OBJECTIVETo investigate the ultrasonographic indexes in the evaluation of complete penile erection after oral administration of sildenafil citrate in men with normal erectile function.

METHODSThe subjects lay supine, with the penis raised upwards, its back clinging to the abdomen. The probe was placed at the base of the ventral side of the penis for longitudinal and transverse section scanning. Observations were made on the corpus cavernosum, deep artery and deep dorsal vein of the penis at the time of flaccidity and complete erection after oral administration of sildenafil citrate, respectively.

RESULTSThe examinations were acceptable to all the subjects both physically and psychologically, and all were completed successfully with no complications. Compared with the flaccid state of the penis, obvious changes were observed in the state of complete erection, including marked increases in the diameter of the corpus cavernosum ([18.57 +/- 2.50] mm, increased by [106.8 +/- 62.1]%), the inside diameter of the deep artery ([1.18 +/- 0.26] mm, increased by [54.9 +/- 29.0]%), the peak systolic velocity ([32.5 +/- 10.7] cm/s, increased by [209.3 +/- 112.9]%), and the systolic acceleration ([5.71 +/- 2.71] cm/s2, increased by [179.3 +/- 138.2]%).

CONCLUSIONOral administration of sildenafil citrate followed by ultrasonography is a new approach to the objective evaluation of penile erection, characterized by convenience, safety, non-invasiveness, non-complication, easy acceptability and easy clinical application.

Adult ; Humans ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; diagnostic imaging ; Piperazines ; pharmacology ; Purines ; pharmacology ; Sildenafil Citrate ; Sulfones ; pharmacology ; Ultrasonography

OBJECTIVETo evaluate the efficacy of sildenafil on nocturnal penile tumescence (NPT).

METHODSThirty-five patients with erectile dysfunction (ED), 28 cases of organic ED and 7 cases of psychogenic ED, were treated with sildenafil 100 mg before bedtime. The NPT of the patients was observed by using NEVA.

RESULTSErectile function significantly improved in the 28 cases of organic ED (P < 0.05), but not in the 7 cases of psychogenic ED (P > 0.05).

CONCLUSIONSildenafil can improve NPT of organic ED patients without sexual stimulation.

Adult ; Erectile Dysfunction ; drug therapy ; physiopathology ; Humans ; Male ; Middle Aged ; Penile Erection ; drug effects ; Phosphodiesterase Inhibitors ; pharmacology ; Piperazines ; pharmacology ; Purines ; pharmacology ; Sildenafil Citrate ; Sulfones ; pharmacology

In order to study the effect of phytohormone on growth and isoflavones contents of Pueraria phaseoloides hairy roots, we cultured the hairy roots with different concentrations of 6-benzylaminopurine (6-BA) alone or in combination with α-naphthaleneacetic acid (NAA). Then we determined the effects of 6-BA alone or in combination with NAA on the growth and the contents of isoflavones compounds and levels of antioxidase activities of hairy roots by spectrophotometry. The results show that 6-BA inhibited the growth, and decreased biomass and total isoflavones compounds of P. phaseoloides hairy roots. Furthermore, the inhibition was increased with the concentrations of 6-BA. Compared with the controls, different concentrations of 6-BA in combination with NAA 2.0 mg/L could inhibit the growth of hairy roots and decrease the content of total isoflavone compounds, and also significantly enhanced the contents of soluble protein and levels of peroxidase (POD) activities, but decreased the activities of superoxide dismutase (SOD). DNA ladders detected by agarose gel electrophoresis can be observed after hairy roots of P. phaseoloides were cultured with 6-BA alone for 30 days, but can appear on the 20th day after culture with 6-BA in combination with NAA 2.0 mg/L. This result indicates that 6-BA or 6-BA in combination with NAA can both stimulate appearance of programmed cell death (PCD), and NAA may play a synergistic role on PCD.
Benzyl Compounds ; Isoflavones ; chemistry ; Kinetin ; pharmacology ; Naphthaleneacetic Acids ; pharmacology ; Plant Growth Regulators ; pharmacology ; Plant Roots ; chemistry ; drug effects ; growth & development ; Pueraria ; drug effects ; growth & development ; Purines

OBJECTIVETo investigate the protective effects of sildenafil to noise-induced hearing loss in guinea pigs.

METHODSGuinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, with 10 in each group. One week after the exposure of 110 dB (A) white noise, sildenafil [10 mg/(kg×d)] and normal saline [4 ml/(kg×d)] were injected into guinea pigs of noise plus sildenafil group (NSG) and noise plus normal saline group(NNG) respectively. One week after noise exposure to four weeks continuous administration. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise, 1, 2 and 4 weeks post-drugs. The changes of cochlea hair cells were also observed by scanning electron microscope (SEM).

