Single Ion Pair Is Essential for Stabilizing SHP2's Open Conformation.

Src-homology-2-domain-containing PTP-2 (SHP2) is a widely expressed signaling enzyme whose misregulation is associated with multiple human pathologies. SHP2's enzymatic activity is controlled by a conformational equilibrium between its autoinhibited ("closed") state and its activated ("open") state. Although SHP2's closed state has been extensively characterized, the putative structure of its open form has only been revealed in the context of a highly activated mutant (E76K), and no systematic studies of the biochemical determinants of SHP2's open-state stabilization have been reported. To identify amino-acid interactions that are critical for stabilizing SHP2's active state, we carried out a mutagenic study of residues that lie at potentially important interdomain interfaces of the open conformation. The open/closed equilibria of the mutants were evaluated, and we identified several interactions that contribute to the stabilization of SHP2's open state. In particular, our findings establish that an ion pair between glutamate 249 on SHP2's PTP domain and arginine 111 on an interdomain loop is the key determinant of SHP2's open-state stabilization. Mutations that disrupt the R111/E249 ion pair substantially shift SHP2's open/closed equilibrium to the closed state, even compared to wild-type SHP2's basal-state equilibrium, which strongly favors the closed state. To the best of our knowledge, the ion-pair variants uncovered in this study are the first known SHP2 mutants in which autoinhibition is augmented with respect to the wild-type protein. Such "hyperinhibited" mutants may provide useful tools for signaling studies that investigate the connections between SHP2 inhibition and the suppression of human disease progression.

In vitro mitochondrial apoptosis of melanoma cells via immature Poncirus trifoliata fruit extract.

OBJECTIVE: Poncirus trifoliata (P. trifoliata) fruits exert phytotherapeutic effects, depending on their maturity level. However, the mechanism by which these phytotherapeutic effects are exerted remains undefined - especially in cancers. Therefore, in this study, we investigated the effects of the immature fruit extract of P. trifoliata on a B16 melanoma cell line. MATERIALS AND METHODS: The effect of immature P. trifoliata extract on B16 cells was evaluated by MTT assay, cell proliferation, FACScan analysis of cell cycles, confocal imaging analysis, nuclear (Hoechst) staining, apoptosis assay (Annexin V-fluorescein isothiocyanate/propidium iodide staining), and Western blot assay. The capacity of immature P. trifoliata extract to inhibit the invasion and migration of B16 cells was assessed using the scratch-wound assay and Matrigel migration assay. The effect of immature P. trifoliata extract on mitochondrial function was determined via the mitochondrial membrane potential assay, activity, and fraction and cytosol proteins. RESULTS: Treating B16 cells with a methanol extract of immature P. trifoliata (MEPT) significantly inhibited cell viability, migration, and invasiveness in a dose- (p<0.01) and time (p<0.01)- dependent manner. MEPT arrested the cells in the G1 phase of the cell cycle and led to the activation of the PI3K/AKT/p21 pathway. Furthermore, MEPT dose-dependently induced apoptosis in B16 cells by increasing the expression of the pro-apoptotic proteins Bax and Apaf-1, while decreasing the expression of the anti-apoptotic protein, Bcl-2. MEPT treatment also decreased mitochondrial membrane potential. CONCLUSIONS: Immature P. trifoliata extract inhibited the growth of melanoma cells by inducing cell apoptosis through mitochondrial pathways. Therefore, further research into immature P. trifoliata extract as a potential therapeutic compound for melanoma treatment is warranted.

