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1.
Dalton Trans ; 41(28): 8615-23, 2012 Jul 28.
Article in English | MEDLINE | ID: mdl-22678751

ABSTRACT

The in vivo(212)Pb/(212)Bi generator is promising for application in targeted alpha therapy (TAT) of cancer. One main limitation of its therapeutic application is due to potential release of (212)Bi from the radioconjugate upon radioactive decay of the mother nuclide (212)Pb, potentially leading to irradiation of healthy tissue. The objective of the present work is to assess whether the chelate CHX-A''-DTPA (N-(2-aminoethyl)-trans-1,2-diaminocyclohexane-N,N',N''-pentaacetic acid) bound to a biological carrier molecule may be able to re-complex released (212)Bi under in vivo conditions to limit its translocation from the target site. CHX-A''-DTPA was bound to bovine gamma globulin (BGG) to mimic a model conjugate and the stability of the Bi-CHX-A''-DTPA-BGG conjugate was studied in blood serum by ultrafiltration. TRLFS experiments using Cm(III) as a fluorescent probe demonstrated that linking CHX-A''-DTPA to BGG does not affect the coordination properties of the ligand. Furthermore, comparable stability constants were observed between Bi(III) and free CHX-A''-DTPA, BGG-bound CHX-A''-DTPA and DTPA. The complexation constants determined between Bi(III) and the chelate molecules are sufficiently high to allow ultra trace amounts of the ligand to efficiently compete with serum transferrin controlling Bi(III) speciation in blood plasma conditions. Nevertheless, CHX-A''-DTPA is not able to complex Bi(III) generated in blood serum because of the strong competition between Bi(III) and Fe(II) for the ligand. In other words, CHX-A''-DTPA is not "selective" enough to limit Bi(iii) release in the body when applying the (212)Pb/(212)Bi in vivo generator.


Subject(s)
Bismuth/blood , Chelating Agents/metabolism , Isothiocyanates/blood , Pentetic Acid/analogs & derivatives , Pentetic Acid/blood , Animals , Cattle , Edetic Acid/blood , Humans , In Vitro Techniques , gamma-Globulins/metabolism
2.
Hum Reprod ; 21(8): 2131-5, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16644913

ABSTRACT

BACKGROUND: It is conceivable that defective embryo hatching plays a part in the mechanisms involved in the decrease of embryo implantation rates with advancing age. In an effort to test this hypothesis, we tested the effectiveness of assisted hatching (AH) in women > or =37 years of age. METHODS: We prospectively studied 103 IVF-embryo transfer patients undergoing 103 embryo transfers. All of them were > or =37 years of age and had <3 previous IVF-embryo transfer attempts. Laser-AH of transferred embryos was either performed (AH group, n = 49) or not (control group, n = 54) according to randomized and double-blind methodology. Primary outcome was live birth rate. RESULTS: Population characteristics were comparable in AH and control groups as well as the mean number of embryos transferred (2.7 +/- 0.6 versus 2.7 +/- 0.6) and the prevalence of top quality embryos transferred (65 versus 59%, respectively). We failed to find any statistically significant difference between AH and control groups with regard to implantation (16.1 versus 16.7%, respectively) and live birth rates (22.4 versus 29.6%, respectively). CONCLUSION: The present study indicates that AH does not improve IVF-embryo transfer outcome in women aged > or =37 years.


Subject(s)
Embryo Implantation , Embryo Transfer , Laser Therapy , Maternal Age , Zona Pellucida , Adult , Double-Blind Method , Female , Humans , Pregnancy , Pregnancy Rate
3.
Hum Reprod ; 20(2): 420-4, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15528263