RESULTSAfter noise exposure, the ABR threshold shifts in NSG were significantly fewer than that in the NNG. An average of 19.1 dB in NNG compared with 19.8 dB in NSG. Four weeks after exposure, the threshold shifts were become larger to 22.0 dB in NNG while become smaller to 4.8 dB in NSG. Compared NNG with NSG, in addition to noise exposure time point, there were statistically significant differences in the rest time points after administration of the ABR threshold (P<0.05). SEM showed that the inner and outer hair cells in NNG displayed mess, fusion and imperfections. In NSG, the hair cells displayed slight pathological changes, there was no significant difference when compared with control group.

CONCLUSIONSildenafil is able to reduce the ascending of ABR thresholds shift, and it can significantly protect against noise-induced hearing loss.

Animals ; Auditory Threshold ; drug effects ; Cochlea ; drug effects ; Guinea Pigs ; Hair Cells, Auditory ; drug effects ; Hearing Loss, Noise-Induced ; physiopathology ; Piperazines ; pharmacology ; Purines ; pharmacology ; Sildenafil Citrate ; Sulfones ; pharmacology

Co-infection of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV) is not uncommon in immunocompromised hosts. Importantly, organ transplant recipients concurrently infected with HSV-1 and HCMV have a worse clinical outcome than recipients infected with a single virus. However, factors regulating the pathologic response in HSV-1, HCMV co-infected tissues are unclear. We investigated the potential biologic role of HCMV gene product immediate early 1 (IE1) protein in HSV-1-induced syncytial formation in U373MG cells. We utilized a co-infection model by infecting HSV-1 to U373MG cells constitutively expressing HCMV IE1 protein, UMG1-2. Syncytial formation was assessed by enumerating nuclei number per syncytium and number of syncytia. HSV-1-induced syncytial formation was enhanced after 24 hr in UMG1-2 cells compared with U373MG controls. The amplified phenotype in UMG1-2 cells was effectively suppressed by roscovitine in addition to inhibitors of viral replication. This is the first study to provide histological evidence of the contribution of HCMV IE1 protein to enhanced cytopathogenic responses in active HSV-1 infection.
Cell Line, Tumor ; Giant Cells/*virology ; Herpesvirus 1, Human/*growth & development ; Humans ; Immediate-Early Proteins/biosynthesis/*metabolism ; Protein Kinase Inhibitors/pharmacology ; Purines/pharmacology ; Transfection ; Virus Replication/drug effects

OBJECTIVETo obtain related pharmacodynamic data for the clinical experiment by observing the sexual activities of male rats after using sildenafil ciltrate through stomach irrigation.

METHODSForty male Sprague-Dawley rats were distributed into 4 groups with different dosages (control with distilled water, low dosage: 0.08%, medium dosage: 0.24% and high dosage: 0.72%). After the male Sprague-Dawlay rats were mated with their female counterparts in pairs, the latent period of chasing, the frequencies of chasing in 60 minutes, the latent period of intercourse and the frequencies of intercourse in 60 minutes were recorded.

RESULTSCompared with the control, the frequencies of chasing were significantly increased and the latent periods of chasing were significantly shortened in both high dosage and medium dosage groups after using sildenafil (P < 0.01); The frequencies of intercourse in 60 minutes were significantly increased and the latent periods of intercourse were significantly shortened in all the groups after the use of sildenafil.

CONCLUSIONSThe sexual activities of male rats treated with sildenafil were significantly activated.

Animals ; Dose-Response Relationship, Drug ; Male ; Phosphodiesterase Inhibitors ; pharmacology ; Piperazines ; pharmacology ; Purines ; Rats ; Rats, Sprague-Dawley ; Sexual Behavior, Animal ; drug effects ; Sildenafil Citrate ; Sulfones

AIMTo investigate a possible potentiation effect of apomorphine (APO) on sildenafil-induced penile erection in the conscious rabbit.

METHODSErection of male New Zealand White rabbits (3.5 - 4.0 kg, n=12) was assessed by measuring the length of the uncovered penile mucosa and the duration of erection before and after intravenous administration of agents. After injection of APO (0, 0.05, 0.1 and 0.4 mg/kg), sildenafil was administered intravenously in a dose-response manner (0.5, 1 and 5 mg/kg). In additional experiments, the effect of increasing doses of sildenafil in combination with APO on systemic blood pressure was evaluated.