The immunoregulatory effect of co-3 polyunsaturated fatty acids on lymphocyte in cGVH mice / 中国药理学通报

Aim To investigate the effect of dietary intake of o)-3 poly unsaturated fatty acids ( u>-3 PUFAs) on the immune function of chronic graft versus host disease (cGVH) lupus model mice.Methods A single intraperitoneal injection of bml2 mice lymphocytes was used to establish a cGVH mouse model.On the day of modeling, 90% cd-3 PUFAs and 97% EPA were given by gavage for 14 days.The immune indexes of mice were evaluated by flow cytometry, and the serum total J J J ∗ IgG levels were measured by ELISA.Results Compared with control group, cGVH group significantly down-regulated Treg subsets, and up-regulated the Tfh , GC B and plasma subsets in the lupus mice.Comparer] with model control group, u>-3 PUFAs could significantly elevate Treg subsets, and decrease TFH, (X] B, and plasma subsets; serum total IgG levels in the 97% EPA group were significantly reduced.Conclusion In the cGVH lupus mouse model, co-3 PUFAs can suppress some immune functions by increasing Treg cells, reducing TFH, GC B, plasma cells and inhibiting the secretion of IgG.Such immunomodulatory effect provides new sights into the development of a potentially novel treatment modality for cGVH.

Short communication: Dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.

Effect of the Lactobacillus rhamnosus strain GG and tagatose as a synbiotic combination in a dextran sulfate sodium-induced colitis murine model.

Synbiotics, a combination of prebiotics and probiotics, produce synergistic effects to promote gastrointestinal health. Herein, we investigated the synbiotic interaction between the Lactobacillus rhamnosus strain GG (LGG; a probiotic strain) and tagatose (a prebiotic) in a dextran sulfate sodium (DSS)-induced colitis murine model. Initially, body weight, food intake, and clinical features were dramatically decreased after treatment with DSS, and the addition of LGG, tagatose, or both ameliorated these effects. In our pyrosequencing analysis of fecal microbiota, DSS treatment increased the abundance of Proteobacteria and decreased that of Firmicutes. When LGG and tagatose were administered as synbiotics, the gut microbiota composition recovered from the dysbiosis caused by DSS treatment. In particular, the abundance of Bacteroides, Lactobacillus, and Akkermansia was significantly associated with probiotic, prebiotic, and synbiotic treatments. Taken together, our results suggest that LGG and tagatose as synbiotics can alleviate colitis, and synbiotics could be applied as dietary supplements in dairy foods such as yogurt and cheese.

Review of Vertebral Augmentation: An Updated Meta-analysis of the Effectiveness.

BACKGROUND: To update vertebral augmentation literature by comparing outcomes between vertebroplasty (VP), balloon kyphoplasty (BKP), vertebral augmentation with implant (VAI), and nonsurgical management (NSM) for treating vertebral compression fractures (VCFs). METHODS: A PubMed literature search was conducted with keywords kyphoplasty, vertebroplasty, vertebral body stent, and vertebral augmentation AND implant for English-language articles from February 1, 2011, to November 22, 2016. Among the results, 25 met the inclusion criteria for the meta-analysis. Inclusion criteria were prospective comparative studies for mid-/lower-thoracic and lumbar VCFs enrolling at least 20 patients. Exclusion criteria included studies that were single arm, systematic reviews and meta-analyses, traumatic nonosteoporotic or cancer-related fractures, lack of clinical outcomes, or non-Level I and non-Level II studies. Standardized mean difference between baseline and end point for each outcome was calculated, and treatment groups were pooled using random effects meta-analysis. RESULTS: Visual analog scale pain reduction for BKP and VP was -4.05 and -3.88, respectively. VP was better than but not significantly different from NSM (-2.66), yet BKP showed significant improvement from both NSM and VAI (-2.77). The Oswestry Disability Index reduction for BKP showed a significant improvement over VAI (P < .001). There was no significant difference in changes between BKP and VP for anterior (P = .226) and posterior (P = .293) vertebral height restoration. There was no significant difference in subsequent fractures following BKP (32.7%; 95% confidence interval [CI]: 8.8%-56.6%) or VP (28.3%; 95% CI: 7.0%-49.7%) compared with NSM (15.9%; 95% CI: 5.2%-26.6%). CONCLUSIONS/LEVEL OF EVIDENCE: Based on Level I and II studies, BKP had significantly better and VP tended to have better pain reduction compared with NSM. BKP tended to have better height restoration than VP. Additionally, BKP had significant improvements in pain reduction and disability score as compared with VAI. CLINICAL RELEVANCE: This meta-analysis serves to further define and support the safety and efficacy of vertebral augmentation.

