The Outcome of Multiple Slit on Plaque with Plication Technique for the Treatment of Peyronie’s Disease

Purpose: To evaluate the postoperative outcome of the multiple slit on plaque plication technique for the treatment of Peyronie’s disease. Materials and Methods: We retrospectively evaluated 22 patients who underwent plaque incision with penile plication for the surgical treatment of Peyronie’s disease, who had failed medical treatment between 2009 and 2014. Patients were grouped by preoperative degree of penile curvature into Group I: mild (n=5, 22.7%), Group II: moderate (n=11, 50.0%), and Group III: severe (n=6, 27.3%). After a thorough review of the medical records, we evaluated (a) the correction of the curvature; (b) sexual function; and (c) any penile shortening or other complications. Results: The mean postoperative follow-up period was 39 months. Complete correction of the curvature was attained in 21 patients (95.5%). As an inevitable complication, minimal penile shortening (＜1.5 cm) was reported by 14 patients (82.4%) but did not adversely affect sexual intercourse (0%), and all patients found the extent of penile shortening to be acceptable. Nineteen patients had good erectile function (International Index of Erectile Function ＞21). The most frequent complication was subcutaneous penile edema in three patients (13.6%), which was resolved within about 3 months following surgery. Conclusions: As a modified technique, multiple slit on plaque with plication is a simple, minimally-invasive and effective technique for correcting penile curvature regardless of curvature severity. The degree of penile curvature does not significantly predict the amount of penile length loss

The Efficacy of Medical Treatment of Peyronie’s Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor

Purpose: This study was designed to evaluate the efficacy of medical treatment of Peyronie’s disease. Materials and Methods: A total of 109 patients with Peyronie’s disease who had been treated from January 2011 to December 2014 were retrospectively reviewed in this study. Forty-four patients (Group 1) were treated with 12 mg of potassium para-aminobenzoate daily. Sixty-five patients (Group 2) were treated with combination therapy: tamoxifen (20 mg) and acetyl-L-carnitine (300 mg) twice daily in addition to a phosphodiesterase type 5 inhibitor. Ability to perform sexual intercourse, pain during erection, size of plaque, and penile curvature angle were assessed. Results: In Group 1, 30 of 44 patients (68.2%) discontinued treatment within 12 weeks, while 5 patients (7.7%) in Group 2 discontinued treatment. Pain during erection and plaque size were improved in both groups but showed no statistical difference due to the high dropout rate in Group 1. In both groups, penile curvature was improved, but demonstrated no statistical difference between the treatment groups. However, combination therapy demonstrated a better response rate in patients whose penile curvature angle was less than 30o (44.4% vs. 79.1%, p=0.048). The rate of successful sexual intercourse was significantly higher in Group 2 (42.8% vs. 78.3%, p=0.034). The number of patients who underwent surgical correction despite medical treatment was significantly higher in Group 1 (35.7% vs. 13.3%, p=0.048). Conclusions: Early medical combination therapy in Peyronie’s disease may present better results in patients whose curvature angle is less than 30o

<i>Loranthus tanakae</i> Franch. & Sav. Suppresses Inflammatory Response in Cigarette Smoke Condensate Exposed Bronchial Epithelial Cells and Mice

Loranthus tanakae Franch. & Sav. found in China, Japan, and Korea is traditionally used for managing arthritis and respiratory diseases. In this study, we analyzed the components of L. tanakae 70% ethanol extract (LTE) and investigated the therapeutic effects of LTE on pulmonary inflammation using cells exposed to cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) in vitro and in vivo in mice and performed a network analysis between components and genes based on a public database. We detected quercitrin, afzelin, rhamnetin 3-rhamnoside, and rhamnocitrin 3-rhamnoside in LTE, which induced a significant reduction in inflammatory mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and inflammatory cells in CSC exposed H292 cells and in mice, accompanied by a reduction in inflammatory cell infiltration into lung tissue. In addition, LTE increased translocation into the nuclei of nuclear factor erythroid-2-related factor 2 (Nrf2). By contrast, the activation of nuclear factor (NF)-κB, induced by CSC exposure, decreased after LTE application. These results were consistent with the network pharmacological analysis. In conclusion, LTE effectively attenuated pulmonary inflammation caused by CSC+LPS exposure, which was closely involved in the enhancement of Nrf2 expression and suppression of NF-κB activation. Therefore, LTE may be a potential treatment option for pulmonary inflammatory diseases including chronic obstructive pulmonary disease (COPD)

<i>Loranthus tanakae</i> Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD

Hypoxia-Inducible Factor-2α Is an Essential Catabolic Regulator of Inflammatory Rheumatoid Arthritis

<div><p>Rheumatoid arthritis (RA) is a systemic autoimmune disorder that manifests as chronic inflammation and joint tissue destruction. However, the etiology and pathogenesis of RA have not been fully elucidated. Here, we explored the role of the hypoxia-inducible factors (HIFs), HIF-1α (encoded by <i>HIF1A</i>) and HIF-2α (encoded by <i>EPAS1</i>). HIF-2α was markedly up-regulated in the intimal lining of RA synovium, whereas HIF-1α was detected in a few cells in the sublining and deep layer of RA synovium. Overexpression of HIF-2α in joint tissues caused an RA-like phenotype, whereas HIF-1α did not affect joint architecture. Moreover, a HIF-2α deficiency in mice blunted the development of experimental RA. HIF-2α was expressed mainly in fibroblast-like synoviocytes (FLS) of RA synovium and regulated their proliferation, expression of RANKL (receptor activator of nuclear factor–κB ligand) and various catabolic factors, and osteoclastogenic potential. Moreover, HIF-2α–dependent up-regulation of interleukin (IL)-6 in FLS stimulated differentiation of T_H17 cells—crucial effectors of RA pathogenesis. Additionally, in the absence of IL-6 (<i>Il6</i>^−/− mice), overexpression of HIF-2α in joint tissues did not cause an RA phenotype. Thus, our results collectively suggest that HIF-2α plays a pivotal role in the pathogenesis of RA by regulating FLS functions, independent of HIF-1α.</p></div

Local deletion of <i>Epas1</i> in joint tissues inhibits CIA.

<p><i>Epas1</i>^fl/fl mice were IA-injected with Ad-C or Ad-<i>Cre</i> (1×10⁹ PFU), immunized with type II collagen (CIA) or NI, and maintained for 3 wk. (A) HIF-2α in joint tissues was detected by immunostaining (<i>n</i> = 10). (B) Synovitis, cartilage destruction, pannus formation, and angiogenesis were detected by H&E staining, safranin-O staining, safranin-O/hematoxylin staining, and CD31 immunostaining, respectively. Representative images were obtained from more than 10 independent experiments. P, pannus. (C) Quantification of synovitis, pannus formation, blood vessels in the synovium, and Mankin score (<i>n</i>>10). Values are means ± SEM (*<i>p</i><0.0005). Scale bar, 50 µm.</p