ABSTRACT

BACKGROUND: In vitro oocyte maturation (IVM) permits the use of immature oocytes in IVF. IVM does not require ovarian stimulation and so can be offered to patients at risk of ovarian hyperstimulation syndrome. METHODS: For this indication, we carried out 45 cycles of IVM in 33 women with polycystic ovarian syndrome (PCOS). RESULTS: A total of 509 cumulus-oocyte complexes was obtained; 276 (54.2%) oocytes matured in 24 h and 45 (8.8%) in 48 h. The normal fertilization (2PN) rate of oocytes matured in 24 and 48 h was 69.5 and 73.3% respectively. Among the 214 embryos obtained, 103 were transferred and 30 were frozen. Forty transfers were performed (2.5 embryos/transfer). Eleven women had a positive beta-hCG test (26.2% of pregnancies/puncture, 27.5% of pregnancies/transfer) and nine women had a clinical pregnancy (20.0% of pregnancies/puncture, 22.5% of pregnancies/transfer). Five babies have been born and one pregnancy is ongoing. Results of the clinical examination carried out at birth were normal. CONCLUSIONS: Our results show that IVM may be offered as an alternative to conventional IVF and to ovarian drilling in women with PCOS. The role of IVM in the therapeutic armamentarium for this condition should be further clarified.


Subject(s)
Fertilization in Vitro/methods , Infertility, Female/etiology , Infertility, Female/therapy , Ovary/cytology , Polycystic Ovary Syndrome/complications , Adult , Cryopreservation , Embryo Culture Techniques , Embryo Transfer , Female , France , Humans , Ovary/physiology , Ovulation , Pregnancy , Pregnancy Outcome
4.
J Gynecol Obstet Biol Reprod (Paris) ; 33(6 Pt 1): 518-24, 2004 Oct.
Article in French | MEDLINE | ID: mdl-15567968

ABSTRACT

OBJECTIVE: To evaluate the efficacy of semi natural cycle as option of treatment for the patients who have a poor prognosis to controlled ovarian hyperstimulation (COH). PATIENTS AND METHODS: Prospective study. Sixty-six patients with an ovulatory cycle who presented either altered ovarian status (AOS) or implantation failure (IMF) and had carried out a total of 133 semi natural IVF cycles were included. Once follicular dominance was established, the growth of this follicule was controlled by administration of the GnRH antagonist with exogenous gonadotrophins. RESULTS: Groups AOS (n = 47) and IMF (n = 19) were similar with regard to oocyte pickup rate (81.2% and 81.1%), the oocyte recovery rate (61.4% and 64.8%) and clinical pregnancies per oocyte pickups rate (15.4% and 16.6%), respectively. CONCLUSIONS: The semi natural cycle appears as option of treatment for patients who have a poor prognosis for successful in vitro fertilization.


Subject(s)
Chorionic Gonadotropin/therapeutic use , Fertilization in Vitro , Menstrual Cycle/physiology , Ovulation Induction/methods , Adult , Female , Follicular Phase , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Humans , Pregnancy , Pregnancy Rate , Prognosis , Prospective Studies
5.
Gynecol Obstet Fertil ; 31(12): 1030-5, 2003 Dec.
Article in French | MEDLINE | ID: mdl-14680784

ABSTRACT

OBJECTIVE: Couples with a risk of transmitting X-linked diseases included in a preimplantation genetic diagnosis (PGD) center need early and rapid fetal sex determination during pregnancy in two situations. The first situation corresponds to control of embryo sexing after PGD, the second one being that of couples in PGD program having a spontaneous pregnancy. Determination of fetal sex can be achieved by karyotyping using invasive procedures such as chorionic villus sampling (CVS), amniocentesis or cordocentesis and by non-invasive procedures such as ultrasound (US) examination. CVS is the earliest invasive procedure for fetal sex determination and molecular analysis of X-linked genetic disorders during the first trimester but it is associated with a risk of fetal loss. US allows reliable fetal sex determination only during the second trimester. Recently, reliable non-invasive fetal sex determination was realized by using SRY gene amplification in maternal serum. PATIENTS AND METHODS: We report the prospective use of fetal sex determination in maternal serum in our PGD center. Management of pregnancies was performed using this non-invasive procedure in four cases of embryo sexing control and nine cases of spontaneous pregnancies in couples included in PGD program for X-linked diseases. RESULTS: Fetal sex results using SRY gene amplification on maternal serum were in complete concordance with fetal sex observed by cytogenetic analysis or US examination, as well as at birth. DISCUSSION AND CONCLUSION: This new strategy allowed rapid sex determination during the first trimester and permitted to avoid performing invasive procedures in nine pregnancies.


