Hyo In Yang

Urinary vitamin D-binding protein is elevated in patients with endometriosis

BACKGROUND Recently, proteomic technologies have demonstrated that several proteins are differently expressed in various body fluids of patients with endometriosis compared with those without this condition. The aim of this study was to investigate proteins secreted in urine of patients with endometriosis using proteomic techniques in order to identify potential markers for the clinical diagnosis of endometriosis. METHODS Urine samples were collected from women undergoing laparoscopy for different indications including pelvic masses, pelvic pain, suspicious endometriosis, infertility and diagnostic evaluation. Proteomic techniques and mass spectrometry were used to identify proteins secreted in the urine of the patients with and without endometriosis and quantification of identified protein was performed using western blot and specific commercial sandwich enzyme-linked immunosorbent assays (ELISA). RESULTS Twenty-two protein spots were differentially expressed in the urine of patients with and without endometriosis, one of which was identified as urinary vitamin D-binding protein (VDBP). ELISA quantification of urinary VDBP corrected for creatinine expression (VDBP-Cr) revealed that urinary VDBP-Cr was significantly greater in patients with endometriosis than in those without (111.96 ± 74.59 versus 69.90 ± 43.76 ng/mg Cr, P = 0.001). VDBP-Cr had limited value as a diagnostic marker for endometriosis (Sensitivity 58%, Specificity 76%). When combined with serum CA-125 levels (the product of serum CA-125 and urinary VDBP-Cr), it did not significantly increase the diagnostic power of serum CA-125 alone. CONCLUSIONS Urinary VDBP levels are elevated in patients with endometriosis. They have limited value as a potential diagnostic biomarker for endometriosis but suggest it would be worthwhile to investigate other urinary proteins for this purpose.

Novel cosmetic patches for wrinkle improvement: retinyl retinoate- and ascorbic acid-loaded dissolving microneedles.

To evaluate wrinkle improvement and safety of a novel cosmetic dissolving microneedle patches loaded with two active compounds with different hydrophilicities, namely ascorbic acid and retinyl retinoate.

A Long-Term Treatment Outcome of Abdominal Sacrocolpopexy

Purpose The aim of this study was to evaluate the long-term treatment outcome and major complication rates of abdominal sacrocolpopexy (ASC). Materials and Methods This retrospective study included 57 Korean women who underwent ASC with mesh for symptomatic uterine or vault prolapse and attended follow-up visits for at least 5 years. Forty-seven women with urodynamic stress incontinence concomitantly received a modified Burch colposuspension. The long-term anatomical and functional outcomes and complication rates were assessed. Results The median follow-up was 66 months (range 60-108). Overall anatomical success rates (no recurrence of any prolapse ≥ stage II according to the pelvic organ prolapse-quantification system) were 86.0%. Urinary urgency and voiding dysfunction were significantly improved after surgery, however, recurrent stress urinary incontinence developed in 44.7% (21/47) of cases and half of them developed within 1-3 months post-op. Bowel function (constipation and fecal incontinence) and sexual function (sexual activity and dyspareunia) did not significantly change after surgery. Major complication requiring reoperation or intensive care developed in 12 (21.0%) cases. Conclusions ASC provides durable pelvic support, however, it may be ineffective for alleviating pelvic floor dysfunction except for urinary urgency and voiding dysfunction, and it contains major complication risk that cannot be overlooked.

