Nuclear localisation of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) in invasive trophoblasts and an association with recurrent miscarriage

Endocannabinoids are lipid signalling molecules that are related to the major psychoactive component in marijuana, delta-9-tetrahydrocannabinol and are increasingly recognized as being important in implantation and development of early embryos. The endocannabinoid anandamide, is metabolized by the enzyme fatty acid amide hydrolase (FAAH), and insufficient levels of this enzyme have been implicated in spontaneous miscarriage in women and implantation failure in mice. We screened placental bed biopsies and placental tissue from 45 women with recurrent miscarriage and 17 gestation-matched women with normal pregnancies for the expression of FAAH by immunohistochemistry. Unexpectedly, the enzyme appeared to be localised to the nucleus of trophoblasts and this was confirmed by western blotting of sub-cellular fractions and confocal microscopy. FAAH was expressed in the cytoplasm of large decidual stromal cells and significantly more women with recurrent miscarriage (73%) expressed FAAH in these cells than women with normal pregnancy (31%). FAAH was also expressed in the nucleus of extravillous trophoblasts that had invaded the decidua from 67% of women with recurrent miscarriage but was not expressed by these cells in any women with normal pregnancies. In contrast, FAAH was expressed in extravillous trophoblasts that had migrated out of the villi but that had not yet invaded the decidua in both normal pregnancies and in cases of recurrent miscarriage. FAAH was also present in the nucleus of a small number of villous trophoblasts in some specimens. FAAH appears to be over expressed in trophoblasts that have invaded the decidua, as well as in large decidual stromal cells in many cases of recurrent miscarriage. This may reflect inadequate control of the cannabinoid system in the uterus of women who experience recurrent miscarriages. The functional significance of the unexpected nuclear localisation of FAAH in trophoblasts is not yet clear.     

Thrombophilic mutations in pre-eclampsia and pregnancy-induced hypertension

AIM: The aim of the present study was to determine the existence or prevalence of thrombophilic markers such as Factor V Leiden, prothrombin G20210A, protein S, protein C, activated protein C and anti-thrombin in pre-eclampsia and pregnancy-induced hypertensive patients. METHODS: Blood samples were collected from a total number of 124 women at the maternity unit, University of Malaya Medical Center. These included 49 patients with pre-eclampsia, 63 patients with pregnancy-induced hypertension and 12 normal pregnant women. DNA was extracted from the blood samples. Factor V Leiden (Taq I) and prothrombin G20210A (Hind III) genotyping was done on polymerase chain reaction-restriction fragment length polymorphism. Anti-thrombin activity and the concentrations of protein C, protein S and activated protein C were measured using the IL Coagulation System (Hemosil). RESULTS: Of the 124 subjects, one pre-eclampsia patient was homozygous for Factor V Leiden mutation but prothrombin G20210A mutation was not present in any of the subjects. The subject with Factor V Leiden mutation also had a low activated protein C resistance and a low protein S concentration. CONCLUSIONS: Factor V Leiden mutation is present in the Asian population and may very well serve as one of the genetic factors responsible for pre-eclampsia and other adverse pregnancy outcomes.     

Migration and Maternity: Insights of Context,Health Policy,and Research Evidence on Experiences and Outcomes From a Three Country Preliminary Study Across Germany,Canada, and the United Kingdom

A group from Germany, Canada, and the United Kingdom undertook country-specific scoping reviews and stakeholder consultations before joining to holistically compare migration and maternity in all three countries. We examined four interlinking dimensions to understand how international migrant/minority maternal health might be improved upon using transnational research: (a) wider sociopolitical context, (b) health policy arena, (c) constellation, outcomes, and experiences of maternity services, and (d) existing research contexts. There was clear evidence that the constellation and delivery of services may undermine good experiences and outcomes. Interventions to improve access and quality of care remain small scale, short term, and lacking in rigorous evaluation.     

Clipless and sutureless laparoscopic surgery for adrenal and extra-adrenal tumors

BACKGROUND: Newer, energy-based devices like the ultrasonic coagulator (Harmonic Scalpel, Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the LigaSure vessel-sealing system (Valleylab, Boulder, CO) are increasingly being used in advanced laparoscopic procedures. Use of these devices has resulted in shorter operative time, less blood loss, and lower conversion rates. We present our experience with these devices for laparoscopic removal of adrenal and extra-adrenal tumors. METHODS: Ten patients with adrenal tumors and 4 with extra-adrenal tumors were operated on laparoscopically with the ultrasonic shears and LigaSure vessel-sealing system. The entire surgery was carried out using these energy-based devices without using any clips or sutures. RESULTS: No conversions were necessary. None of the patients experienced any major intraoperative or postoperative bleeding. The mean size of the tumor was 6.2 cm (range, 3 to 8). The mean operative time was 123 minutes (range, 80 to 210), and the mean blood loss was 70 mL (range, 10 to 150). Histopathology revealed pheochromocytomas in 7 patients. CONCLUSIONS: Use of the LigaSure vessel-sealing device along with ultrasonic shears for laparoscopic removal of adrenal and extra-adrenal tumors is safe and effective.     

Mechanisms of ENaC regulation and clinical implications

The epithelial Na+ channel (ENaC) transports Na+ across tight epithelia, including the distal nephron. Different paradigms of ENaC regulation include extrinsic and intrinsic factors that affect the expression, single-channel properties, and intracellular trafficking of the channel. In particular, recent discoveries highlight new findings regarding proteolytic processing, ubiquitination, and recycling of the channel. Understanding the regulation of this channel is critical to the understanding of various clinical phenomena, including normal physiology and several diseases of kidney and lung epithelia, such as blood pressure (BP) control, edema, and airway fluid clearance. Significant progress has been achieved in this active field of research. Although ENaC is classically thought to be a mediator of BP and volume status through Na+ reabsorption in the distal nephron, several studies in animal models highlight important roles for ENaC in lung pathophysiology, including in cystic fibrosis. The purpose of this review is to highlight the various modes and mechanisms of ENaC regulation, with a focus on more recent studies and their clinical implications.