Endometrial perfusion across the normal human menstrual cycle assessed by laser Doppler fluxmetry

This study investigated variations in microvascular perfusion of human endometrium across the menstrual cycle, using a laser Doppler technique to assess red blood cell (RBC) flux. Endometrial RBC flux was monitored by laser Doppler fluxmetry via a fibre optic probe inserted transvaginally into the uteri of 19 conscious normal volunteer women, on four occasions at weekly intervals over one menstrual cycle. Regional variation in RBC flux was investigated in 16 surgical patients under general anaesthesia and in five excised uteri. Endometrial perfusion exhibited short-term temporal variations consistent with the cardiac cycle and often also showed vasomotion (5-12 cycles/min). Mean endometrial perfusion differed between phases of the menstrual cycle in conscious women, being highest during early proliferative and early follicular phases. There were no significant regional differences in local mean endometrial perfusion in anaesthetized patients. No evidence of endometrial ischaemia/reperfusion episodes was found in any subject using this technique. This study provides benchmark data of variations in RBC flux per unit volume of tissue in the luminal approximately 1 mm of endometrium, across the normal human menstrual cycle. Flux values were highest at times associated with endometrial growth and preparation for implantation, indicating that RBC flux may be a useful parameter for assessment of endometrial physiology.      

The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits

We have compared the hemorrhagic and antithrombotic effects of a low molecular weight (LMW) heparin fraction and standard heparin in rabbits. Similar LMW heparin fractions have antithrombotic effects when tested in animals, but their hemorrhagic effects relative to standard heparin have not been established. Standard porcine mucosal heparin (mol wt 15,000 daltons) was depolymerized by nitrous acid to a low molecular weight fraction (mol wt 4600 daltons). Using equal USP units, the standard and Dep LMW heparin were compared in vitro, ex vivo, and in vivo. In vitro, when diluted in rabbit plasma, the Dep LMW heparin at equivalent anti-Xa activity showed less prolongation of thrombin clotting times or activated partial thromboplastin times. Ex vivo, platelets from rabbits treated with the Dep LMW heparin showed less inhibition of collagen-induced aggregation. The relative hemorrhagic properties of the two heparins were compared in vivo in rabbits using a sensitive blood loss assay, and the antithrombotic properties were compared in a thrombin-induced venous stasis model. By using an optimal threshold heparin dose in each test system, it was possible to demonstrate that equal USP units of Dep LMW heparin caused less blood loss but showed greater antithrombotic activity than standard heparin.     

Schwangerschaft und maternales Immunsystem

Pregnancy is a successful natural model of immune tolerance. The fetus is not only passively tolerated by the maternal immune system – it is actively supported in its development (immunotrophism), which is in apparent conflict with the primary mechanism of transplantation immunology (recognition of foreign bodies). Its ‘invasive’ growth is made possible by an immunologic situation whose characteristics are being more and more understood. However, disbalance in this fine network can lead to disturbances in implantation and placentation and result in intrauterine growth retardation or spontaneous miscarriage. Understanding immunologic communication at the trophoblastic level can improve understanding of other invasive processes, for example those of malignant degeneration, and open new therapeutic possibilities. We describe three main functions of the immune system that apply in the fetomaternal interphase: (1) trophoblast immune function and the cytokine network, (2) uterine natural killer cells, and (3) the function of the immunosuppressive glycoprotein glycodelin. Current recommendations for immunotherapy in case of recurrent miscarriage are discussed.     

群勃龙及其人尿代谢物的GC/MSD分析

群勃龙(去甲雄三烯醇酮,trenbolone)在MsTFA,MBTFA,MO-MSTFA衍生化后形成的TMS醚式和TFA酯化产物,经GC/MSD分析,获得各自的特征图谱,讨论了有关的衍生化问题。群勃龙阳性尿样分析结果显示,其主要代谢产物是表群勃龙(epitrenbolone)和可能的羟基群勃龙(hydroxy-trenbolone),另有少量原型以及可能有去甲雄三烯二酮(triendione)存在。     

Fibrillin‐1 staining anomalies are associated with increased staining for TGF‐β and elastic fibre degradation; new clues to the pathogenesis of emphysema

