cGMPS and Rp-8CPT-cAMPS. Abundant immunoreactivity for PDE3 and PKA was observed in the corpus cavernosum smooth muscle cells. Immunoreactivity for PDE4 was also detected in the smooth musculature and in the cytoplasm of endothelial cells lining the cavernous sinusoids, as well as in nerve fibres interspersing the trabecular stroma. The present results support the hypothesis of interactions between cGMP- and cAMP-mediated signals in the HCC, and suggest that the effects of inhibitors of PDE5 on isolated erectile tissue may also partly or indirectly include actions of the cAMP second messenger system. The exact mechanism by which such an interaction occurs is not clear, but it may involve altered activity of the cGMP-inhibited PDE3 brought about by a change in the intracellular levels of cGMP by the inhibition of PDE5. This will in turn lead to increasing levels of cAMP, facilitating the interaction of cAMP with the PKA. The immunoreactivity specific for PDE3, PDE4, PDE4A and PKA registered in HCC section is also in support of an important role for the cAMP/PKA-system for penile smooth muscle function

Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva.

The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline andSildenafil Citrate (Viagra) were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mg/kg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mg/kg) andSildenafil Citrate (Viagra) (5 mg/kg) prevented cadmium-induced oxidative stress in saliva. Theophylline andSildenafil Citrate (Viagra) inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors

Synthesis and phosphodiesterase inhibitory activity of newSildenafil Citrate (Viagra) analogues containing a carboxylic acid group in the 5'-sulfonamide moiety of a phenyl ring.

NewSildenafil Citrate (Viagra) analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) thanSildenafil Citrate (Viagra) by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations

Management of Erectile Dysfunction by combination therapy with testosterone andSildenafil Citrate (Viagra) in recipients of high-dose therapy for haematological malignancies.

Erectile Dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg ofSildenafil Citrate (Viagra) orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant

Effect ofSildenafil Citrate (Viagra) on anxiety in the plus-maze test in mice.

Several studies have shown a role of nitric oxide/cyclic guanosine monophosphate signaling pathway in the regulation of anxiety. The effects of the phosphodiesterase (PDE) 5 inhibitors on anxiety are not fully understood. The aim of present study was to investigate the possible role of sildenafil, an inhibitor of cyclic GMP-specific phosphodiesterase, on anxiety in the plus-maze test in mice.Sildenafil Citrate (Viagra) at a dose of 0.5 mg/kg had no significant effect on the behavior in the plus-maze test but at doses of 1 and 3 mg/kg induced an anxiogenic effect. The combination ofSildenafil Citrate (Viagra) (1 mg/kg, i.p.) and methylene blue (1 mg/kg, i.p.) abolished the anxiogenic-like effect of sildenafil. The combination ofSildenafil Citrate (Viagra) (1 mg/kg, i.p.) and L-arginine (50 mg/kg, i.p.) decreased the percentage of time spent in open arms compared to saline-treated group. Diazepam at a dose of 2 mg/kg significantly increased the percentage of time spent in open arms (p < 0.05).Sildenafil Citrate (Viagra) at a dose of 3 mg/kg and the combination of L-arginine (50 mg/kg, i.p.) andSildenafil Citrate (Viagra) (1 mg/kg, i.p.) significantly decreased the locomotor activity (p < 0.05). These results suggest that a nitric oxide-cGMP pathway seems to play an important role in sildenafil-induced anxiogenic-like effect

IsSildenafil Citrate (Viagra) failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP.

Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) Erectile Dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of Erectile Dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whetherSildenafil Citrate (Viagra) failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting withSildenafil Citrate (Viagra) refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease.Sildenafil Citrate (Viagra) refractory Erectile Dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency