No abstract available.
Cyclic Nucleotide Phosphodiesterases, Type 5*

Penile fracture is an injury caused by the rupture of the tunica albuginea. We report an uncommon case of penile fracture with corporeal fibrosis and erectile dysfunction in a 45-year-old man who sustained a straddle injury to the erect penis. He presented with palpable plaque in the bilateral proximal corpora cavernosa and markedly decreased erectile rigidity at the distal side of the plaque. Exploration and excision of the penile plaque were performed. The patient partially recovered erectile function after surgery and administration of phosphodiesterase-5 inhibitor.
Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Fibrosis ; Humans ; Male ; Middle Aged ; Penis ; Rupture

PURPOSE: This study was conducted to determine how treatment-emergent adverse reactions (ARs) of each of the phosphodiesterase type 5 inhibitors (PDE5Is) influenced the patient when selecting a drug. MATERIALS AND METHODS: For our study, we recruited a total of 123 patients who were suffering with erectile dysfunction and they randomly took 3 different PDE5Is (sildenafil, tadalnafil, and vardenafil), at least 4 times each and then had successful intercourse after using each PDE5I. We investigated the influence of the treatment-emergent ARs on the patients selecting a PDE5I. RESULTS: Sixty eight out of 123 patients (55.3%) showed more than one AR. Five patients (4.1%) did not select any of the PDE5Is due to their treatment-emergent ARs, and 15 patients (12.2%) did not select the PDE5Is due to the severity and/or duration of the AR. Facial flushing was the most common cause of non-selection; this was followed by headache. Fifteen patients (12.2%) selected one specific PDE5I because they experienced a less severe AR with that drug. The severity and duration of the ARs increased in the group of elderly men and the group of men who took larger doses of the drug. CONCLUSIONS: ARs had an important effect on the patients' selection of a PDE5I, although the impact was quite low compared with its overall occurrence rate. The severity and/or duration of the AR were so variable, depending on the patient, that no PDE5I was better than the others in terms of attributing the selection of a PDE5I to its reduced AR.
Adverse Drug Reaction Reporting Systems ; Aged ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Flushing ; Headache ; Humans ; Male ; Phosphodiesterase 5 Inhibitors*

PURPOSE: Combination therapy with an alpha-1-adrenergic blocker and phosphodiesterase type 5 inhibitors (PDE5Is) has shown improvements in lower urinary tract symptoms (LUTS) with negligible side effects. Nonetheless, decisive advantages in symptom improvement were insufficient, and there were no clinical differences between long- or short-acting PDE5Is in combination with combination medication. METHODS: To review the studies on alpha-1-adrenergic blocker monotherapy and combination therapy with long vs. short-acting PDE5Is in their use in LUTS and erectile dysfunction (ED). A search of the MEDLINE, Embase, Cochrane Library, and KoreaMed databases was conducted from 2000 to 2014 using combinations of the relevant terms. Among the 323 relevant references discovered, 10 were selected for meta-analysis. The data showed that 616 men received combination therapy (PDE5Is with alpha-1-adrenergic blockers) or alpha-1-adrenergic blocker monotherapy. RESULTS: Meta-analysis of the combination therapy showed it was more effective than alpha-blockers in improving symptoms, with a mean International Prostrate Symptom Score change difference of -1.93 while those of the long- vs. short-acting PDE5I were -2.12 vs. -1.70. Compared to maximum flow rate (Qmax) value with monotherapy, the Qmax increased more with the combination therapy (mean difference of 0.71) while change values were 0.14 and 1.13 for the long- and short-acting PDE5Is, respectively. Residual urine decreased more with the combination therapy than it did with alpha-1-adrenergic blocker monotherapy with a mean difference of -7.09 while the mean residual urine change values for long- vs. short-acting PDE5Is were -18.83 vs. -5.93. The International Index of Erectile Function value increased by 3.99, 2.85, and 4.85 following combination therapy, and therapy with long- and short-acting PDE5Is. CONCLUSIONS: Our meta-analysis suggests that PDE5Is can signicantly improve LUTS in men with benign prostatic hyperplasia/ED. Furthermore, combination PDE5I and alpha-1-adrenergic blocker could be a more effective treatment than alpha-1-adrenergic blocker monotherapy, and the differences between long and short-acting agents were minimal.
Cyclic Nucleotide Phosphodiesterases, Type 5* ; Erectile Dysfunction* ; Humans ; Lower Urinary Tract Symptoms* ; Male ; Phosphodiesterase 5 Inhibitors* ; Prostatic Hyperplasia

OBJECTIVESTo investigate the effects of antisense oligodeoxynucleotide(ASON) on the cyclic nucleotide monophosphates (cNMP) in smooth muscle cells of human corpus cavernosum, and provide experimental groundwork for the gene therapy of erectile dysfunction.