Baseline and postfusion opioid burden for patients with low back pain.

OBJECTIVES: To evaluate opioid usage patterns for patients with low back pain (LBP) with and without spinal fusion surgery (fusion patients and nonfusion patients, respectively), including long-term prescriptions post fusion. STUDY DESIGN: Claims data of outpatient pharmaceutical prescriptions from privately insured patients. METHODS: The 3-year utilization, cost, and morphine milligram equivalents (MME) of opioid prescriptions were evaluated for patients with LBP with and without lumbar fusion. For fusion patients, opioid prescriptions before and after fusion, as well as prescription use 3, 6, and 12 months following fusion surgery, were analyzed. RESULTS: Thirty-one percent of patients with LBP had opioid prescriptions within the first 6 months of initial diagnosis, which increased to 42.1% within 3 years. More than twice as many fusion patients as nonfusion patients filled opioid prescriptions (87.2% vs 41.5%; P <.001). Fusion patients had 62% and 48% more days with opioid dosages of at least 50 and at least 90 MME/day, respectively, than nonfusion patients (≥50 MME/day, 84 days vs 52 days; ≥90 MME/day, 50 days vs 34 days; both P <.001). Opioid burden was greater for fusion patients following surgery. Fusion patients continued to have 2 months' supply with at least 50 MME/day and 1 month's supply with at least 90 MME/day at least 12 months following surgery. CONCLUSIONS: The opioid burden in the LBP population is high and is further elevated in those who subsequently undergo fusion surgery. Long-term opioid prescriptions persisted in 27% of fusion patients 12 months post surgery. Efforts to identify efficacious alternative therapies to treat LBP may reduce the societal burden of chronic opioid use.

Expression of sodium/iodide transporters and thyroid stimulating hormone receptors in thyroid cancer patients and its correlation with iodine nutrition status and pathology.

OBJECTIVE: To investigate the relationship between the expression of sodium/iodide transporter (NIS) and thyroid stimulating hormone receptor (TSHR) and iodine nutritional status in patients with thyroid carcinoma. PATIENTS AND METHODS: 146 cases of thyroid cancer in Shanghai Gongli Hospital, the Second Military Medical University between February and December 2014 were selected as thyroid cancer group, 120 cases of normal thyroid morphology examined by thyroid ultrasound at the same period were selected as normal group. General information and thyroid function of two groups were recorded and analyzed. H&E staining was used to perform histopathological study on both normal group and thyroid cancer group, and immunohistochemistry was used to detect NIS and TSHR protein expression and position. Reverse transcriptase polymerase chain reaction (RT-PCR) was used for quantitative detection of NIS and TSHR mRNA in the two groups, and the relationship between iodine nutrition and NIS and TSHR expression in thyroid cancer patients was studied. The expression of NIS and TSHR in each group was detected by Western blotting, and the difference in NIS and TSHR expression was analyzed by SPSS 17.0 statistical software. RESULTS: The difference of serum total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH) levels between the normal group and the thyroid cancer group was statistically significant (p < 0.05). H&E staining showed that the histopathology of the thyroid cancer group was significantly different from that of the normal group. Immunohistochemistry showed the positive expression of NIS and TSHR in thyroid cancer group. The expression of NIS and TSHR mRNA and protein in thyroid cancer patients was significantly lower than that in normal group detected by RT-PCR and Western blotting. Analysis of variance showed that the difference of NIS and TSHR expression between the two groups was statistically significant (p < 0.05). CONCLUSIONS: These findings indicated that the expression of NIS and TSHR in thyroid cancer is closely related to iodine nutritional status, which has important research value.