Serum asymmetric dimethylarginine, apelin, and tumor necrosis factor-α levels in non-obese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with multiple risk factors for cardiovascular disease (CVD), including insulin resistance, type 2 diabetes mellitus, obesity, hypertension, and dyslipidemia. In addition, hyperandrogenism may contribute to the pathogenesis of CVD, independent of obesity and insulin resistance. We investigated serum levels of asymmetric dimethylarginine (ADMA), apelin, and tumor necrosis factor (TNF)-α as CVD risk markers and their relationship with hyperandrogenism in non-obese women with PCOS. In this study were included 82 non-obese women with PCOS and 33 controls. Women with PCOS were further divided into two groups: women with hyperandrogenism (HA-PCOS, n=37) and those without hyperandrogenism (NA-PCOS, n=45). Serum ADMA, apelin, and TNF-α levels were compared among the three groups and their relationship with hyperandrogenism was evaluated. Serum ADMA levels were significantly higher in the HA-PCOS group than in the NA-PCOS and control groups (0.45 ± 0.09 vs. 0.38 ± 0.08 vs. 0.40 ± 0.07; P<0.0005). Serum TNF-α levels were significantly higher among women with PCOS compared with controls (2.91 ± 1.25 vs. 1.74 ± 0.77; P<0.001) and in the HA-PCOS group compared with the NA-PCOS group (3.21 ± 1.24 vs. 2.60 ± 1.24; P<0.0001). Both PCOS groups had significantly lower serum apelin levels compared with controls (1.31 ± 0.54 vs. 1.16 ± 0.34 vs. 2.78 ± 1.10; P<0.0001). ADMA and TNF-α were positively correlated with total testosterone (r=0.219, P=0.022; r=0.332, P<0.001, respectively) and free androgen index (r=0.287, P=0.002; r=0.289, P=0.002, respectively), whereas apelin was negatively correlated with these parameters (r=-0.362, P<0.001; r=-0.251, P=0.008). These findings may indicate that non-obese women with PCOS are at an increased risk for CVD, which is further aggravated by hyperandrogenism.

The roles of thioredoxin and thioredoxin-binding protein-2 in endometriosis

BACKGROUND Oxidative stress is considered to be involved in the establishment and development of endometriosis. Thioredoxin (TRX) is an endogenous redox regulator that protects cells against oxidative stress, and TRX-binding protein-2 (TBP-2) is a negative regulator of TRX in the biological function and expression. The aim of this study was to investigate the roles of TRX and TBP-2 in the pathophysiology of endometriosis. METHODS A total of 35 patients with histologically confirmed endometriosis and 31 patients without endometriosis participated in this study. Real-time polymerase chain reaction was used to quantify TRX and TBP-2 mRNA levels, and immunohistochemistry (IHC) was used to assess TRX and TBP-2 protein localization in the endometrium. Serum and peritoneal fluid levels of TRX and TBP-2 were measured using a specific commercial ELISA. RESULTS There were no significant differences in TRX mRNA levels in the endometrium of patients with endometriosis and the control groups. However, TBP-2 mRNA levels in the endometrium were lower, and the TRX to TBP-2 ratio was higher in patients with endometriosis than in the control group. In particular, the TRX to TBP-2 ratio was significantly higher during late secretory and menstrual phase in patients with endometriosis compared with the control group. IHC studies also showed the decreased TBP-2 immunoreactivity in patients with endometriosis compared with the control group. There was no correlation between TRX and TBP-2 mRNA levels in patients with endometriosis, whereas TRX mRNA levels were positively correlated with TBP-2 mRNA levels in the control group. There were no significant differences between the two groups in TRX and TBP-2 levels in serum or peritoneal fluid. CONCLUSIONS Aberrant expression of TRX and TBP-2 in the endometrium may be associated with the establishment of endometriosis.

Mitochondria DNA Polymorphisms Are Associated with Susceptibility to Endometriosis