METHODSPDE5 gene ASON(containing exon 1) was transfected into the corpus cavernosum smooth muscle cells with the presence of liposome DOTAP. Another sense oligodeoxynucleotide(SON) and 1% of bovine serum were also transducted into the cells as controls. Two of cNMP, cAMP and cGMP, were probed and measured by ELISA at 1, 2, 4, 6, 10, 24 and 48 h after transfection.

RESULTSAfter transfection, the level of cGMP(1-6 h) in human corpus cavernosum smooth muscle cells was significantly higher than that in controls(P < 0.01).

CONCLUSIONSThe PDE5 gene ASON had been showed to manifest stimulative effect on the cGMP in smooth muscle cells of human corpus cavernosum in vitro, and it provides experimental groundwork for the gene therapy of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases ; antagonists & inhibitors ; genetics ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Humans ; Male ; Muscle, Smooth ; drug effects ; metabolism ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; Penis ; cytology

PURPOSE: To compare the safety and efficacy of tamsulosin and tamsulosin with the phosphodiesterase-5 inhibitor tadalafil in combination with prednisolone as medical expulsive therapies for lower ureteric stones. MATERIALS AND METHODS: Between July 2011 and December 2012, 62 adult patients presenting with distal ureteric stones sized 5 to 10 mm were randomized equally to treatment with tamsulosin (group A) or tamsulosin with tadalafil (group B). Therapy was given for a maximum of 6 weeks. In addition, patients in groups A and B were given 5-mg prednisolone once daily (maximum 1 week). The stone expulsion rate, time to stone expulsion, analgesic use, number of hospital visits for pain, follow-up and endoscopic treatment, and adverse effects of the drugs were noted. Statistical analyses were done by using Student t-test and chi-square test. RESULTS: There was a higher expulsion rate (83.9% in group B and 74.2% in group A) and a lower time to expulsion in both treatment groups than in historical controls used in earlier studies. However, these results were not statistically significant (p=0.349, p=0.074, respectively). Statistically significant differences were noted in hospitalization for colic and analgesic requirement, which were less in group B than in group A. There were no serious adverse events. Another important finding was improvement in erectile function in group B. CONCLUSIONS: Medical expulsive therapy for distal ureteric stones using tamsulosin and tadalafil with prednisolone is safe and efficacious. Also, the prescription of tadalafil in cases of erectile dysfunction with the development of lower ureteric stones may provide additional advantages.
Adult ; Colic ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Follow-Up Studies ; Hospitalization ; Humans ; Male ; Prednisolone* ; Prescriptions ; Ureter* ; Urinary Calculi

BACKGROUND: Cyclic guanosine monophosphate (cGMP) plays an important role in the modulation of nociception. Although local sildenafil produces antinociception, by increasing cGMP through the inhibition of phosphodiesterase 5, the effect of spinal sildenafil has not been determined. The authors evaluated the effects of intrathecal sildenafil on the nociceptive behavior evoked by formalin injection and thermal stimulation. METHODS: Lumbar intrathecal catheters were implanted into rats, with formalin and Hot-Box tests used as nociceptive models. The formalin-induced nociceptive behavior (flinching response) and withdrawal latency to radiant heat were measured, and the general behaviors also observed. RESULTS: The intrathecal administration of sildenafil produced dose-dependent suppression of the flinches in both phases in the formalin test, and increased the withdrawal latency in the Hot-Box test. No abnormal behaviors were noted. CONCLUSIONS: Sildenafil, an inhibitor of phosphodiesterase 5, is active against the nociceptive state evoked in the spinal cord by formalin and thermal stimulations. Accordingly, spinal sildenafil may be useful in the management of pain.
Animals ; Catheters ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Formaldehyde ; Guanosine Monophosphate ; Hot Temperature ; Nociception* ; Pain Measurement ; Rats* ; Spinal Cord ; Sildenafil Citrate

