The obstetric antiphospholipid syndrome

The association of persistent presence of circulating antiphospholipid antibodies and thromboembolic events, (recurrent) pregnancy loss or both is termed antiphospholipid syndrome. Pregnancies in women with the syndrome should be regarded as at high-risk for complications. Optimal management consisting of close follow-up and pharmacological treatment can result in about 70-80% live births. Apart from the laboratory diagnosis of the syndrome and pathophysiology, this review will focus on treatment during pregnancy.     

STOX1 gene in pre-eclampsia and intrauterine growth restriction

The STOX1 gene, identified as a candidate gene for pre-eclampsia in Dutch women, is placentally expressed and subject to imprinting with preferential transmission of the maternal allele. In our study, STOX1 -Y153H frequencies were similar in 157 women with pre-eclampsia (65%) and in 157 controls (64%) from the general Dutch population. In an isolated Dutch population, a distortion could not be demonstrated in the transmission of STOX1 -Y153H variation from heterozygous mothers to offspring in 50 and 56 families with pregnancies complicated by pre-eclampsia or intrauterine growth restriction, respectively. Our findings do not confirm previous suggestions that STOX1 plays a major role in Dutch women with pre-eclampsia.     

A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],     

Improvement of the cold storage of blood vessels with a vascular preservation solution. Study in porcine aortic segments

BACKGROUND: Cold-induced injury to various cell types has been shown to be mediated predominantly by chelatable iron. For endothelial cells, this type of injury has so far only been shown in cultured cells. Hypothesizing that this iron-dependent cold-induced injury might also occur in the endothelium of intact vessels, we here set out to optimize the hypothermic storage of blood vessels. METHODS: Segments of porcine aorta were stored for 2 to 21 days in histidine-tryptophan-ketoglutarate (HTK) solution or in modified solutions with or without the iron chelators deferoxamine or LK 614 at 4 degrees C. Parts of the segments were assayed immediately after cold storage, the other parts after subsequent rewarming. The percentage of dead (propidium iodide-positive) endothelial cells was assessed by "intravital" fluorescence microscopy, mitochondrial membrane potential was assessed by laser scanning microscopy after staining with tetramethylrhodamine methyl ester (TMRM) and thrombocyte adhesion was studied using 5-(and -6)-carboxy SNARF-1-stained thrombocytes. RESULTS: The endothelium of porcine aortic segments sustained moderate injury during the cold incubation itself, but major injury during rewarming. The addition of the iron chelator deferoxamine (1 mmol/L) significantly inhibited cold-induced endothelial cell injury irrespective of the solution used for cold storage (eg, 14 days of cold storage + 3 hours rewarming: HTK 66 +/- 7%, HTK + 1 mmol/L deferoxamine 40 +/- 10% propidium iodide-positive endothelial cells). An amino acid (glycine, alanine, aspartate)-containing base solution with N-acetylhistidine as buffer was optimized. The optimized base solution with pH 7.0 and potassium and chloride as main ions yielded a further decrease of endothelial cell injury. Combination of deferoxamine (in lower concentration, ie, 0.1 mmol/L) with the new, more membrane-permeable iron chelator LK 614 (20 mumol/L) further improved preservation so that even after 3 weeks of cold storage plus 3 hours rewarming only 10 +/- 1% of endothelial cells were propidium iodide positive. In this optimized solution, both endothelial cell survival and mitochondrial membrane potential were significantly better preserved than in the clinically used solutions HTK, University of Wisconsin (UW) and Perfadex, or in physiological saline. Thrombocyte adhesion was also significantly reduced after cold storage in the optimized solution compared with HTK solution. CONCLUSION: Cold-induced injury to the endothelium of porcine aortic segments is, as the injury to cultured endothelial cells, mediated by chelatable iron. Thus, iron chelators, but also optimized base solutions, are options to improve the storage of vascular endothelium. The optimized solution should now be tested in in vivo animal experiments.     

Effects of enriched housing on functional recovery after spinal cord contusive injury in the adult rat

To date, most research performed in the area of spinal cord injury focuses on treatments designed to either prevent spreading lesion (secondary injury) or to enhance outgrowth of long descending and ascending fiber tracts around or through the lesion. In the last decade, however, several authors have shown that it is possible to enhance locomotor function after spinal cord injury in both animals and patients using specific training paradigms. As a first step towards combining such training paradigms with pharmacotherapy, we evaluated recovery of function in adult rats sustaining a spinal cord contusion injury (MASCIS device, 12.5 mm at T8), either housed in an enriched environment or in standard cages (n = 15 in both groups). The animals in the enriched environment were stimulated to increase their locomotor activity by placing water and food on opposite sides of the cage. As extra stimuli, a running wheel and several other objects were added to the cage. We show that exposure to the enriched environment improves gross and fine locomotor recovery as measured by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, the BBB subscale, the Gridwalk, and the Thoracolumbar height test. However, no group differences were found on our electrophysiological parameters nor on the amount of spared white matter. These data justify further studies on enriched housing and more controlled exercise training, with their use as potential additive to pharmacological intervention.     

The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) could extend the duration of response of androgen sensitive prostate cancers to androgen deprivation. METHODS: We investigated the effect of new GHRH antagonists MZ-J-7-118 and MZ-J-7-138 and luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix or castration on androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancer models xenografted into nude mice. Animals bearing androgen-independent LuCaP-35V prostatic cancer model were also treated with MZ-J-7-118. RESULTS: Receptors for LHRH and GHRH were present in MDA-PCA-2b, LuCaP-35, and LuCaP-35V tumors. GHRH antagonists increased the inhibitory effect of surgical castration and LHRH antagonists on androgen sensitive MDA-PCa-2b and LuCaP-35 tumors. The time to relapse of androgen-dependent LuCaP-35 tumors was extended by GHRH antagonists. Growth of androgen-independent LuCaP-35V xenografts was also significantly inhibited by MZ-J-7-118. In MDA-PCa-2b tumors treatment with MZ-J-7-118 caused a significant decrease of VEGF and Cetrorelix or its combination with MZ-J-7-118 reduced EGF. The B(max) of EGF receptors was significantly reduced by Cetrorelix, MZ-J-7-118 and their combination. CONCLUSIONS: Our findings suggest that the use of a combination of antagonists of GHRH and LHRH could improve the therapy for androgen sensitive prostate cancer. Antagonists of GHRH could be also considered for treatment of androgen-independent prostate cancers.