Effects of chronic tadalafil use on the testes and sperm parameters of old albino rats.

The use of phosphodiesterase-5 inhibitors has become the first-line treatment of erectile dysfunction nowadays. The daily application of tadalafil has become a line of treatment of other diseases such as pulmonary hypertension and cardiomyopathy. This study aimed at exploring whether the chronic use of tadalafil has an adverse effect on the testes and semen of old albino rats. Sixty male albino rats were divided into three groups. Group 1: given 2 ml saline orally for 90 days. Group 2: received tadalafil orally (1.8 mg kg(-1) day(-1) for 3 months equivalent to 20 mg day(-1) for 3 months as in human dose) and Group 3: received tadalafil orally (1.8 mg kg(-1) day(-1) for 6 months equivalent to 20 mg day(-1) for 6 months as in human dose). Animals were observed daily for signs of toxicity and mortality. Body weight and food consumption were recorded once a week. After sacrificing the animals, gross examination of the testes was performed in situ and then the epididymis was processed for the evaluation of sperm parameters and testes with other organs relative weight was calculated. Testicular histopathological examination was performed to evaluate microscopic changes in the seminiferous tubules. The mean testicular weight was significantly lower in animals of Group 3, and no significant changes were observed in Group 2. Sperm count showed a significant time-dependent decrease. Sperm motility decreased significantly in both groups with higher effect in Group 3. Incidence of abnormal forms increased in both groups (about 5 and 7 times in Group 2 and 3 respectively). Histological examination revealed mild changes in Group 2 and moderate changes in Group 3 in the form of loosely packed connective stroma around seminiferous tubules, reduction in number of spermatogenic cells with sloughing of many spermatocytes within the lumen of some tubules. Large vacuoles appeared in the tubules which contained a fewer number of sperm. Sperm bundles were degenerated in most tubules and completely absent in others. It is concluded that chronic daily use of tadalafil produces detrimental effects on the structure and function of the testes of old male albino rats which are duration dependent.

Proliferation, DNA repair and apoptosis in androgenetic alopecia.

BACKGROUND: Androgenetic alopecia is a common hair disorder, resulting from interplay of genetic, endocrine and ageing factors. Meanwhile, it is unclear if an altered degree of proliferation or increased apoptosis could contribute to its pathogenesis. OBJECTIVE: To evaluate the role of proliferation, DNA damage and apoptosis in the pathogenesis of androgenetic alopecia. METHODS: Thirty biopsies were taken from the frontal (bald) area and occipital (hairy) area of 15 male patients with androgenetic alopecia, as well as five specimens from frontal area of five age-matched controls. These specimens were used for immunohistochemical staining of cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA repair markers (XRCC1, APE1, PARP-1) as well as apoptosis regulatory protein p53. RESULTS: The frontal bald area of patients showed significantly higher levels of X-ray Cross Complementing-1 (XRCC1; P<0.001) and p53 (P<0.001) expression when compared with occipital hairy area of patients and frontal area of controls (P=0.003 and 0.04, respectively). On the other hand, there were significantly lower expression of PCNA (P<0.001) and apurinic/apyridinic endonuclease 1 (APE1; P=0.001 and 0.02) when compared with the frontal area of controls and occipital area of patients, respectively. Meanwhile, APE1 showed significant inverse correlation with p53 overexpression (P=0.03). CONCLUSION: The frontal bald area of patients with androgenetic alopecia has lower proliferation rate that result in follicular miniaturization. There is increased DNA damage that would be beyond the capacity of cells to repair in advanced cases. An alternative pathway would take place in order to eliminate the damaged cells through apoptosis.

Nonarteritic ischaemic optic neuropathy (NAION) after 36 h of intake of sildenafil citrate: first Egyptian case.

Sildenafil citrate is a selective phosphodiesterase 5 (PDE-5) inhibitor and partial phosphodiesterase 6 inhibitor prescribed for erectile dysfunction. Post-marketing case reports of nonarteritic anterior ischaemic optic neuropathy (NAION) over the past few years suggest a potential link with PDE-5 inhibitors. We report a case of a 48-year-old male patient who had acute vision loss 36 h after the intake of 50 mg sildenafil citrate. NAION occurred at a period of minimal blood level of sildenafil citrate. So, erectile dysfunction drugs must be strongly considered with NAION even though their users may have neither predisposing nor precipitating factors for NAION and even if occurring at a time of minimal blood level of these drugs.