PURPOSE: The aim of this study was to evaluate various medical treatments for the improvement of sexual function in women with sexual dysfunction. MATERIALS AND METHODS: Forty two patients that complained of desire and arousal disorders received treatments with androgen replacement, local administration of prostaglandin E1 (PGE1), administration of apomorphine and phosphodiesterase 5 inhibitor (PDE5I), and the application of a clitoral suction device. The treatment options were applied sequentially in some case. The improvement in sexual function was evaluated with respect to sexual desire, sexual sensation, sexual excitement, vaginal lubrication, orgasm and sexual satisfaction, using the Female Sexual Function Index and a subjective assessment, during masturbation. RESULTS: Androgen replacement over a 3 month period increased the sexual desire and sexual arousal response in 35.7% (5/14) and 21.4% (3/14) of the subjects, with no side effects. The local application of PGE1 improved the vaginal lubrication in 42.8% (3/7). Apomorphine increased vaginal lubrication in 12.5% (2/16) of the subjects. PDE5I improved sexual excitement and vaginal lubrication in 26.3% (5/19) of the subjects. A clitoral suction device improved the sexual sensation in 62.5% (25/40) and vaginal lubrication in 45.0% (18/40) of the subjects. Each treatment modality was more effective in secondary than in primary female sexual dysfunction. All of these modalities tested demonstrated an improvement in at least part of the sexual response, but not in the general sexual satisfaction. CONCLUSIONS: Although no improvement in sexual satisfaction was demonstrated, further studies to develop a proper indication for each treatment modality, due to their partial effectiveness toward each sexual response are warranted. Since female sexual dysfunction is not solved with a simple treatment, various treatment modalities must be applied for a significant time period.
Alprostadil ; Androgens ; Apomorphine ; Arousal ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Female* ; Humans ; Lubrication ; Masturbation ; Orgasm ; Sensation ; Sexuality ; Suction

BACKGROUND: Intrathecal sildenafil has produced antinociception by increasing the cGMP through inhibition of phosphodiesterase 5. Spinal opioid receptor has been reported to be involved in the modulation of nociceptive transmission. The aim of this study was to examine the role of opioid receptor in the effect of sildenafil on the nociception evoked by formalin injection. METHODS: Rats were implanted with lumbar intrathecal catheters. Formalin testing was used as a nociceptive model. Formalin-induced nociceptive behavior (flinching response) was observed. To clarify the role of the opioid receptor for the analgesic action of sildenafil, naloxone was administered intrathecally 10 min before sildenafil delivery, and formalin was then injected 10 min later. RESULTS: Intrathecal sildenafil produced dose-dependent suppression of flinches in both phases during the formalin test. Intrathecal naloxone reversed the analgesic effect of sildenafil in both phases. CONCLUSIONS: Sildenafil is active against the nociceptive state that's evoked by a formalin stimulus, and the opioid receptor is involved in the analgesic action of sildenafil at thespinal level.
Analgesia ; Animals ; Catheters ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Formaldehyde ; Naloxone ; Nociception ; Pain Measurement ; Rats* ; Receptors, Opioid* ; Sildenafil Citrate

Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Responses to treatments for jackhammer esophagus have been inconsistent in previous trials, possibly due to its heterogeneous manifestation. Thus, we reviewed 10 patients diagnosed with jackhammer esophagus and compared their clinical and manometric features at baseline. Additionally, manometric and symptomatic responses after treatment with known smooth muscle relaxants, including anticholinergic drugs (cimetropium bromide and scopolamine butylbromide) and a phosphodiesterase-5 inhibitor (sildenafil) were compared. We observed two distinct subgroups in the findings: one with hypercontractility and normal distal latencies (“classic jackhammer esophagus,” n=7) and the other with hypercontractility and short distal latencies (“spastic jackhammer esophagus,” n=3). The two types also differed in their responses to medications in that symptoms improved upon treatment with an anticholinergic agent in classic jackhammer esophagus patients, while spastic jackhammer esophagus was unresponsive to both the anticholinergic drugs and the phosphodiesterase-5 inhibitor. In conclusion, hypercontractile esophagus may be a heterogeneous disease with different underlying pathophysiologies. We introduced two novel terms, “classic jackhammer esophagus” and “spastic jackhammer esophagus,” to distinguish the two types.
Classification ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Deglutition Disorders ; Esophageal Motility Disorders ; Esophagus* ; Humans ; Muscle Spasticity* ; Muscle, Smooth ; Scopolamine Hydrobromide