P-glycoprotein belongs to the ATP binding cassette transporters, responsible for the multidrug resistance of cancer cells. These transporters efflux hydrophobic drugs outside cells and decrease their therapeutic efficacy. The aim of this study was to investigate the effect of vandetanib, an oral tyrosine kinase inhibitor of EGFR, VEGFR 2 and RET kinases, on the functionality of P-gp after a 24h-treatment at therapeutic concentration (2μM), and its ability to increase the cytotoxicity of chemotherapeutic agents in multidrug resistance cancer cells. In this study we found that IGROV1-DXR and IGROV1-CDDP cells were resistant to doxorubicin and cisplatin respectively, compare to parental cell line IGROV1. The parental sensitive and the two resistant cell lines similarly expressed MRP1 and did not express BCRP. Moreover, in contrast to the IGROV1 and IGROV1-CDDP cells, IGROV1-DXR cell line overexpressed P-gp. Functional activity studies demonstrated that MRP1 was not functional and the MDR phenotype in IGROV1-DXR cells was linked to P-gp functionality. Results also showed that vandetanib reversed resistance to doxorubicin in IGROV1-DXR cells, but not to cisplatin in IGROV1-CDDP cells. After 24h of treatment, vandetanib increased the accumulation of rhodamine 123 and calcein AM, demonstrating a functional inhibition of the transporter. In IGROV1-DXR cell line, vandetanib reverse resistance to doxorubicin by inhibiting the functionality of P-gp. In conclusion, vandetanib should be an option for drug combination in patients already developing a P-gp mediated multidrug resistance.

Perfused human placental lobule was developed during the 1970s Only this model respects the anatomical features of the human placenta This approach allows different technical conditions (concentrations of drugs) without ethical problems Limitations of this ex vivo model are detailed in this review, also its recent contributions in better understanding of placental passage of drugs (C) 2010 Elsevier Masson SAS All rights reserved

The aim of this work is to describe the techniques that have been used for preparation and analysis of whole fetal liver extracts destined for in utero transplantation. Nine fetal livers between 12 and 17 weeks of gestation were prepared: cell counts and assessment of the hematopoietic cell viability were performed on cell suspensions. Hepatocytes represented 40 to 80% of the whole cell population. The remaining cells were constituted by hematopoietic cells (mainly erythroblasts), as well as by endothelial cells. The latter expressed CD34 on their surface, interfering with the assessment of CD34 + hematopoietic cells by flow cytometry. Direct visual morphologic control using alkaline phosphatase anti-alkaline phosphatase techniques was needed to differentiate hematopoietic from extra-hematopoietic CD34 + cells. Between 3.0 and 34.6 × 10 6 CD34 + viable hematopoietic cells were collected per fetal liver. Adequate differentiation of these cells into burst-forming units erythroid (BFU-E), colony-forming units granulocyte–macrophage (CFU-GM), and colony-forming units granulocyte erythroid macrophage megakaryocyte (CFU-GEMM) has been shown for each sample in clonogeneic cultures. In conclusion, fetal liver is a potential source of hematopoietic stem cells. Their numeration, based on the presence of CD34, is hampered by the expression of this antigen on other cells contained in the liver cell extract, in particular endothelial cells. Bone Marrow Transplantation (2000) 26 , 667–671.

Thirteen cases of fetal parvovirus B19 infection with hydrops foetalis are reported. Viral DNA was identified by polymerase chain reaction (PCR) of amniotic fluid sampled between the 19th and the 29th week of gestation. Haematological examination revealed severe anaemia in all cases and thrombocytopenia in 11/13 cases, which was severe in two cases. Six fetuses died in utero; two after intrauterine transfusion. Complete recovery was observed in seven fetuses; five cases were treated by intrauterine transfusions, and in two cases spontaneous recovery occurred. Upon follow‐up, no case of congenital anaemia was observed.