Because energy production involves oxidative phosphorylation, mitochondria are major sources of reactive oxygen species in the cell. Recent findings indicate that mitochondrial DNA (mtDNA) variants may play a role in the etiology of certain autoimmune and chronic inflammatory diseases. The aim of this study was to investigate the possible association between mtDNA polymorphisms and susceptibility to endometriosis. This study included 198 patients with histologically confirmed endometriosis and 167 patients without endometriosis as controls. Common variants of mtDNA at nt10398 (A/G transition), nt13708 (G/A transition), and nt16189 (T/C transition) were detected using polymerase chain reaction. An association study was performed with a chi-square test and logistic regression analysis. The prevalence of the mtDNA nt16189 variant was higher in patients with endometriosis (46.0%, 91 of 198) than in controls (34.7%, 58 of 167) (p=0.030) with odds ratio (OR) of 1.98 (95% confidence interval [CI]: 1.04-3.78). A combination of the 10398 and 16189 variants was also associated with increased risk for endometriosis (OR=1.90, 95% CI: 1.13-3.18, p=0.015). These associations remained significant even after adjusting for age and body mass index. Our data strongly suggest that the mtDNA 16189 variants and the combination of mtDNA 16189 and 10398 variants increase susceptibility to endometriosis.

Effects of LNG-IUS on nerve growth factor and its receptors expression in patients with adenomyosis

The levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in the treatment of dysmenorrhea associated with adenomyosis. However, the mechanism of pain relief of LNG-IUS in patients with adenomyosis is unclear. We aimed to investigate the effects of LNG-IUS on the expression of nerve growth factor (NGF) and its receptors, NGFR p75 and TrkA in patients with adenomyosis. Endometrial and myometrial tissues were prepared from 17 LNG-IUS-treated patients and 15 hormonally untreated patients who had undergone hysterectomies for adenomyosis. Immunohistochemistry with antibodies against NGF, NGFR p75, and TrkA, was performed. The expression of NGF, NGFR p75, and TrkA in endometrium and myometrium of LNG-IUS-treated patients was significantly decreased compared to those of hormonally untreated patients. Our findings may indicate that the suppression of NGF and its receptors by LNG-IUS is another possible mechanism of relieving pain in patients with adenomyosis.

Changes in Serum Levels of Cartilage Oligomeric Matrix Protein after Estrogen and Alendronate Therapy in Postmenopausal Women

Background: Cartilage oligomeric matrix protein (COMP) is a biomarker for joint destruction and its serum levels are used for assessing therapeutic efficacy. This study aims to compare changes in serum COMP levels in postmenopausal women with osteopenia/osteoporosis receiving estrogen and alendronate. Methods: A total of 62 postmenopausal women diagnosed with osteopenia or osteoporosis were treated with either estrogen (17β-estradiol 1 mg, n = 30) or bisphosphonate (alendronate 5 mg, n = 32) for 6 months. The controls were healthy postmenopausal women (n = 30). Serum COMP and osteocalcin levels were measured at baseline and after 6 months of treatment. Results: Estrogen decreased levels of COMP at 6 months compared to baseline levels (–8.35 ± 19.38%), whereas the bisphosphonate and control groups resulted in no significant changes (–5.50 ± 18.69 and –1.49 ± 25.34%, respectively). Concentrations of osteocalcin decreased significantly in both treatment groups (estrogen –25.60 ± 24.42% and alendronate –13.76 ± 23.89%, respectively). There was a significant positive correlation between changes after 6 months in COMP and osteocalcin (R = 0.48, p = 0.002). Conclusions: Postmenopausal women treated with estrogen showed significantly decreased levels of COMP after 6 months. Estrogen might provide a further treatment modality in the prevention of joint destruction.

Evaluation of the anti-wrinkle effect of an ascorbic acid-loaded dissolving microneedle patch via a double-blind, placebo-controlled clinical study.

Although an ascorbic acid‐loaded dissolving microneedle patch has been developed to improve anti‐wrinkle effects, an efficacy evaluation with a control group has not yet been performed. In this study, the anti‐wrinkle effect of an ascorbic acid‐loaded dissolving microneedle patch was evaluated in a double‐blind clinical study with a control group. In addition, a cumulative skin irritation and sensitization potential of the ascorbic acid‐loaded dissolving microneedle patch was performed.

Cyclooxygenase-2 ( COX -2) Gene-765G/C Polymorphism and Advanced-Stage Endometriosis in Korean Women

We investigated the association of COX ‐2 gene‐765G/C polymorphism and risk of advanced‐stage endometriosis in Korean women.