SiHyun Cho

Clinical effects of the levonorgestrel-releasing intrauterine device in patients with adenomyosis

OBJECTIVEnThe aim of this study was to evaluate the long-term clinical effects of a levonorgestrel-releasing intrauterine device (LNG-IUD) on adenomyosis.nnnSTUDY DESIGNnA LNG-IUD was inserted into 47 patients who were diagnosed with adenomyosis. Uterine volume, uterine artery blood flow, pictorial blood loss assessment chart (PBAC) scores, and the degree of dysmenorrhea were evaluated before and 36 months after insertion of the LNG-IUD.nnnRESULTSnPain scores and PBAC scores dropped dramatically in 6 months and showed significant decrease after 36 months. A significant decrease in mean uterine volume was noted 12 months (156.85 +/- 49.79 mL to 118.64 +/- 41.36 mL; P < .001) and 24 months (128.84 +/- 48.70 mL; P < .001) after LNG-IUD insertion, but no significant differences were noted at 36 months. The mean pulsatility indices of both uterine arteries increased significantly 12 months after insertion (P = .002 for right; P = .011 for left) and decreased after 24 months without significance. Uterine volume and uterine blood flow were negatively correlated (Pearsons correlation, P < .05). Significant increase of uterine volume, pain scores, and PBAC scores were noted at 36 months compared with 12 months after insertion (P = .034, .021, and .001, respectively).nnnCONCLUSIONnFor patients with clinical diagnosis of adenomyosis, the LNG-IUD is effective for the reduction of uterine volume with improvement of vascularity and relief of symptoms. However, the efficacy of LNG-IUD on uterine volume may begin to decrease 2 years after insertion.

Induction of striatal neurogenesis enhances functional recovery in an adult animal model of neonatal hypoxic-ischemic brain injury

While intraventricular administration of epidermal growth factor (EGF) expands the proliferation of neural stem/progenitor cells in the subventricular zone (SVZ), overexpression of brain-derived neurotrophic factor (BDNF) is particularly effective in enhancing striatal neurogenesis. We assessed the induction of striatal neurogenesis and consequent functional recovery after chronic infusion of BDNF and EGF in an adult animal model of neonatal hypoxic-ischemic (HI) brain injury. Permanent brain damage was induced in CD-1 (ICR) mice (P7) by applying the ligation of unilateral carotid artery and hypoxic condition. At 6 weeks of age, the mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments into the ventricle: BDNF, EGF, BDNF/EGF, or phosphate buffered saline (PBS). Two weeks after treatment, immunohistochemical analysis revealed an increase in the number of BrdU(+) cells in the SVZ and striata of BDNF/EGF-treated mice. The number of new neurons co-stained with BrdU and betaIII-tubulin was also significantly increased in the neostriata of BDNF/EGF-treated mice, compared with PBS group. In addition, the newly generated cells were expressed as migrating neuroblasts labeled with PSA-NCAM or doublecortin in the SVZ and the ventricular side of neostriata. The new striatal neurons were also differentiated as mature neurons co-labeled with BrdU(+)/NeuN(+). When evaluated post-surgical 8 weeks, BDNF/EGF-treated mice exhibited significantly longer rotarod latencies at constant speed (48 rpm) and under accelerating condition (4-80 rpm), relative to PBS and untreated controls. In the forelimb-use asymmetry test, BDNF/EGF-treated mice showed significant improvement in the use of the contralateral forelimb. In contrast, this BDNF/EGF-associated functional recovery was abolished in mice receiving a co-infusion of 2% cytosine-b-d-arabinofuranoside (Ara-C), a mitotic inhibitor. Induction of striatal neurogenesis by the intraventricular administration of BDNF and EGF promoted functional recovery in an adult animal model of neonatal HI brain injury. The effect of Ara-C to completely block functional recovery indicates that the effect may be the result of newly generated neurons. Therefore, this treatment may offer a promising strategy for the restoration of motor function for adults with cerebral palsy (CP).

Bone mineral density, arterial stiffness, and coronary atherosclerosis in healthy postmenopausal women.

Objective: The aim of this study was to assess the correlation between bone mineral density (BMD), arterial stiffness, and coronary atherosclerosis in healthy postmenopausal women. Methods: We performed a retrospective review of 152 postmenopausal women who visited the health promotion center for a routine checkup, after excluding participants who had factors affecting BMD and coronary artery disease. BMD was evaluated by dual-energy x-ray absorptiometry in the lumbar spine and femur. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), and coronary atherosclerosis was assessed by 64-row multidetector computed tomography. Results: Women with osteoporosis had a significantly higher baPWV than those in the osteopenia and normal BMD groups. Higher baPWV was also associated with the presence of atherosclerosis. The baPWV was significantly positively correlated with age, systolic blood pressure, diastolic blood pressure, and neutrophil to lymphocyte ratio and negatively correlated with femur BMD. The optimum predictive value of baPWV in coronary atherosclerosis was estimated using the receiver operating characteristic curve. A cutoff of 1,506 cm/second would give a sensitivity of 83.3% and specificity of 82.9%. A higher overall risk for coronary atherosclerosis emerges with higher baPWV levels (>1,500 cm/s) after controlling for age and cardiovascular risk factors. Conclusions: Arterial stiffness by measuring baPWV can be a useful independent predictor for coronary atherosclerosis. In addition, our results suggest that postmenopausal women with osteoporosis should be considered for further evaluation of coronary atherosclerosis.