Anti-inflammatory character of Phelligridin D modulates periodontal regeneration in lipopolysaccharide-induced human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Phelligridin D is a hispidin analogue from the mushroom Phellinus baumii that is widely used as a food source in East Asia. This study tested phelligridin D for the anti-inflammatory effect and mechanism in lipopolysaccharide (LPS)-induced human periodontal ligament cells (HPDLCs). The objective of this study was to clarify whether the anti-inflammatory function of phelligridin D affects periodontal regeneration for supporting the HPDLCs of teeth. MATERIAL AND METHODS: Primary HPDLCs were isolated from healthy teeth and then cultured. The anti-inflammatory function, mechanism and differentiation molecules were verified with reactive oxygen species generation and western blot analysis in LPS-induced HPDLCs. RESULTS: HPDLCs showed increased inflammatory molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1) and decreased osteogenic proteins (bone morphogenetic protein-7, Osterix and runt-related transcription factor 2) by LPS treatment. Phelligridin D decreased inflammatory molecules and increased osteogenic molecules via downregulation of the extracellular signal-regulated kinase and c-jun N-terminal kinases pathway among the mitogen-activated protein kinase, followed by blocking of nuclear factor kappa-B translocation from cytosol to nucleus. In addition, phelligridin D showed antioxidant properties by reducing reactive oxygen species activity. Finally, the anti-inflammatory and antioxidant function of phelligridin D promoted the periodontal differentiation of HPDLCs. CONCLUSION: These results suggest that phelligridin D supports teeth on the alveolar bone against outside stress, and may be used as an anti-inflammatory compound for the prevention of periodontitis or periodontal regenerative related disease.

Correction to: Polymyxin B causes DNA damage in HK-2 cells and mice.

In the original publication of the article, part of Fig. 6 is missing. The missing subpanels, Fig. 6c, d are given below.

Polymyxin B causes DNA damage in HK-2 cells and mice.

Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 µM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0.05). Time-course studies were performed using a mouse nephrotoxicity model (cumulative 72 mg/kg). Kidneys were collected over 48 h and investigated for histopathology and DNA damage. Notable increases in γH2AX foci (indicative of double-stranded breaks) were observed in both cell culture (up to ~ 44% cells with 5+ foci at 24 h, p < 0.05) and mice treated with polymyxin B (up to ~ 25%, p < 0.05). Consistent with these results, in vitro assays showed high binding affinity of polymyxin B to DNA. Together, our results indicate that polymyxin B nephrotoxicity is associated with DNA damage, leading to chromosome missegregation and genome instability. This novel mechanistic information may lead to new strategies to overcome the nephrotoxicity of this important last-line class of antibiotics.

Relationships between 25(OH)D concentration, sarcopenia and HOMA-IR in postmenopausal Korean women.

OBJECTIVE: Sarcopenia and insulin resistance are common co-morbidities in the elderly and are known to be associated with vitamin D deficiency. However, no previous studies have investigated interactions between all three of these factors. We aimed to investigate the relationship between 25-hydroxyvitamin D concentration, sarcopenia, and insulin resistance in postmenopausal Korean women. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey 2008-2011. Participants were 3744 postmenopausal Korean women. Sarcopenia was defined as appendicular skeletal muscle mass divided by body weight >1 standard deviation below the mean for women aged 20-40 years. The serum 25-hydroxyvitamin D and fasting insulin levels were measured, and insulin resistance was calculated using the formula: fasting plasma glucose (mg/dl) × fasting insulin (mIU/l)/405. RESULTS: We found a strong inverse association between 25-hydroxyvitamin D concentration and sarcopenia in postmenopausal Korean women (p = 0.0009). There was also a significant association between sarcopenia and insulin resistance, independent of vitamin D and obesity status (p < 0.0001). However, there was no significant association between 25-hydroxyvitamin D concentration and insulin resistance. In the subgroup analysis, insulin resistance was found to be determined by sarcopenic rather than vitamin D status. CONCLUSIONS: Sarcopenia was associated with both insulin resistance and 25-hydroxyvitamin D concentration in postmenopausal Korean women, regardless of obesity status. However, 25-hydroxyvitamin D concentration was not associated with insulin resistance. Sarcopenia is therefore of greater clinical importance due to its close relationship with insulin resistance.

