👤 R D Klausner

Low-intensity extracorporeal shockwave therapy (Li-ESWT) is thought to treat erectile dysfunction (ED) by stimulating neovascularization and nerve regeneration as demonstrated in animal models by histologically increased angiogenesis and neuronal-related growth factors, though corresponding human studies are limited. We hypothesized that Li-ESWT results in appreciable increases in growth factors in human tissues, and in this proof-of-concept study we aimed to determine whether markers for neovascularization and nerve regeneration can be detected in the corporal blood of men following Li-ESWT treatment. Patients were prospectively enrolled in a clinical trial of Li-ESWT for ED. Patients received 12 bi-weekly Li-ESWT treatments of 0.2 mJ/mm eNOS, nNOS, VEGF, and BDNF were detectable and demonstrated changes in cavernosal plasma samples following Li-ESWT treatment. Twenty-five patients completed all five study visits. Mean patient age was 63. Mean baseline International Index of Erectile Function-Erectile Function score prior to treatment was 14.24 (±1.21). Corporal plasma samples were analyzed for eNOS, nNOS, VEGF, and BDNF using the enzyme-linked immunosorbent assay. Levels of eNOS, nNOS, and VEGF showed an upward trend following treatment but did not reach significance. BDNF levels were noted to decrease. Corporal blood aspirates may function as surrogates for histological studies to understand effects of Li-ESWT at the tissue level in humans. To our knowledge, this is first the molecular study in human tissues to attempt to quantify neurogenesis and neovascularization in penile tissue following Li-ESWT for ED. Although our sample size is small, we believe this represents a promising first step in understanding the effect of Li-ESWT at a tissue level in men. The clinical significance of our findings is currently unknown, but markers of neovascularization and neurogenesis are detectable in corporal plasma and may change following Li-ESWT. ClinicalTrials.gov Show less

Although iron is an essential nutrient, it is also a potent cellular toxin, and the acquisition of iron is a highly regulated process in eukaryotes. In yeast, iron uptake is homeostatically regulated by the transcription factor encoded by AFT1. Expression of AFT1-1(up), a dominant mutant allele, results in inappropriately high rates of iron uptake, and AFT1-1(up) mutants grow slowly in the presence of high concentrations of iron. We present evidence that when Aft1-1(up) mutants are exposed to iron, they arrest the cell division cycle at the G1 regulatory point Start. This arrest is dependent on high-affinity iron uptake and does not require the activation of the DNA damage checkpoint governed by RAD9. The iron-induced arrest is bypassed by overexpression of a mutant G1 cyclin, cln3-2, and expression of the G1-specific cyclins Cln1 and Cln2 is reduced when yeast are exposed to increasing amounts of iron, which may account for the arrest. This reduction is not due to changes in transcription of CLN1 or CLN2, nor is it due to accelerated degradation of the protein. Instead, this reduction occurs at the level of Cln2 translation, a recently recognized locus of cell-cycle control in yeast. Show less