RESULTSSystemic administration of sildenafil induced a dose-dependent increase in the penile length. Intravenous injection of APO alone did not produce any change in the penile length, while significantly enhanced the penile erection induced by sildenafil. The co-administration of 0.1 mg/kg of APO and 1 mg/kg of sildenafil was found to be the most effective combination in producing penile erection. Intravenous administration of sildenafil caused a concentration-dependent decrease in systemic blood pressure, but no additional decrease was observed with co-administration of APO.

CONCLUSIONAPO enhances the penile erection induced by sildenafil in the conscious rabbit without causing an additional decrease in blood pressure.

Animals ; Apomorphine ; pharmacology ; Blood Pressure ; drug effects ; Consciousness ; Drug Synergism ; Male ; Penile Erection ; drug effects ; physiology ; Piperazines ; pharmacology ; Purines ; Rabbits ; Sildenafil Citrate ; Sulfones

Roscovitine is a specific inhibitor of cyclin-dependent kinases (cdks) cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk5/p35. The studies on the enzyme inhibitory properties and cellular effects of roscovitine revealed that it arrests cells in G(2)/M and G(1)/S phase, inhibits the proliferation of mammalian cells and induces cell death. However, the characteristics of cell death and exact mechanism by which this cdk inhibitor kills transformed cells are unknown. We previously investigated that the roscovitine induces apoptotic death of mitotic PC12 cells. The present study was to identify whether the roscovitine-induced death is related with the specific elements of caspases in pathway of apoptosis. The morphological data of caspase-3 immunofluorocytochemistry double staining with hoechst 33342 indicated that apoptotic nuclei were identified as nuclei with chromatin condensation and nuclear fragmentation, and that caspase-3 active p17 subunit co-existed in PC12 cells treated with roscovitine 50 micromol/L for 4 h. The number of the caspase-3 positive cells increased significantly to about 42%, as compared with the normal control (P<0.001). The data of MTT assay showed that the number of viable cells treated by roscovitine (50 micromol/L) alone for 12 h was 29.03%, of the untreated controls. Both a broad-spectrum caspase inhibitor Z-VAD-FMK (50 mumol/L) and a specific caspase-3 inhibitor Z-DEVD-FMK (100 micromol/L) increased viable PC12 cells to 45.16%, (Z-DEVD-FMK) and 58.06%, (Z-VAD-FMK), respectively, in the presence of roscovitine. Non-erythroid a-spectrin is a cytoskeleted protein that is a substrate of caspase-3 cysteine proteases. To confirm the activity of caspase-3 that produced in roscovitine (50 micromol/L for 12 h)-induced PC12 cell death, activated caspase-3 specific 120 kDa spectrin breakdown products (SBDP) were detected by Western bloting using the mouse anti-non-erythroid a-spectrin monoclonal antibody. The mean relative density of bands corresponding to caspase-3 specific SBDP levels were significantly increased in the cytosolic fractions treated with roscovitine, as compared to the normal control (P<0.001). These results indicate that caspase signals, especially caspase-3 signal are necessary for the progression of proliferating PC12 cell apoptotic death evoked by roscovintine.
Animals ; Apoptosis ; drug effects ; physiology ; Caspase 3 ; physiology ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; PC12 Cells ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Rats

AIMTo examine the effect of sildenafil citrate on penile erection of male rhesus macaque.

METHODSTwenty Macaca mulatta were divided into the sildenafil treated and the control groups of 10 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined.

RESULTSThe diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group.

CONCLUSIONSildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque.

Animals ; Electromyography ; Macaca mulatta ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; anatomy & histology ; drug effects ; Piperazines ; pharmacology ; Purines ; Sildenafil Citrate ; Sulfones ; Vasodilator Agents ; pharmacology

CAL-101 is a selective inhibitor of the phosphatidylinositol-3 kinase (PI3K), it inhibits the survival, proliferation and migration of tumor cells by directly inducing apoptosis and inhibiting micro-environmental interactions. It has been determined that the P110δ isoforms of PI3K expressed primarily in cells of hematopoietic lineage, such as B and T cells. This review focuses on the target, mechanism of action, the use and prospect of CAL-101 in tumors of blood and lymph systems.
Animals ; Class Ia Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Hematologic Neoplasms ; drug therapy ; Humans ; Purines ; pharmacology ; therapeutic use ; Quinazolinones ; pharmacology ; therapeutic use ; Signal Transduction ; drug effects