Cellular Assays for Evaluating Calcium-Dependent Translocation of cPLA2α to Membrane.

The group IVA phospholipase A2, commonly called cytosolic phospholipase A2α (cPLA2α), is a widely expressed enzyme that hydrolyzes membrane phospholipid to produce arachidonic acid and lysophospholipids, which are precursors for a number of bioactive lipid mediators. Arachidonic acid is metabolized through the cyclooxygenase and lipoxygenase pathways for production of prostaglandins and leukotrienes that regulate normal physiological processes and contribute to disease pathogenesis. cPLA2α is composed of an N-terminal C2 domain and a C-terminal catalytic domain that contains the Ser-Asp catalytic dyad. The catalytic domain contains phosphorylation sites and basic residues that regulate the catalytic activity of cPLA2α. In response to cell stimulation, cPLA2α is rapidly activated by posttranslational mechanisms including increases in intracellular calcium and phosphorylation by mitogen-activated protein kinases. In resting cells, cPLA2α is localized in the cytosol but translocates to membrane including the Golgi, endoplasmic reticulum, and the peri-nuclear membrane in response to increases in intracellular calcium. Calcium binds to the C2 domain, which promotes the interaction of cPLA2α with membrane through hydrophobic interactions. In this chapter, we describe assays used to study the calcium-dependent translocation of cPLA2α to membrane, a regulatory step necessary for access to phospholipid and release of arachidonic acid.

Impact of opportunistic salpingectomy on anti-Müllerian hormone in patients undergoing laparoscopic hysterectomy: a multicentre randomised controlled trial.

OBJECTIVE: The aim of the study was to investigate whether opportunistic salpingectomy has any deleterious effects on ovarian reserve and increases surgical risk in patients undergoing laparoscopic hysterectomy. DESIGN: A multicentre, randomised controlled trial. SETTING: Three university hospitals in Korea. POPULATION: Sixty-eight patients undergoing laparoscopic hysterectomy for the treatment of symptomatic benign uterine diseases. METHODS: Patients were randomised to undergo either opportunistic salpingectomy (n = 34) or no salpingectomy (n = 34) during laparoscopic hysterectomy. MAIN OUTCOME MEASUREMENTS: The primary and secondary outcome measures were the change of ovarian reserve, determined by the rate of decline in anti-Müllerian hormone (AMH) level from before surgery to 3 months post-surgery and surgical outcomes, respectively. RESULTS: Baseline demographic and clinical characteristics were similar between the two groups. There was also no difference in operative outcomes such as operative time, operative bleeding, or complications between the two groups. In both groups, postoperative AMH levels were significantly lower than preoperative AMH levels (both, P < 0.01). The decline rate in AMH was 12.5% (interquartile range 0.8-60.9%) in the opportunistic salpingectomy group and 10.8% (interquartile range 6.9-27.4%) in the no salpingectomy group, with no significant difference between both groups (P = 0.898). CONCLUSIONS: Opportunistic salpingectomy at the time of laparoscopic hysterectomy did not have any negative effects on ovarian reserve or increased surgical risk. TWEETABLE ABSTRACT: Opportunistic salpingectomy did not have any negative effects on ovarian reserve or increased surgical risk.

Associations of dietary calcium intake with metabolic syndrome and bone mineral density among the Korean population: KNHANES 2008-2011.

