[Exercise scenario of a highly contagious, life-threatening disease in intercontinental aviation : a case report in the context of the International Health Regulations (IHR)]. / Übungsszenario für eine hochkontagiöse, lebensbedrohliche Erkrankung in der interkontinentalen Personenluftfahrt : Eine Kasuistik vor dem Hintergrund der internationalen Gesundheitsvorschriften (IGV).

BACKGROUND: The International Health Regulations (IHR) 2005 were conformed to German law on July 20, 2007 and described in detail by the Implementing Act (IHR DG). According to these legal bases, "designated airports" must maintain special capacities for protection against health threats, and are also responsible for performing regular IHR exercises. OBJECTIVES: Representation of the optimization of established operational concepts of various professions to manage infectious biological threats without obstruction of international travel, and mediation of experience to IHR professionals. MATERIALS AND METHODS: An exercise based on the case scenario of a travel-related febrile illness was performed at Munich International Airport on November 11, 2013. Preparations took 6 months and the exercise itself lasted nearly 12 h. The follow-up lasted an additional 9 months. A qualitative and quantitative evaluation of the exercise was completed. RESULTS: From an Individual Medicine and Public Health perspective, modular work structures and risk communication functioned adequately. The medical examination of passengers was also well managed. Areas requiring further optimization included arrival/departure times of external actors, transport of the index patient to hospital and protective measures for individual participants. Overall, a defined biological threat scenario representing a double infection with two highly pathogenic germs was handled satisfactorily without affecting international air travel. CONCLUSIONS: Modular supply components are an effective and forward-looking means in protection against threats occurring at airports. Key success factors include sufficient staff mobility, immediate self-protection of actors involved, effective risk communication and a strong overall coordination and monitoring of the situation.

[Umbilical Absent and Reverse End-Diastolic Flow Velocity Waveforms Already Present Prior to Viability do not Exclude Long-Term Foetal Surveillance: A Report of Two Cases]. / Langzeitüberwachung nach dopplersonografischem Nachweis eines umbilikalen Null- und Rückflusses vor extrauteriner Lebensfähigkeit - 2 Kasuistiken.

The finding of absent or reverse end-diastolic flow velocities (AREDV) in the umbilical artery already prior to viability corresponds to the most severe end of the clinical spectrum of placental insufficiency. However, there is little or no experience or published literature with regard to perinatal outcome. We report 2 cases in which structurally and chromosomally normal foetuses showed severe early onset retardation but were continuing to grow. These gestations could be prolonged by 62 and 64 days, respectively. Perinatal outcome was good in both following Caesarean section at 32+3 and 31+5 gestational weeks respectively.

[Prognostic factors of perinatal short-term outcome in severe placental insufficiency using Doppler sonography to assess end-diastolic absent and reverse blood flow in umbilical arteries]. / Prognosefaktoren des perinatalen Kurzzeitergebnisses bei schwerer Plazentainsuffizienz mit dopplersonografisch enddiastolischem Null- und Rückfluss in der Art. umbilicalis.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

[Spinal anesthesia in high-volume, low-concentration technique for Caesarean sections : Retrospective analysis]. / Spinalanästhesie zur Sectio caesarea in "High-volume-low-concentration"-Technik : Retrospektive Analyse.

BACKGROUND: Nowadays Caesarean sections are mainly undertaken using spinal anesthesia; therefore, it is important to minimize potential side effects and risks associated with this technique. Currently, many studies have been conducted to optimize the dose of local anesthetics to avoid hypotension, which often occurs during spinal anesthesia. AIM: In a retrospective study design the high-volume, low-concentration technique with up to 12 ml isobaric bupivacain 0.1% (1 mg/ml) and sufentanil (1 µg/ml), which has been used at the University Hospital Würzburg for many years was analyzed with respect to reliability and side effects. The use of this technique so far is unique among university hospitals in Germany. MATERIAL AND METHODS: Of the 1424 anesthesia protocols from 2001 to 2007 a total of 1368 were analyzed. Demographic data and parameters, such as location of puncture, dose and extent of anesthesia, hemodynamic stability and additional medication were recorded. A decrease of systolic blood pressure of more than 20% of the initial value was defined as hypotension. RESULTS: The median volume used for spinal anesthesia was 9 ml, containing 9 mg bupivacaine and 9 µg sufentanil. The rate of hypotension was 48.8 %. No significant differences in hypotension between lower and higher volumes were detectable. In 0.84% (n=12) of the cases the procedure had to be changed to general anesthesia and additional analgesia was administered in 3 cases (0.22%). CONCLUSION: The high-volume, low-concentration technique is an effective approach for spinal anesthesia with a small number of cases needing general anesthesia or additional analgesics. The rate of hypotension was moderate compared to other studies; however, because of the retrospective and non-randomized study design the dependence of this rate on dose and given volume should be interpreted with caution.

[Ductus venosus blood flow prior to intrauterine foetal death in severe placental insufficiency can be unaffected as shown by doppler sonography]. / Die Ductus venosus Dopplerflusskurve vor intrauterinem Fruchttod bei schwerer Plazentainsuffizienz mit dopplersono-grafisch enddiastolischem Null- und Rückfluss in der Art. Umbilicalis.

Significant placental insufficiency with Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV) is associated with increased morbidity and mortality. An analysis of blood flow in the ductus venosus assists in the early recognition of threatened foetuses. However, the prognostic value of multivessel Doppler assessment for the timing of delivery is being questioned. Four high-risk pregnancies with umbilical AREDV were repeatedly examined prior to intrauterine foetal demise. Our results demonstrate that ductus venosus Doppler flow velocimetry can be normal prior to intrauterine foetal death.

Targeting of preexisting and induced breast cancer stem cells with trastuzumab and trastuzumab emtansine (T-DM1).

The antibody trastuzumab (Herceptin) has substantially improved overall survival for patients with aggressive HER2-positive breast cancer. However, about 70% of all treated patients will experience relapse or disease progression. This may be related to an insufficient targeting of the CD44(high)CD24(low) breast cancer stem cell subset, which is not only highly resistant to chemotherapy and radiotherapy but also a poor target for trastuzumab due to low HER2 surface expression. Hence, we explored whether the new antibody-drug conjugate T-DM1, which consists of the potent chemotherapeutic DM1 coupled to trastuzumab, could improve the targeting of these tumor-initiating or metastasis-initiating cells. To this aim, primary HER2-overexpressing tumor cells as well as HER2-positive and HER2-negative breast cancer cell lines were treated with T-DM1, and effects on survival, colony formation, gene and protein expression as well as antibody internalization were assessed. This revealed that CD44(high)CD24(low)HER2(low) stem cell-like breast cancer cells show high endocytic activity and are thus particularly sensitive towards the antibody-drug conjugate T-DM1. Consequently, preexisting CD44(high)CD24(low) cancer stem cells were depleted by concentrations of T-DM1 that did not affect the bulk of the tumor cells. Likewise, colony formation was efficiently suppressed. Moreover, when tumor cells were cocultured with natural killer cells, antibody-dependent cell-mediated cytotoxicity was enhanced, and EMT-mediated induction of stem cell-like properties was prevented in differentiated tumor cells. Thus our study reveals an unanticipated targeting of stem cell-like breast cancer cells by T-DM1 that may contribute to the clinical efficacy of this recently approved antibody-drug conjugate.

Studies on the role of osteopontin-1 in endometrial cancer cell lines.

BACKGROUND: Osteopontin-1 is a well characterized protein in many tumour entities. Multiple roles in the processes invasion, metastasis and angiogenesis of tumours are attributed to osteopontin-1. The putative role of osteopontin-1 has not been characterized for endometrial cancer. MATERIAL AND METHODS: We investigated multiple endometrial cancer cell lines for osteopontin-1 mRNA- and protein-expression. Osteopontin-1 dependent effects were analysed in vitro by siRNA inhibition. RESULTS: All endometrial cell lines expressed osteopontin-1. Expression of osteopontin-1 was successfully inhibited by specific siRNA. Cells with reduced osteopontin-1 expression showed decreased migration in the Boyden chamber assay and invasion was reduced in the wound-healing assay. Osteopontin-1 seems to play a role in apoptotic processes of endometrial cancer cells. Inhibition of osteopontin-1 expression was associated with an increased susceptibility for radiation therapy. CONCLUSION: Osteopontin-1 seems to play a role in endometrial cancer. Inhibition of osteopontin-1 expression leads to a higher susceptibility for radiation therapy. Our results suggest that a reduced expression of osteopontin-1 in endometrial cancer could inhibit the development of invasion and metastasis in these cells.

