Male circumcision for HIV prevention in young men in Kisumu, Kenya : a randomised controlled trial. Commentary

Activation of autocrine and paracrine signalling by endothelin 1 (ET1) binding to its receptors elicits pleiotropic effects on tumour cells and on the host microenvironment. This activation modulates cell proliferation, apoptosis, migration, epithelial-to-mesenchymal transition, chemoresistance and neovascularization, thus providing a strong rationale for targeting ET1 receptors in cancer. In this Review, we discuss the advances in our understanding of the diverse biological roles of ET1 in cancer and describe the latest preclinical and clinical progress that has been made using small-molecule antagonists of ET1 receptors that inhibit ET1-driven signalling.

Endothelin 1 in cancer: biological implications and therapeutic opportunities.

https://www.imop.gr/sites/default/files/maggi_eur_urol_2014_testosterone_ed.pdf

A Critical Analysis of the Role of Testosterone in Erectile Function: From Pathophysiology to Treatment—A Systematic Review

Background
Atrasentan is a potent, oral, selective endothelin-A (ETA) receptor antagonist with clinical activity in patients with hormone-refractory prostate cancer (HRPC). This reports the results of a Phase 3, randomized, double-blind, placebo-controlled trial of atrasentan in patients with nonmetastatic HRPC.

/pdf/phase-3-randomized-controlled-trial-of-atrasentan-in-ppbhcayyxc.pdf

Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer†‡

Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states

Study Type – Therapy (population cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

OBJECTIVE
• To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG).


PATIENTS AND METHODS
• Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months.
• Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded.
• Comparison was made between baseline and post-treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC.
• The main outcome measures were predictors of response and long-term results with long-term CC therapy in hypogonadal patients.


RESULTS
• The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL.
• Follow-up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001).
• Mean femoral neck and lumbar spine BD scores improved significantly.
• ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year.
• No adverse events were reported by any patients.


CONCLUSIONS
• Clomiphene citrate is an effective long-term therapy for HG in appropriate patients.
• The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-410X.2012.10968.x

Clomiphene citrate is safe and effective for long-term management of hypogonadism.

Cell surface biliverdin reductase mediates biliverdin-induced anti-inflammatory effects via phosphatidylinositol 3-kinase and Akt.

Complications Associated With Patient Positioning in Urologic Surgery

The impact of patient positioning can be profound. Urological surgeons must often exercise strategic positioning inorder to access retroperitoneal and pelvic organs. However, the potential for position-related morbidity, particularlyperipheral neuropraxia and compartment syndrome can be substantial. The purpose of the following review is tosummarize the current literature on positioning-related concerns as they pertain to the practicing urologist. To ourknowledge, this is the ﬁrst such review of its kind in the urological literature.

Ardavan Akhavan

Papers

Clomiphene citrate is safe and effective for long-term management of hypogonadism.

Cell surface biliverdin reductase mediates biliverdin-induced anti-inflammatory effects via phosphatidylinositol 3-kinase and Akt.

Complications Associated With Patient Positioning in Urologic Surgery

Review Article Complications Associated With Patient Positioning in Urologic Surgery

Robot-assisted extravesical ureteral reimplantation: Outcomes and conclusions from 78 ureters