Infection with Varicella Zoster Virus during pregnancy is a rare condition. Chikenpox can lead to various complications:Maternal complications with the risk of severe pneumonia (risk around 16 %) with sometimes lethal issue.Fetal complications: before 24 weeks of gestation (WG), transmission to the foetus can lead to severe condition in about 2 % cases. Congenital Varicella Syndrome associates cutaneous lesions, muscular atrophy, central nervous system lesions and disseminated visceral infection. Fetal infection can also lead to early tester manifestation in the newborn (3 %), or to asymptomatic infection (3 %). Molecular analysis of the amniotic fluid with PCR can lead to a prenatal diagnosis. Peripartum infection, with maternal eruption between 5 days before and 2 days after delivery, can induce in 25 % of neonatal infection in the infants with an increased risk of severe or lethal infection. Maternal tester during pregnancy does not lead to an increased risk of fetal malformation.

Prenatal DiagnosisVolume 18, Issue 4 p. 407-409 Correspondence Letter. Prenatal diagnosis of congenital toxoplasmosis by PCR: extended experience F. Forestier, F. Forestier Service de Médecine et Biologie Foetales, Institut de Puériculture de Paris, 26 Boulevard Brune, 75014 Paris, FranceSearch for more papers by this authorP. Hohlfeld, Corresponding Author P. Hohlfeld Département de Gynécologie-Obstétrique, Centre Hospitalier Universitaire Vaudois, Av. Pierre Decker, CH-1011 Lausanne, SwitzerlandDépartement de Gynécologie-Obstétrique, Centre Hospitalier Universitaire Vaudois, Av. Pierre Decker, CH-1011 Lausanne, SwitzerlandSearch for more papers by this authorY. Sole, Y. Sole Service de Médecine et Biologie Foetales, Institut de Puériculture de Paris, 26 Boulevard Brune, 75014 Paris, FranceSearch for more papers by this authorF. Daffos, F. Daffos Service de Médecine et Biologie Foetales, Institut de Puériculture de Paris, 26 Boulevard Brune, 75014 Paris, FranceSearch for more papers by this author F. Forestier, F. Forestier Service de Médecine et Biologie Foetales, Institut de Puériculture de Paris, 26 Boulevard Brune, 75014 Paris, FranceSearch for more papers by this authorP. Hohlfeld, Corresponding Author P. Hohlfeld Département de Gynécologie-Obstétrique, Centre Hospitalier Universitaire Vaudois, Av. Pierre Decker, CH-1011 Lausanne, SwitzerlandDépartement de Gynécologie-Obstétrique, Centre Hospitalier Universitaire Vaudois, Av. Pierre Decker, CH-1011 Lausanne, SwitzerlandSearch for more papers by this authorY. Sole, Y. Sole Service de Médecine et Biologie Foetales, Institut de Puériculture de Paris, 26 Boulevard Brune, 75014 Paris, FranceSearch for more papers by this authorF. Daffos, F. Daffos Service de Médecine et Biologie Foetales, Institut de Puériculture de Paris, 26 Boulevard Brune, 75014 Paris, FranceSearch for more papers by this author First published: 04 December 1998 https://doi.org/10.1002/(SICI)1097-0223(199804)18:4<407::AID-PD259>3.0.CO;2-7Citations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume18, Issue4April 1998Pages 407-409 RelatedInformation

Fetal and neonatal thrombocytopenia can be induced by a maternal alloimmunization against fetal platelet antigens. Alloimmune thrombocytopenia occurs with an incidence of 1/1,000 livebirths and may present either with evidence of damage from a prenatal hemorrhage such as porencephaly or intrauterine death, or with active life-threatening bleeding during the neonatal period. It is due to the destruction of fetal platelets by alloantibodies reacting on specific antigenic sites. In Caucasians, the human platelet antigen 1a (HPA-1a) is the most frequently involved in alloimmune thrombocytopenias, accounting for 80–90% of the cases. Anti-HPA-5b is responsible for a further 5–15% of the cases. This article reviews the clinical aspects, the biological diagnosis and the management, including prenatal sampling and maternal therapy.

Using fetal blood sampling, the diagnosis of triploidy can be strongly suspected on the basis of the peculiar hematological picture. Triploid fetuses present with anemia, marked anisopoikilocytosis, and grossly increased mean corpuscular volume, associated with thrombocytopenia and significant platelet anisocytosis. These findings are of considerable immediate diagnostic value. They allow physicians to immediately counsel parents about the prognosis of the fetus. In case of fetal or neonatal distress, this information could orientate decisions about obstetrical and pediatric management while waiting for the definitive diagnosis.