Excessive amount of calcium intake increased risk for metabolic syndrome in men. However, modest amount decreased the risk of metabolic syndrome and osteoporosis in postmenopausal women. Modest amount of calcium also increased bone mineral density (BMD) in both men and postmenopausal women. INTRODUCTION: The present study aimed to evaluate the associations of dietary calcium intake with metabolic syndrome and bone mineral density (BMD) in Korean men and women, especially postmenopausal women. METHODS: The study was performed using data from the Korean National Health and Nutrition Examination Survey (2008-2011) and included 14,705 participants (5953 men, 4258 premenopausal women, and 4494 postmenopausal women). Clinical and other objective characteristics, presence of metabolic syndrome, and the BMD of the femur neck and lumbar spine were evaluated according to dietary calcium intake. RESULTS: There was a higher tendency for metabolic syndrome in men with a dietary calcium intake of >1200 mg/day than with ≤400 mg of calcium intake; >400 and ≤800 mg of calcium intake was helpful for postmenopausal women to decrease risk for metabolic syndrome. Overall, the group with calcium intake >400 and ≤800 mg daily had significantly increased BMD in both femoral neck and lumbar spine from both men and postmenopausal women. From both femoral neck and lumbar spine, the prevalence of osteoporosis in postmenopausal women significantly decreased in the group whose calcium intake was >400 and ≤800 mg daily. CONCLUSION: Excessive dietary calcium may increase the prevalence of metabolic syndrome in men. For postmenopausal women, calcium intake does not increase the risk of metabolic syndrome, but modest amount decreases the risk. It may increase the BMD in men and postmenopausal women, and also reduce the prevalence of both osteoporosis and metabolic syndrome in postmenopausal women.

The effect of prolonged breast-feeding on the development of postmenopausal osteoporosis in population with insufficient calcium intake and vitamin D level.

UNLABELLED: Breast-feeding affects bone metabolism and calcium homeostasis, and prolonged breast-feeding may influence the development of postmenopausal osteoporosis, particularly in highly susceptible populations. The study determined that breast-feeding may be a risk factor for postmenopausal osteoporosis, especially in people with low calcium intakes and vitamin D deficiencies. INTRODUCTION: The purpose of this study was to determine whether breast-feeding is a risk factor in the development of postmenopausal osteoporosis, especially in highly susceptible population. METHODS: The study was performed using data from the 2010 to 2011 Korea National Health and Nutrition Examination Survey, and it included 1231 postmenopausal women who were aged between 45 and 70 years. Osteoporosis was defined using the World Health Organization's T-score criteria, namely, a T-score of ≤-2.5 at the femoral neck or the lumbar spine. The patients' ages, body mass indexes, daily calcium intakes, serum vitamin D levels, exercise levels, smoking histories, and reproductive factors relating to menarche, menopause, delivery, breast-feeding, hormone treatment, and oral contraceptive use were evaluated. Comparisons between the osteoporosis and non-osteoporosis groups were undertaken using Student's t test and the chi-square test, and logistic regression models were built. RESULTS: A significant increase in the risk of osteoporosis was apparent in postmenopausal women with prolonged breast-feeding histories (≥24 months) (model 1: odds ratio [OR] = 2.489; 95 % confidence interval [CI] = 1.111 to 5.578, p = 0.027; model 2: OR = 2.503; 95 % CI = 1.118 to 5.602, p = 0.026; model 3: OR = 2.825; 95 % CI = 1.056 to 7.56, p = 0.039), particularly in those with inadequate serum vitamin D levels and calcium intakes (<800 mg/day). CONCLUSIONS: Breast-feeding seems to increase the risk of postmenopausal osteoporosis; however, its impact may not be definitive in women with sufficient vitamin D levels and calcium intakes. Therefore, sufficient calcium intakes and adequate vitamin D levels may be important to prevent osteoporosis in postmenopausal women that is derived from breast-feeding.