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

BACKGROUNDnRecently, 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.nnnMETHODSnUrine 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).nnnRESULTSnTwenty-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.nnnCONCLUSIONSnUrinary 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.

Neutrophil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis of endometriosis

OBJECTIVEnTo investigate the clinical value of differential white blood cell counts and neutrophil-to-lymphocyte ratio (NLR), by themselves or as adjunct to CA-125, in the diagnosis of endometriosis.nnnDESIGNnRetrospective study.nnnSETTINGnUniversity Medical Center.nnnPATIENT(S)nTwo hundred thirty-one patients with endometriosis, 145 patients with benign ovarian tumors, and 384 healthy controls participated in this study.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nSensitivities and specificities of differential white blood cell (WBC) counts, NLR, serum CA-125, and the combined marker (NLR and serum CA-125) were evaluated by receiver-operating characteristic (ROC) analysis.nnnRESULT(S)nThe mean NLR and the combined marker in patients with endometriosis were significantly higher than those in patients without endometriosis. The NLR was able to discriminate patients with endometriosis from those with benign ovarian tumors and from healthy controls, and 25 of the 38 endometriosis patients (65.8%) with minimal-to-mild disease exceeded the cutoff value. The combined marker had a sensitivity of 69.3% and specificity of 83.9% with a cutoff value of 55.7, showing 13.5% increase in sensitivity but 8.9% decrease in specificity when compared with serum CA-125 at a cutoff level of 35 IU/mL. The elevated combined marker detected 16 patients with endometriosis (42.1%) with minimal-to-mild disease, whereas only 10 patients (26.3%) had their serum CA-125 levels at more than 35 IU/mL.nnnCONCLUSION(S)nMeasurement of NLR and the combined marker may be used as simple and easily obtained diagnostic markers for endometriosis.

Expression of Cyclooxygenase-2 in Eutopic Endometrium and Ovarian Endometriotic Tissue in Women with Severe Endometriosis

Background/Aims: The purpose of this study is to evaluate the level and pattern of cyclooxygenase-2 (Cox-2) expression in endometriosis and to investigate the correlation between the expression of Cox-2 and several clinicosurgical parameters. Methods: Twenty-six patients with endometriosis and 21 patients with other benign gynecological conditions were enrolled. The eutopic endometrium was sampled by pipelle, and fragments of ovarian endometrioma and non-endometriotic ovarian cysts were sampled during surgery. Total RNA isolation and semiquantitative reverse transcriptase polymerase chain reaction was performed. Results: The expression of Cox-2 mRNA (mean ± SEM) in eutopic endometrium and ovarian endometriotic tissue significantly increased in patients with endometriosis compared with the controls. The expression of Cox-2 increased significantly in the proliferative phase in eutopic endometrium and in the secretory phase in ovarian endometriotic tissue of patients with endometriosis compared with the controls. Cox-2 mRNA expression in the endometrium and ovarian lesions significantly correlated with serum CA-125 and the diameter of the endometrioma. Conclusions: Cox-2 expression increased in the eutopic endometrium and ovarian endometriotic tissue of the patients with endometriosis. These findings indicate that Cox-2 may be involved in the pathogenesis and progression of endometriosis.

Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial.

ObjectiveThe aim of this study was to evaluate the effects of red ginseng (RG) on menopausal symptoms and cardiovascular risk factors in postmenopausal women. MethodsA randomized, placebo-controlled, double-blind clinical trial was conducted with postmenopausal women between the ages of 45 and 60 years. A total of 72 women were randomly assigned to either an RG group (supplemented with 3 g of RG, including 60 mg of ginsenosides, per day) or a placebo group for 12 weeks. We analyzed changes in menopausal symptoms (the Kupperman index and the menopause rating scale), cardiovascular risk factors (lipid profiles, high-sensitivity C-reactive protein, and carotid intima-media thickness), and serum estradiol levels from baseline to 12 weeks. ResultsSignificant improvements in the Kupperman index (P = 0.032) and in the menopause rating scale (P = 0.035) scores were observed in the RG group compared with the placebo group. Total cholesterol (P = 0.009) and low-density lipoprotein cholesterol (P = 0.015) significantly decreased in the group receiving RG. The RG group also showed a significant decrease in carotid intima-media thickness (P = 0.049). Serum estradiol levels were not influenced by RG supplementation. ConclusionsRG could be an attractive herbal dietary supplement for relieving menopausal symptoms and conferring favorable effects on markers of cardiovascular disease in postmenopausal women.