Fetal blood sampling is a widely used technique for both diagnostic and therapeutic purposes. However, despite the fact that examination of blood smears is a critical step in the study of a large variety of disorders, the place of fetal blood smears analysis has been overshadowed by more sophisticated diagnostic tools such as those offered by molecular biology. Nevertheless, as highlighted by four cases presented in this paper, the role of fetal blood smears examination must be re‐emphasized. The recognition of abnormal cytological findings limits the number of possible aetiologies, thus elegantly contributing to the diagnosis without multiplying unnecessary test techniques.

In a retrospective study of 3,129 fetal blood samples, we first determined normal values for gammaglutamyl transferase (GGT) activity and found 33 cases with a mean GGT level of 961.8 U/l (prevalence 1.05%) corresponding to more than 10-fold normal values. In such extreme cases, elevations of GGT activity in fetal blood have been poorly studied. The goal of this work was to correlate this highly abnormal biological finding with pathological fetal conditions and try to better understand the pathophysiological mechanisms. The most frequent underlying disorders were infections (n = 11), renal or bowel malformations (n = 12) and genetic abnormalities (n = 5). Two cases of cystic fibrosis and one case of fetal alcohol syndrome were also encountered. In another 2 cases, no explanation was found.

The recent development of routine automated plate let counts has revealed the frequency of thrombocytope nia in pregnant women. This is not simply a biologic curiosity: thrombocytopenia can be an important sign of a developing problem in the woman or her fetus

Normal levels of cancer-associated antigen (CA) 19-9, neurone-specific enolase (NSE), cancer-associated antigen (CA) 125, and mucin-like carcinoma-associated antigen (MCA) during pregnancy were determined in 87 mothers and fetuses, using a solid-phase sandwich enzyme immunoassay. CA 19-9 concentrations were higher in the fetuses, whereas the other three tumour-associated antigen levels were higher in the mothers. Only fetal NSE and MCA levels were positively correlated with those in maternal serum. Contrary to adult samples, no difference was demonstrated between male and female fetal levels of CA 125. MCA was the only maternal marker that increased significantly with gestational age between 20 and 34 weeks' pregnancy.

Fetal platelet counts were retrospectively studied in a series of 5,194 consecutive fetal blood samplings (FBS). The mean value was 245 +/- 65 x 10(9)/L, without significant variation between 17 and 41 weeks' gestation. After exclusion of false thrombocytopenia due to contamination with amniotic fluid, 247 fetuses had platelet counts less than 150 x 10(9)/L. In 70 cases, thrombocytopenia was due to congenital infectious diseases (toxoplasmosis, rubella, and cytomegalovirus). It was related to immune causes in 45 cases: anti-HPA-1a (n = 23), anti- HPA-5b (n = 2) or possible anti-HLA (n = 2) alloimmunizations, and immune thrombocytopenic purpura (n = 18). Chromosomal abnormality was the etiology in 43 cases (trisomy 13, 18, and 21, Turner's syndrome, triploidy), and other disorders (multiple birth defects, intrauterine growth retardation, rhesus disease, and gestational thrombocytopenia) in 62 cases. No specific cause for the low platelet count could be established in 27 fetuses (range, 115 to 149 x 10(9)/L). Severe thrombocytopenia (< or = 50 x 10(9)/L) occurred mainly in immune cases (16%), congenital infectious diseases (7%), and chromosomal abnormalities (1%). Diagnosis, prognosis, and management of fetal thrombocytopenia are presented in the different clinical situations. In this series, FBS was never associated with serious bleeding, and no fetal exsanguination was observed.

