Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris.

The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy.

Topical calcipotriol combined with urea 20% versus intralesional injection of triamcinolone acetonide, 5-fluorouracil, and methotrexate in the treatment of nail psoriasis: A comparative study.

There is no consistently effective treatment for psoriatic nails. Topical and intralesional modalities have been recently investigated and showed promising efficacy and safety. To compare the efficacy and safety of intralesional injection of 5-fluorouracil (5-FU), methotrexate (MTX), triamcinolone acetonide (TA) versus topical calcipotriol plus urea 20% in the treatment of nail psoriasis. This study included 60 patients with nail psoriasis who were randomly assigned to 4 groups, each containing 15 patients. The first 3 groups received intralesional injection of 0.1 ml of 5-FU (group A), MTX (group B), and TA (group C) into the nail matrix and bed monthly for 3 months. Group D received a topical combination of calcipotriol/urea 20% twice daily for 3 months. Therapeutic response was assessed every month for 3 months using the target nail psoriasis severity index (NAPSI). The mean percentage of improvement was significantly higher in topical calcipotriol/urea combination (57.1 ± 26.4) than intralesional TA (44.2 ± 32.7), intralesional MTX (37.7 ± 14.2), and intralesional 5-FU (29.6 ± 14). Adverse effects were mild and insignificant in the studied groups. Topical calcipotriol/urea combination seems to be more effective and safe than intralesional injections of 5-FU, MTX, and TA.

Impact of sofosbuvir/ledipasvir versus sofosbuvir/daclatasvir regimens on the male sexual function of patients with chronic hepatitis C.

Direct-acting antivirals (DAAs) are associated with remarkable efficiency and safety profiles; however, their effect on erectile function remains insufficiently studied. This study included 200 male patients with chronic hepatitis C virus (HCV) infection divided into groups A and B and 100 healthy controls. Group A received sofosbuvir (SOF) 400 mg/ledipasvir 90 mg (Harvoni), whereas group B received SOF 400 mg/ daclatasvir 60 mg for 3 months. The Arabic version of the five-item International Index of Erectile Function-5 (IIEF-5) questionnaire was used to assess erectile function before and after completion of therapy and 3 months after. Erectile dysfunction (ED) was present in 74.5% of the patients and 14% of the controls. Immediately after treatment, group B (22.5±2.6) had a significantly higher mean IIEF-5 score than did group A (17.3±3.3) (p<0.001). Three months after treatment, all groups had no significant differences in mean IIEF-5 scores (group A: 23.1±1.9, group B: 23.3±1.9, controls: 23.7±2.3); however, free testosterone (FT) levels were significantly higher compared with pre-treatment. Both treatment regimens were associated with the improvement of erectile function and sex hormonal milieu. SOF/daclatasvir was associated with earlier improvement of erectile function compared with SOF/ledipasvir.

Seminal levels of angiotensin II and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients: Relation to fertility status.

Several theories were proposed to explain the pathophysiology of varicocele-related infertility seen in some patients. Our aim was to study the levels of angiotensin II in semen and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients in relation to their fertility status and to evaluate the influence of varicocelectomy on their levels in infertile varicocele patients. Thirty fertile and 30 infertile varicocele patients and 30 healthy controls were subjected to measurement of reproductive hormones, semen analysis, measurement of seminal angiotensin II and evaluation of angiotensin II type 2 receptor expression on spermatozoa. Infertile varicocele patients underwent varicocelectomy and were re-evaluated for the same parameters after the operation. Sperm concentration, morphology, progressive motility, seminal angiotensin II and angiotensin II type 2 receptor expression were significantly lower in infertile varicocele patients compared with the other groups. Post-operative values showed significant increase in the studied parameters compared with the pre-operative values but not to other two groups. A significant positive correlation between angiotensin II type 2 receptor expression and progressive motility was detected in all studied groups. In conclusion, dysregulation of angiotensin II and angiotensin II type 2 receptor in varicocele patients may be involved in varicocele-related infertility.