Dysregulation of hydrogen sulfide producing enzyme cystathionine γ-lyase contributes to maternal hypertension and placental abnormalities in preeclampsia

Background—The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H2S), a gaseous messenger produced mainly by cystathionine ?-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. Methods and Results—Plasma levels of H2S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8–12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H2S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H2S production. Conclusions—These results imply that endogenous H2S is required for healthy placental vasculature and that a decrease in CSE/H2S activity may contribute to the pathogenesis of preeclampsia. (Circulation. 2013;127:2514-2522.)

Dysregulation of hydrogen sulfide producing enzyme cystathionine γ-lyase contributes to maternal hypertension and placental abnormalities in preeclampsia

Background-The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H2S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. Methods and Results-Plasma levels of H2S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8-12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H2S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H2S production. Conclusions-These results imply that endogenous H2S is required for healthy placental vasculature and that a decrease in CSE/H2S activity may contribute to the pathogenesis of preeclampsia. © 2013 American Heart Association, Inc.

Real-time high-resolution heterodyne-based measurements of spectral dynamics in fibre lasers

Conventional tools for measurement of laser spectra (e.g. optical spectrum analysers) capture data averaged over a considerable time period. However, the generation spectrum of many laser types may involve spectral dynamics whose relatively fast time scale is determined by their cavity round trip period, calling for instrumentation featuring both high temporal and spectral resolution. Such real-time spectral characterisation becomes particularly challenging if the laser pulses are long, or they have continuous or quasi-continuous wave radiation components. Here we combine optical heterodyning with a technique of spatiooral intensity measurements that allows the characterisation of such complex sources. Fast, round-trip-resolved spectral dynamics of cavity-based systems in real-time are obtained, with temporal resolution of one cavity round trip and frequency resolution defined by its inverse (85 ns and 24 MHz respectively are demonstrated). We also show how under certain conditions for quasi-continuous wave sources, the spectral resolution could be further increased by a factor of 100 by direct extraction of phase information from the heterodyned dynamics or by using double time scales within the spectrogram approach.

Cadmium in the environment and high risk population groups

Cadmium has been widely used in various industries for the past fifty years, with current world production standing at around 16,755 tonnes per year. Very little cadmium is ever recycled and the ultimate fate of all cadmium is the environment. In view of reports that cadmium in the environment is increasing, this thesis aims to identify population groups 'at risk' of receiving dietary intakes of cadmium up to or above the current Food and Agricultural Organisation/World Health Organisation maximum tolerable intake of 70 ug/day. The study involves the investigation of one hundred households (260 individuals) who grow a large proportion of their vegetable diet in garden soils in the Borough of Walsall, part of an urban/industrial area in the United Kingdom. Measurements were made of the cadmium levels in atmospheric deposition, soil, house dust, diet and urine from the participants. Atmospheric deposition of cadmium was found to be comparable with other urban/industrial areas in the European Community, with deposition rates as high as 209 g ha-1 yr-1. The garden soils of the study households were found to contain up to 33 mg kg-1 total cadmium, eleven times the highest level usually found in agricultural soils. Dietary intakes of cadmium by the residents from food were calculated to be as high as 68 ug/day. It is suggested that with intakes from other sources, such as air, adventitious ingestion, smoking and occupational exposure, total intakes of cadmium may reach or exceed the FAO/WHO limit. Urinary excretion of cadmium amongst a non-smoking, non-occupationally exposed sub-group of the study population was found to be significantly higher than that of a similar urban population who did not rely on home-produced vegetables. The results from this research indicate that present levels of cadmium in urban/industrial areas can increase dietary intakes and body burdens of cadmium. As cadmium serves no useful biological function and has been found to be highly toxic, it is recommended that policy measures to reduce human exposure on the European scale be considered.

High-performance human resource practices, citizenship behaviour and organizational performance:A relational perspective

Taking a relational perspective on the employment relationship, we examined processes (mediation and moderation) linking high-performance human resource practices and productivity and turnover, two indicators of organizational performance. Multilevel analysis of data from hotels in the People's Republic of China revealed that service-oriented organizational citizenship behavior (OCB) partially mediated the relationships between high-performance human resource practices and both performance indicators. Unemployment rate moderated the service-oriented OCB-turnover relationship, and business strategy (service quality) moderated the service-oriented OCB-productivity relationship. Copyright of the Academy of Management, all rights reserved.

Cholecystokinin (CCK) and CCK receptor expression by human gliomas:evidence for an autocrine/paracrine stimulatory loop

Cholecystokinin (CCK) is a gut-brain peptide has been described to be able to induce mitosis according to recent studies. Additionally, conflicting data has been published on whether tumours of the central and peripheral nervous system in general, and gliomas in particular, express CCK receptors. In the present in vitro study we employed reverse transcription followed by the polymerase chain reaction (RT-PCR) to investigate whether mRNA for CCK-A and CCK-B receptors as well as CCK peptide itself is present in primary human gliomas and the U-87 MG GBM cell line. The data show that 14/14 (100%) of the primary gliomas exhibited mRNA expression for the CCK peptide gene and the B receptor including the U-87 MG cells, whereas, only 2/14 (14%) showed presence of the CCK-A receptor. The presence of CCK receptors together with CCK peptide expression itself suggests presence of an autocrine loop controlling glioma cell growth. In support of this conclusion, a neutralizing antibody against the CCK peptide exhibited a dose dependent inhibition of cell growth whereas, antagonists to CCK caused a dose depend inhibition of exogenous stimulated glioma cell growth in vitro, via the CCK-B receptor which is PKC activated. Assessment of apoptosis and proteasome activity were undertaken and we report that treatment with CCK antagonists decreased proteasome and increased caspase-3 activity. These data indicate that CCK peptide and CCK-B are abundant in human gliomas and they act to stimulate cell growth in an autocrine manner, primarily via the high affinity CCK-B receptor, which was blocked by antagonists to CCK, perhaps via apoptosis.