Kisspeptin, leptin, and retinol-binding protein 4 in women with polycystic ovary syndrome.

Objectives: To compare plasma kisspeptin, serum leptin, and serum retinol-binding protein 4 (RBP4) levels in women with and without polycystic ovary syndrome (PCOS) and to correlate these among each other and with clinical, hormonal, and metabolic parameters. Methods: Ninety women, including 54 women with PCOS and 36 without PCOS, participated in this study. For all patients, history and physical examinations were performed and blood samples were collected between days 3 and 8 of a spontaneous bleeding episode in the PCOS group and during normal menses of controls. Plasma kisspeptin, serum leptin, and serum RBP4 levels were measured using specific commercial assays. Results: Kisspeptin, leptin, and RBP4 levels were significantly higher in the PCOS group than in controls. Kisspeptin and RBP4 levels were significantly higher among obese PCOS patients than controls. Leptin levels were higher among obese PCOS patients than non-obese PCOS patients or controls. Kisspeptin and leptin levels of PCOS patients were significantly correlated with RBP4 levels. When only obese PCOS patients were analyzed, kisspeptin levels correlated with only the free androgen index. Conclusions: These findings suggest that kisspeptin, leptin, and RBP4 are associated with metabolic disturbances in women with PCOS.

Expression of vascular endothelial growth factor (VEGF) and its soluble receptor-1 in endometriosis

The aim of this study is to evaluate the expression of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) in peritoneal fluid (PF), peritoneal endometriotic lesions and eutopic endometrial tissues of patients with endometriosis. Peritoneal fluid, peritoneal endometriotic lesions and eutopic endometrial samples from patients with endometriosis, and peritoneal fluid, peritoneal tissue and endometrial samples from patients without endometriosis were obtained during an operative laparoscopy. The mean PF concentrations of VEGF and sFlt-1 were significantly higher in patients with endometriosis than in the controls. In the peritoneal tissue, the expressions of VEGF and sFlt-1 were significantly higher, where the expression of sFlt-1 in endometrium was significantly lower in patients with endometriosis. These findings indicate that not only abnormal expressions of angiogenic factors, but also aberrant expressions of antiangiogenic factors in the peritoneal and endometrial environment seem to be involved in the pathogenesis of endometriosis.

Concomitant increase in muscle strength and bone mineral density with decreasing IL-6 levels after combination therapy with alendronate and calcitriol in postmenopausal women.

ObjectiveThe aims of this study were to assess changes in muscle mass and strength according to changes in bone mineral density (BMD) after alendronate-calcitriol therapy and to assess subsequent changes in common biomarkers for osteoporosis and sarcopenia to establish a common strategy against these coexisting conditions. MethodsThirty-eight women with osteopenia and without conditions affecting calcium metabolism, inflammatory cytokines, acute and chronic medical conditions, and regular endurance exercise completed the study. Appendicular lean mass and BMD were measured, and relative skeletal mass index was determined. Grip strength was measured with a JAMAR hand dynamometer. Serum interleukin-6 (IL-6), protein carbonyl, and parathyroid hormone (PTH) were measured as biomarkers related to bone and muscle mass before and after a 6-month combination therapy with alendronate (5 mg) and calcitriol (0.5 &mgr;g). ResultsBaseline serum IL-6 showed significant negative correlations with lumbar BMD and handgrip strength (r = −0.458, P = 0.01, and left hand; r = −0.387, P = 0.03, respectively), whereas serum 25-hydroxy vitamin D level was 13.97 (5.65) ng/mL, compatible with vitamin D insufficiency and inversely correlated with PTH level (r = −0.481, P = 0.005). The observation of secondary hyperparathyroidism in association with 25-hydroxy vitamin D deficiency was absent, in contrast with previous reports. After treatment, the mean IL-6 level decreased by 56.5% (8.9%) (P = 0.0032), lumbar BMD increased by 2.62% (2.87%; P = 0.0002), and average handgrip strength increased by 33.52% (8.34%; P = 0.0001). Posttherapy IL-6 level was not significantly correlated with posttherapy BMD and handgrip strength (r = 0.06, P = 0.76, and r = 0.156, P = 0.45, respectively). However, the degree of IL-6 changed by treatment displayed a significant negative correlation with initial lumbar BMD and a positive correlation with PTH levels. ConclusionsImprovement not only in lumbar BMD but also in handgrip strength (a representative parameter for sarcopenia) has been observed with 6 months of alendronate-calcitriol combination therapy. Initial IL-6 levels display an inverse relationship with pretreatment lumbar BMD and handgrip strength. The degree of change in IL-6 levels induced by the combination therapy is correlated with the initial degree of the catabolic status of the bone, indicated by markers such as PTH and the severity of lumbar BMD derangements.