Thrombopoietin modulates the proliferation, migration and cytokine profile of decidual cell subsets during early gestation.

During early gestation, a considerable increase in different leukocyte subsets can be observed in the decidualized endometrium concomitantly to the invasion of cytotrophoblast cells (CTB). To date, it is still in question which factors induce this accumulation of immune cells and whether it is evoked by an in situ proliferation or by a migratory process. Studies on hepatoblastoma cells identified thrombopoietin (TPO) as a novel factor, which elicits dose-dependent chemotactic and chemokinetic effects. However, the impact and function of TPO on decidual cells has not been clarified yet. This study analyses the expression and function of TPO and its receptor c-Mpl in decidua during early gestation. Applying western blot analysis, we detected that TPO is expressed by decidual immune cells (uNK cells and CD14+ monocytes) as well as CTB and decidual stromal cells (DSCs). Expression of the different isoforms of c-Mpl was found in uNK cells, CD14+ monocytes and DSC. Studying the signalling pathway proteins in the uNK cells, an activation of STAT3/Tyr by TPO, was detected. The investigation of the proliferative effects of TPO on the decidual cell subsets revealed that TPO enhances the proliferation of uNK cells and CTB. No change of the proliferative activity after TPO incubation was found in DSC and even a decrease in CD14+ monocytes. In addition, TPO was observed to induce significantly the migratory activity of uNK cells, CD14+ monocytes and CTB. Investigating the effects of TPO on the cytokine profile of the isolated decidual cells, we observed a decrease in the secretion of IL-8, IL-10 and IL-1ß of isolated uNK cells, CD14+ monocytes and CTB, although these changes did not reach statistical significance. Thus, we here identified TPO as a novel factor modulating the proliferation, migration and possibly cytokine secretion of decidual cell subsets.

XY gonadal dysgenesis--development of a germ cell tumor: case report.

Gonadal dysgenesis (GD) is a rare congenital malformation that affects about one in 3,000 births. The authors present a case of a 17-year-old woman with primary amenorrhea and poor breast development. They conducted a laparoscopic surgery and bilaterally removed hypoplastic streak gonads. Histopathology of the ovaries revealed bilateral streak gonads with gonadoblastomas and a right-sided dysgerminoma.

[Severe maternal hepatopathies in the peripartum period--a case series with review of the literature focusing on pathogenesis and differential diagnosis]. / Lebensbedrohliche, maternale Leberaffektionen in der späten Schwangerschaft und im Wochenbett--eine Fallserie mit Überblick über Pathogenese und differenzialdiagnostische Abgrenzung.

BACKGROUND: A severe hepatopathy constitutes a serious threat during pregnancy and poses considerable challenges to the treating physicians. A broad spectrum of pregnancy-dependent or independent diseases like HELLP-syndrome, liver infection or acute fatty liver of pregnancy (AFLP) is characterized by these affections of the liver. In this study, we present a series of 3 cases with life-threatening hepatopathies and discuss the current state of the literature. A special focus is placed on pathogenesis and differential diagnosis. METHODOLOGY: Pathological, radiological and gynaecological/surgical procedures were performed according to the current German guidelines. Laboratory tests were conducted in the clinics' routine diagnostics section. The existing literature was reviewed via the US National Library of Medicine database "PubMed.gov". RESULTS: The first patient had been afflicted by a fulminant HELLP syndrome causing delivery after 32 weeks of pregnancy. Consecutively, she suffered a sub-total liver infarction followed by a severe coagulopathy and septic peritonitis. The second patient was diagnosed with HELLP syndrome at 36 weeks of pregnancy. The initially mild syndrome exacerbated after delivery leading to haemorrhagic shock and acute renal failure. In the third case, a woman with asymptomatic hepatitis B delivered in the 36th week of pregnancy. Post partum, her pre-existing condition worsened fulminantly resulting in sub-acute liver dystrophy and massive coagulopathy. DISCUSSION AND CONCLUSION: Whenever a hepatopathy occurs during pregnancy, several divergent diagnoses with severe implications and different aetiopathologies have to be considered. Diagnostic and therapeutic strategies have to be weighed quickly to enable a fast, interdisciplinary cooperation in order to prevent fatal outcomes.

Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro.

Platinum resistance is the most crucial problem for treatment of ovarian cancer. Increasing evidence points towards AKT overexpression as a mechanistic reason for this clinical condition. The present study evaluates the effect of overexpression and downregulation of AKT on the sensitivity to cisplatin in a platinum-resistant human ovarian cancer cell line and the corresponding platinum-sensitive parental cell line. A2780 and A2780cis ovarian cancer cell lines were stably transfected with an AKT-sense and AKT-antisense plasmid. Successful transfection was evaluated by western blot analysis. Cytotoxic effects of cisplatin were evaluated by metabolic (MTT) and clonogenicity assays as well as by FACS analysis. AKT overexpression (confirmed by western blotting) converted platinum-sensitive A2780 into platinum-resistant cells as shown by MTT assay. Importantly, platinum resistance of A2780cis cells could be reversed by downregulation of AKT, as demonstrated by MTT and clonogenicity assays and FACS analysis. Our data provide strong evidence that cisplatin resistance in ovarian cancer is mediated by AKT overexpression and can be overcome by AKT downregulation, thus, providing a rationale for clinical phase II/III studies combining AKT inhibitors with cisplatin.

[Acute foeto-foetal transfusion syndrome--case report and review of the literature]. / Akutes fetofetales Transfusionssyndrom--Fallbericht und Literaturübersicht.

The perinatal morbidity and mortality risk in monochorionic twin pregnancies are 3-5-fold increased compared to those of dichorionic twin pregnancies. Partially, this is due to the higher rate of preterm delivery but also to the twin-to-twin transfusion syndrome (TTTS). Caused by unidirectional blood flow via placental anastomoses, the TTTS leads to weight differences of more than 20% between monochorial twins. The blood donor often shows oligohydramnios, whereas the recipient shows polyhydramnios. Lewi et al. demonstrated, in a study with 202 monochorionic twin pregnancies, a 9% rate of severe TTTS. The mortality of this complication is about 90% when untreated. In contrast to the chronic TTTS, little is known about the acute intrapartal one, which is characterised by anaemia and hypovolaemia of the donor and polyglobulia of the recipient without significant weight differences between the two. In most cases, anaemia occurred after normal delivery of the first twin. Still, there are no means or signs for early detection. We describe the case of a 30-year-old primigravida with a monochorionic diamniotic twin pregnancy. During pregnancy, no evidence of TTTS could be detected. At 37 + 1 weeks gestation labour was induced with prostaglandin-containing gel. Both foetuses showed cephalic presentation. The CTG of the first twin showed a conspicuous heart rate. After labour the first twin presented with anaemia and hypovolaemic shock, the APGAR was 2/7/8. The infant's haemoglobin was 13.7 g/dL. After delivery, the second twin with APGAR 10/10/10 showed a haemoglobin of 19.6 g/dL, which is in the upper normal range. Their birth weights differed by merely 10.4%. Acute TTTS is frequently characterised by anaemia and hypovolaemia of the second twin. In our case of a monochorionic twin delivery with acute TTTS the donor was born first. Early diagnosis and neonatal intervention is essential for reducing postnatal morbidity and mortality.

PI3K inhibitor D-116883 is effective in in vitro models of ovarian cancer.

BACKGROUND: D-116883 (Aeterna Zentaris GmbH, Frankfurt, Germany) is an orally effective drug that acts via inhibition of phosphatidylinositol 3-kinase (PI3K). The PI3K/AKT signal transduction pathway is involved in ovarian cancer tumorigenesis. Phosphatase and Tensin homolog (PTEN) loss and other activating mutations frequently contribute to the activation of this pathway. We tested whether D-116883 exerts cytostatic effects in in vitro models of ovarian cancer and analyzed the induced programmed cell death. MATERIALS AND METHODS: We evaluated the potency of D-116883 in four ovarian carcinoma cell lines with different cellular assays. The effects of D-116883 on cell proliferation was analysed by crystal-violet staining and tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay. The capacity for anchorage-independent growth was analyzed in two ovarian carcinoma cell lines without and with D-116883 addition by using the soft agar assay. Fluorescence activated cell sorting (FACS) cell cycle analyses were performed. Cells were incubated with multicaspase inhibitor benzyloxycarbonyl-val-ala-asp(OMe)-fluoromethylketone (zVAD) and inhibitor of necroptosis necrostatin. RESULTS: Growth inhibition occurred in all ovarian carcinoma cell lines studied (A2780, A2780cis, OAW42 and SKOV3) in a micromolar range (IC(50)<1 µM). By using soft agar assay, a reduced capacity for anchorage-independent growth, a hallmark of tumor cells, caused by D-116883 was demonstrated. Cell cycle analyses showed that D-116883 dose-dependently increased apoptotic cells. Multicaspase inhibitor zVAD and inhibitor of necroptosis necrostatin did not abrogate the growth-inhibiting effect of the compound. CONCLUSION: PI3K inhibitor D-116883 showed substantial cytotoxic effects in various in vitro models of ovarian cancer. Our results make D-116883 a good candidate for further ovarian cancer research including in vivo experiments.

