Search

Background: Endometriosis is a gynaecological disease exhibiting severe pelvic pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is known as an inflammatory mediator, and shows elevated levels in inflammatory diseases such as rheumatoid arthritis. In the present study, we evaluated whether BK is involved in endometriosis-related pain.Methods: Endometriotic lesions were used for immunohistochemistry. Primary cultures of endometriotic stromal cells (ESC) were stimulated with IL-1β and/or BK. Quantitative RT-PCR was used to evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma was measured with ELISA. The conditioned medium of ESC stimulated with IL-1β and/or BK was injected intraplantarly in mice, and evaluated whether pain-related licking behaviour was elicited.Results: The expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showed that IL-1β induced BKR-B1 and B2 on ESC. Activation of these receptors by BK significantly induced endothelin-1 expression in ESC, which was negated completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma contained higher amount of endothelin-1 compared to non-endometrioma. Intraplantar injection of the conditioned medium of ESC treated with IL-1β and BK significantly induced licking behaviour, which was suppressed with BQ-123, an endothelin type-A receptor antagonist.Conclusions: The present study demonstrated the presence and the function of the BK axis in endometriosis, and established a potential new therapy target for endometriosis-related pain.Significance: The present study demonstrated (1) the presence and the function of the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in endometriotic lesion and (3) blocking endothelin-1 was effective to decrease pain. [ABSTRACT FROM AUTHOR]

The timing of fracture fixation in polytrauma patients has been debated for a long time. The decision between DCO (damage control orthopaedics) and ETC (early total care) is a difficult dilemma. Overzealous ETC in haemodynamically compromised patients with significant chest and head injuries can be detrimental. It has been shown, however, that early fracture fixation has a trend towards better outcome in patients with less severe injuries. Delaying all orthopaedic surgery in critically injured patients can be a safe alternative, but has several disadvantages like longer ICU stay and septic complications. The literature shows equivocal evidence for both settings. This article will summarize the historical background and controversies regarding patient assessment and decision making during the treatment of polytrauma patients. It will also give guidance for choosing DCO versus ETC in the clinical setting. [ABSTRACT FROM AUTHOR]

Uncontrolled bleeding remains a leading cause of potentially preventable death after trauma. Timely, adequate resuscitation in traumatic shock is an essential, lifesaving aspect of polytrauma care. Whilst basic principles in the treatment of traumatic shock remain the same-achieving hemorrhage control and replacing lost volume, the way this is achieved has changed significantly in the last five years. The abandonment of blood pressure driven uncontrolled fluid resuscitation, the introduction of the concept of hemostatic resuscitation, and the increasing use of massive transfusion protocols have all contributed to an improvement in timely access to various blood products. The increase in knowledge regarding the pathophysiology of trauma, the availability of adjuncts, and the array of resuscitation monitoring options available have all contributed to a potentially improved approach to resuscitation. The purpose of this report is to review the most important advances in traumatic shock therapy in the last five years. [ABSTRACT FROM AUTHOR]

B Presenter: b Osamu Yoshino MD | Austin Health and University of Melbourne B Background: b Bile duct injury (BDI) after cholecystectomy remains a substantial problem in gallbladder surgery. Although most cases can be successfully managed by hepaticojejunostomy, few cases with complex BDI would require hepatectomy (HT) and/or liver transplantation (LT). There were 2157 BDI and 163 hepatectomies (7.5 %) and 68 liver transplants (3.1%) were identified among those patients. [Extracted from the article]

Abstract Background Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary. Methods The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining. Results SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol. Conclusions These results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency.

Objective: To investigate the possible impact of thrombin on soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in trophoblasts. Design: Experimental. Setting: University hospital laboratory. Interventions(s): A trophoblast cell line (HRT-8/SVneo) was treated with thrombin, protease-activated receptor 1 (PAR-1)-specific agonist SFLLERN, and thrombin antagonist PPACK. Main Outcome Measure(s): mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in trophoblasts, with the use of real-time polymerase chain reaction; and the secretion of sFlt-1, VEGF, and PlGF protein from trophoblasts, with the use of ELISA. Result(s): Administration of thrombin (10 U/mL) and PAR-1-specific agonist SFLLRN (300 μmol/L) increased sFlt-1 mRNA expression (4.24 ± 0.74- and 4.21 ± 0.79-fold, respectively) and protein secretion (5.08 ± 0.42- and 1.89 ± 0.16-fold, respectively) in HRT-8/SVneo. The induction of sFlt-1 protein secretion by thrombin was dose dependent. The effect of thrombin was completely reduced by thrombin inhibitor PPACK. Thrombin increased mRNA expression of VEGF but did not change VEGF secretion and PlGF mRNA expression and secretion. Conclusion(s): During placental development, thrombin, generated in the local hemorrhage of the uteroplacenta increases trophoblast expression of sFlt-1. Consequently, thrombin may contribute to the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]