We recently demonstrated aberrant staining of fibrillin‐1 in lung tissue specimens with emphysematous lesions. In this study, we have extended this observation by an elaborate analysis of the elastic fibre. Using domain‐specific antibodies to fibrillin‐1, and to other elastin fibre‐associated molecules, lung tissue derived from patients without obvious clinical emphysema, but harbouring various degrees of microscopical emphysematous lesions, was analysed. In addition, the fibrillin‐regulated growth factor TGF‐β was studied. Electron microscopy and biochemical analysis of desmosine (a marker for elastin) were also performed. Results were compared with lung tissue derived from patients with clinical emphysema. Domain‐specific antibodies recognizing the C‐terminal, N‐terminal, and middle part of fibrillin‐1 showed aberrant staining patterns associated with increasing degrees of microscopical emphysema. Staining for elastin, emilin‐1, and fibulin‐2 was, however, not aberrant. TGF‐β staining was markedly increased. On the electron microscopic, but not light microscopical, level, initial elastic fibre degradation was noticed in specimens with microscopical emphysema. Lung specimens from patients with clinical emphysema also displayed fragmented fibrillin‐1 staining and, in addition, displayed extensive degradation of the elastic fibre. The results suggest that fibrillin‐1 anomalies and TGF‐β overexpression are associated with initial events occurring during the emphysematous process. Based on these and other data, a mechanism for emphysematogenesis is proposed. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Headache syndromes after acoustic neuroma surgery and their implications for quality of life

The patients of this prospective study were analysed for headache as a sequela of surgery for acoustic neuroma (AN). Thirty-two per cent (30/95) of patients complained about a persisting headache syndrome with a severity of at least 6/10 on the nominal analogue scale 6 months after surgery. The occurrence of headache was significantly correlated with the prospectively evaluated parameters preoperative headache and the number of perioperative complications. Postoperative failure to return to the preoperative level of activity was also associated with the occurrence of headache, but also with the risk of retirement after successful surgery of the AN. Headache is therefore, like postoperative ataxia, dysgeusia and probably facial paresis, an important factor for the overall outcome of patients after AN surgery. Hypacusis is not as important. The symptoms and course of each individual patient were analysed. The attempt to categorize the headaches according to the second edition of the International Classification of Headache Disorders revealed five headache syndromes, the most prevalent being tension-type-like headache (46.7%), followed by neuralgia of the occipital nerve (16.6%), trigeminal neuropathy (16.6%), neuropathy of the intermedian nerve (10.0%) and cervicogenic headache (10.0%). The respective pathophysiological mechanisms are discussed and treatment options based on the clinical picture are presented.     

Oxidative inactivation of plasmin and other serine proteases by copper and ascorbate

Fibrin thrombi form at sites of injury, where leukocytes release a variety of oxidants. To determine whether oxidants might affect proteins of the fibrinolytic system, we examined the effects of various oxidants on plasmin. Plasmin was not inhibited by micromolar concentrations of hypochlorous acid, chloramine T, or H2O2. Neither Fe nor Cu affected plasmin alone or in the presence of H2O2. However, incubation of plasmin with 5 mumol/L Cu(I or II) in the presence of the reducing agent ascorbic acid resulted in a loss of its hydrolytic activity towards proteins as well as towards small synthetic substrates. The addition of EDTA, but not mannitol, prevented its inactivation. Inactivation was prevented by the addition of catalase and accelerated by hydrogen peroxide. Preincubation of plasmin with the competitive inhibitor alpha-N-acetyl-L-lysine methyl ester prevented inactivation by Cu(II) and ascorbate. These results together suggest site-specific oxidation of plasmin's active site. Treatment of the plasminogen activators tissue plasminogen activator and two-chain urokinase-type plasminogen activator, as well as trypsin, neutrophil elastase, and thrombin with Cu(II) and ascorbate resulted in a loss of their amidolytic and proteolytic activity, indicating the general susceptibility of serine proteases to this type of oxidation. Oxidation of the zymogens Glu-plasminogen and single-chain urokinase-type plasminogen activator by Cu(II) and ascorbate resulted in the failure of these molecules to generate active enzymes when treated with plasminogen activators or plasmin, respectively. The active site His residue may be the target of oxidative inactivation, as evidenced by the partial protection afforded plasmin by the addition of Zn(II), histidine, or the platinum derivative, platinum(II) (2,2':6',2"- terpyridine) chloride. Because platelets contain micromolar concentrations of Cu and leukocytes are rich in ascorbate, Cu-dependent site-specific oxidation might play a role in modulating proteolytic events and the life span of thrombi formed at sites of tissue injury.