Use of vasopressin vs epinephrine to reduce haemorrhage during myomectomy: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness and safety of vasopressin with epinephrine for reducing blood loss during laparoscopic myomectomy. STUDY DESIGN: Sixty patients undergoing laparoscopic myomectomy were allocated at random to receive either dilute vasopressin or epinephrine into the serosal and/or overlying myometrium, and just around the myoma. The surgeon was blinded to the group allocation. Blood loss, duration of surgery, degree of surgical difficulty, postoperative pain scores and complications were compared. RESULTS: Patient characteristics (e.g. age, body mass index, demographic data), number of myomas, and location and size of the largest myoma were similar between the two study groups. There were no differences in operative blood loss, operative time, subjective surgical difficulty or postoperative pain between the two groups. Transient and non-serious increases in systolic and diastolic blood pressure and heart rate following intra-operative intramyometrial and/or perimyometrial injection of the vasoconstrictive agent only occurred in the epinephrine group, but the difference between the groups was not significant (13% vs 0%, p=0.112). No significant postoperative complications were observed in either group. CONCLUSIONS: Injection of dilute epinephrine before laparoscopic myomectomy was comparable to injection of dilute vasopressin in terms of operative blood loss, operative time, subjective surgical difficulty, postoperative pain and complications.

Role of second-look ultrasound examinations for MR-detected lesions in patients with breast cancer.

PURPOSE: To assess the clinical value of second-look ultrasound (US) examination for the evaluation of additional enhancing lesions detected on magnetic resonance (MR) imaging. MATERIALS AND METHODS: Between May 2008 and February 2011, 794 consecutive patients with histologically confirmed breast cancer underwent breast MR imaging. We included 101 patients with 132 additional enhancing breast lesions detected on MR imaging who underwent second-look US.  The imaging features and lesion category according to the Breast Imaging and Reporting and Data System (BI-RADS) were assessed with MR and US imaging, respectively. RESULTS: According to the BI-RADS system, 67 lesions (50.8 %) were classified as category 0, 33 lesions (25.0 %) as category 3, and 32 lesions (24.2 %) as category 4. Of the 67 indeterminate lesions on MR imaging, 34 (50.7 %) were demonstrated on second-look US. 11 of these 34 lesions showed suspicious sonographic features, including 1 lesion that showed malignancy (9.1 %, 1/11). Most of the suspicious lesions on MR imaging (26 of 32 BI-RADS category 4 lesions, 81.3 %) were demonstrated on second-look US, and 17 were malignant (65.4 %, 17/26). Of the 6 BI-RADS category 4 lesions without sonographic correlation, 1 was malignant (16.7 %, 1/6). CONCLUSION: Second-look US examination was useful for evaluating MR-detected lesions in patients with breast cancer.

Association of metabolic syndrome with coronary atherosclerosis in non-diabetic postmenopausal women.

OBJECTIVE: We investigated the possible association of metabolic syndrome with arterial stiffness and coronary atherosclerosis in non-diabetic, postmenopausal women. METHODS: A total of 293 non-diabetic, postmenopausal women who visited the health promotion center for a routine health check-up were included in a cross-sectional study. Arterial stiffness was measured by brachial-ankle pulse wave velocity, and coronary atherosclerosis was detected using 64-row multi-detector computed tomography. RESULTS: Women with coronary atherosclerosis had a significantly higher proportion of metabolic syndrome than those without coronary atherosclerosis. The brachial-ankle pulse wave velocity was significantly higher in women who had metabolic syndrome compared to those who had no metabolic syndrome (1567.71 ± 211.81 vs. 1336.75 ± 159.62 cm/s, p < 0.001). In addition, the brachial-ankle pulse wave velocity was shown to increase with increasing number of metabolic syndrome components (p for trend < 0.001). Metabolic syndrome was associated with increased risk of coronary atherosclerosis (adjusted odds ratio 2.38; 95% confidence interval 1.01-5.06), after adjusting for confounding factors. CONCLUSIONS: Metabolic syndrome increases the risk of coronary atherosclerosis in postmenopausal women. Increased arterial stiffness may partly explain an increased risk of coronary atherosclerosis in postmenopausal women with metabolic syndrome.