BACKGROUND Congenital infection with Toxoplasma gondii can produce serious sequelae. However, there is little consensus about screening during pregnancy, and the tests used to establish a prenatal diagnosis of toxoplasmosis are complex and slow. We evaluated a simpler approach that is based on a polymerase-chain-reaction (PCR) test. METHODS Prenatal diagnostic tests, including ultrasonography, amniocentesis, and fetal-blood sampling, were performed in 2632 women with T. gondii infection acquired during pregnancy. In 339 consecutive women, a competitive PCR test for T. gondii was performed on amniotic fluid, and its results were compared with those of conventional diagnostic tests. The PCR test targets the B1 gene of T. gondii, uses an internal control, and can be completed in a day. Positive tests were confirmed by serologic testing of newborns or by autopsy in terminated pregnancies. RESULTS Overall, the risk of fetal infection was 7.4 percent, but it increased sharply with gestational age. Congenital infection was demonstrated in 34 of 339 fetuses by conventional methods, and the PCR test was positive in all 34. In three other fetuses, only the PCR test gave positive results, and follow-up testing confirmed the presence of congenital toxoplasmosis. The PCR test gave one false negative result but no false positive results. The PCR test performed better than conventional parasitologic methods (sensitivity, 97.4 vs. 89.5 percent; negative predictive value, 99.7 vs. 98.7 percent). CONCLUSIONS For the prenatal diagnosis of congenital T. gondii infection, an approach based on a PCR test performed on amniotic fluid is rapid, safe, and accurate.

Vox SanguinisVolume 67, Issue s3 p. 85-88 MANAGEMENT OF FETAL AND NEONATAL ALLOIMMUNE THROMBOCYTOPENIA CÉCILE KAPLAN, CÉCILE KAPLAN INTS, 6 rue Alexandre Cabanel - 75015 Paris, FRANCESearch for more papers by this authorFERNAND DAFFOS, FERNAND DAFFOS Institut de Puériculture, 26 bd Brune - 75014 Paris, FRANCESearch for more papers by this authorFRANÇOIS FORESTIER, FRANÇOIS FORESTIER Institut de Puériculture, 26 bd Brune - 75014 Paris, FRANCESearch for more papers by this authorMARIE-CHRISTINE MOREL-KOPP, MARIE-CHRISTINE MOREL-KOPP INTS, 6 rue Alexandre Cabanel - 75015 Paris, FRANCESearch for more papers by this authorGIL TCHERNIA, GIL TCHERNIA Centre Hospitalier de Bicètre, 78 rue du Gal Leclerc, 94275 Kremlin Bicètre, FRANCESearch for more papers by this author CÉCILE KAPLAN, CÉCILE KAPLAN INTS, 6 rue Alexandre Cabanel - 75015 Paris, FRANCESearch for more papers by this authorFERNAND DAFFOS, FERNAND DAFFOS Institut de Puériculture, 26 bd Brune - 75014 Paris, FRANCESearch for more papers by this authorFRANÇOIS FORESTIER, FRANÇOIS FORESTIER Institut de Puériculture, 26 bd Brune - 75014 Paris, FRANCESearch for more papers by this authorMARIE-CHRISTINE MOREL-KOPP, MARIE-CHRISTINE MOREL-KOPP INTS, 6 rue Alexandre Cabanel - 75015 Paris, FRANCESearch for more papers by this authorGIL TCHERNIA, GIL TCHERNIA Centre Hospitalier de Bicètre, 78 rue du Gal Leclerc, 94275 Kremlin Bicètre, FRANCESearch for more papers by this author First published: July 1994 https://doi.org/10.1111/j.1423-0410.1994.tb04550.xCitations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Fetal/neonatal immune thrombocytopenias result from increased platelet destruction by maternal antiplatelet antibodies. There is a risk of intracerebral haemorrhage and therefore of neurological impairment or death during the thrombocytopenic period, especially if a defective platelet function co-exists. As no maternal parameter is predictive of the fetal platelet count, the only reliable assessment of the fetal status depends on the fetal blood sampling. Only in case of materno-fetal alloimmunisation the therapy initiated to reverse fetal thrombocytopenia was shown to be effective, but the optimal mode of antenatal treatment is currently under study As the neonatal therapy and the management of subsequent pregnancies are somehow different it is mandatory to make the distinction between the auto or allo-origin of the fetal thrombocytopenia. The definition of high risk pregnancies will be of help for the development of a routine screening program.