Peptidomimetic GnRH antagonist AEZS-115 inhibits the growth of ovarian and endometrial cancer cells.

BACKGROUND: AEZS-115 (Aeterna Zentaris GmbH, Frankfurt/M, Germany) is an orally active peptidomimetic antagonist of gonadotropin-releasing hormone (GnRH). In various tumors, an autocrine growth-promoting loop has been described for GnRH. The current study evaluates the antitumor activity and mechanism of action of AEZS-115 in models of ovarian and endometrial cancer. MATERIALS AND METHODS: Human A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells were analyzed for GnRH receptor expression by reverse transcription polymerase chain reaction (RT-PCR). These cell lines were incubated with AEZS-115 at 1, 10 and 100 µM for 24 h, 48 h, and 72 h and the number of viable cells was determined. Fluorescence activated cell sorting (FACS) cell cycle analyses were performed with increasing concentrations of AEZS-115. Co-treatment experiments of cancer cells with GnRH antagonist cetrorelix and peptidomimetic GnRH antagonist AESZ-115 were carried out. RESULTS: A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells expressed GnRH receptors as demonstrated by RT-PCR. GnRH antagonist AEZS-115 inhibited growth of all cell lines in a dose- and time-dependent manner. Half maximal inhibitory concentration (IC(50)) values at 48 h of incubation were between 7 and 17.5 µM and for 72 h between 4.5 and 12.5 µM. IC(50) values for ovarian and endometrial cancer cells were rather similar. These results were obtained by tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay and confirmed by additional crystal violet staining. Cell cycle FACS analysis revealed that AEZS-115 dose-dependently increased the fraction of apoptotic cells. Co-treatment experiments carried out with AEZS-115 and peptidic GnRH-antagonist cetrorelix suggest that the antitumor effect of AEZS-115 is not mediated by blockade of the GnRH receptor. CONCLUSION: GnRH antagonist AEZS-115 exhibited substantial antitumor activity in ovarian as well as endometrial cancer cell lines. However, this antitumor effect was not mediated by the tumoral GnRH receptors. To identify the mechanism of action of this compound, further research is warranted. Its in vitro antitumor activity makes AEZS-115 a promising candidate for in vivo studies of ovarian and endometrial cancer.

[Sonographic abnormalities of the fetal CNS in the second trimester screening--clarifications according to the new maternity directives]. / Sonografische Auffälligkeiten des fetalen ZNS im Zweittrimesterscreening--Abklärung nach neuen Mutterschaftsrichtlinien.

Malformations of the central nervous system are among the most frequent congenital anomalies. At best, a qualified and standardised screening of the foetal brain is possible between the 18th and the 22nd week. The newly decided modification of the maternity directives envisages an extended screening upon request. This extended screening refers to the central nervous system and the representation of the ventricles, the evaluation of the head shape and the cerebellum and the back. The examination of the foetal brain should be carried out in a structured way. Three axial planes, the transventricular, the transthalamic and the transcerebellar planes, suffice to represent and measure all structures which are of importance for the screening. In case of ventricular anomalies, anomalies of the head shape, anomalies of the cerebellum and irregularities of the dorsal skin outlined in the second screening a further diagnostic procedure should be initiated. This diagnostic work-up should include a detailed neurosonography, a diagnostic evaluation of the organs and eventually further examination in the form of a caryotyping, determination of the infectology or a foetal MRI. The present article offers an overview of possible CNS abnormalities which could be recognised during the second screening according to the extended maternity directives and describes which differential diagnostics should be considered. In detail, anomalies of the head size (microcephaly, macrocephaly), of the head size (brachycephaly, dolichocephaly, cavities of the cranium, banana sign, etc.,), ventricular abnormalities, anomalies of the cerebellum (cerebellum hypoplasia, abnormal cerebellum shape) and abnormalities of the intermediate line and the intracerebral space requirements are discussed.

MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts.

BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1) is a multifunctional cytokine produced in high amounts by placental tissue. Inhibiting trophoblast invasion and suppressing inflammation through inhibition of macrophage activation, MIC-1 is thought to provide pleiotropic functions in the establishment and maintenance of pregnancy. So far, little is known about the decidual cell subsets producing MIC-1 and the effect of this cytokine on dendritic cells (DCs), which are known to play a distinct role in the development of pro-fetal tolerance in pregnancy. METHODS: To identify the decidual cell types expressing and secreting MIC-1, immunohistochemical staining, PCR experiments, western blot analysis and ELISAs were performed. Immature DCs (iDCs) were generated from peripheral blood-derived monocytes and differentiated in the presence of MIC-1 or dexamethasone (Dex) for control. Migratory and proliferative activity of DCs after MIC-1 exposure was investigated by migration and proliferation assay. Cytokine secretion after MIC-1 exposure was tested in isolated uNK cells, isolated CD14+ monocytes, monocyte-derived iDCs and mature DCs. Subsequently, the phenotype of DCs was studied using FACS analysis. To test the T-cell stimulatory capacity of pre-incubated DCs, mixed lymphocyte reaction was applied. Finally, the expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) after the exposure of MIC-1 to maturing DCs was analysed by western blot. RESULTS: Immunohistochemical staining, PCR and western blot experiments demonstrated that MIC-1 is mainly expressed by trophoblast cells and decidual stromal cells. Analysis of the MIC-1 secretion of decidual cell types by ELISA again characterized trophoblast and stromal cells as main producers. The migratory activity of iDCs was significantly induced by MIC-1. No changes in proliferative activity of DCs were observed after MIC-1 pre-incubation. The secretion of pro- or anti-inflammatory cytokines was not affected significantly by MIC-1. Studying the phenotype of DCs after MIC-1 exposure by FACS analysis, we observed that MIC-1 suppresses the expression of typical maturation molecules such as CD25 and CD83 as well as of CD86 during cytokine-induced DC maturation similar to Dex. In addition, T-cell stimulatory capacity of DCs was significantly reduced after MIC-1 exposure. MIC-1 was also able to increase slightly the expression of IDO (a key immunomodulatory enzyme promoting periphereal tolerance) in maturing DCs. CONCLUSIONS: We have identified MIC-1 as a novel factor (secreted by decidual cells in early pregnancy) that could promote the increase of a tolerogenic subtype of DC in decidua.

[Myocardial infarction in the 34th week of gestation: case report]. / Myokardinfarkt in der 34. Schwangerschaftswoche.

Acute myocardial infarction during pregnancy is a rare event that is often associated with a very high maternal mortality, estimated to be from 19 to 37%. During the last decades the incidence of myocardial infarction during pregnancy has increased . The main contributing factor could be a higher prevalence of the metabolic syndrome. The strongest predictors correlated with a myocardial infarction are hypertension, diabetes mellitus and advanced maternal age. In addition, improved diagnostic tools could explain the elevated incidence of myocardial infarction during pregnancy. In general gestation is not considered a risk factor for myocardial infarction but gravidity is accompanied by an increase in oestrogen and progesterone levels. It is generally accepted that oral contraceptives increase the risk of coronary heart disease. We present a case where a 37-year-old gravida was admitted to hospital with diffuse thoracic pain. In the patient's history, we found several putative reasons for the thoracic pain that pointed to a musculoskeletal cause. Based on an elevation of ischaemic heart markers and continuous non-specific thoracic pain we performed a primary Cesarean section. In the coronary angiography procedure that followed, a thrombotic occlusion of the ramus diagonalis was diagnosed. We here describe the differential diagnosis as well as the problems associated with diagnosing myocardial infarction in the third trimester of pregnancy.