Subject(s)
DNA/blood , Genes, sry , Genetic Diseases, X-Linked/diagnosis , Preimplantation Diagnosis , Sex Determination Analysis , Adult , Female , Fragile X Syndrome/diagnosis , Fragile X Syndrome/genetics , Genes, sry/genetics , Genetic Diseases, X-Linked/genetics , Humans , Male , Polymerase Chain Reaction/methods , Pregnancy , Pregnancy Trimester, First , Prospective Studies
6.
Reprod Biomed Online ; 6(4): 444-7, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12831591

ABSTRACT

A prospective randomized feasibility study was carried out on 10 patients undergoing IVF treatment using a single-dose LHRH antagonist protocol (cetrorelix, Cetrotide) with clomiphene citrate in combination with either human menopausal gonadotrophin (HMG) (n = 5) or recombinant human FSH (rFSH) (n = 5). Both treatment-groups, HMG and rFSH, were comparable with regard to age (33.2 +/- 2.6 versus 34.4 +/- 4.0 years) BMI (23.2 +/- 2.6 versus 22.7 +/- 1.6) and cause of infertility. They yielded comparable results concerning gonadotrophin dose (19.8 +/- 8.7 versus 17.0 +/- 8.9), stimulation days (6.5 +/- 2.0 versus 5.8 +/- 1.9) and live births (one versus two). No premature LH surge (LH >10 IU/ml and progesterone >1 ng/ml) occurred. The overall baby take-home rate was 30%. In a small number of patients, cetrorelix could be shown to effectively prevent premature LH surges in stimulation protocols combining clomiphene with gonadotrophins with an excellent baby take-home rate per started cycle of 30%.


Subject(s)
Clomiphene/administration & dosage , Fertility Agents, Female/administration & dosage , Fertilization in Vitro , Follicle Stimulating Hormone/administration & dosage , Gonadotropin-Releasing Hormone/administration & dosage , Hormone Antagonists/administration & dosage , Menotropins/administration & dosage , Adult , Drug Administration Schedule , Drug Combinations , Feasibility Studies , Female , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Hormones/administration & dosage , Humans
7.
Ecotoxicol Environ Saf ; 24(3): 294-300, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1282874

ABSTRACT

The toxicity of a copper-cadmium-ferbam mixture has been studied using the protozoan Colpidium campylum bioassay. The assays were designed according to the factorial experiments method, associated with multiple regression analysis. The results show that, at the concentrations tested, a synergy occurs between cadmium and ferbam, whereas the copper is only oligodynamic.


Subject(s)
Cadmium/toxicity , Copper/toxicity , Dimethyldithiocarbamate/toxicity , Eukaryota/drug effects , Fungicides, Industrial/toxicity , Animals , Drug Interactions , Drug Synergism , Eukaryota/growth & development
8.
Environ Pollut ; 65(3): 251-67, 1990.
Article in English | MEDLINE | ID: mdl-15092265

ABSTRACT

A copper-cadmium-nickel-zinc mixture was assessed in seven different river waters to study metal toxicity to the ciliate protozoan Colpidium campylum, the interactions occurring between metals, and the influence of the receiving water on toxicity. In the range of concentrations tested, which are representative of electroplating industry wastes, the main part of the toxicity can be attributed to copper and to cadmium-copper synergy. A classification of waters, based on a principal component analysis (PCA), was used to examine the main parameters of the water, which can affect the toxicity of metal mixtures. It appears that the mineralization of the water, more than the total organic carbon (TOC), is an important parameter for the expression of toxicity. A strategy for the estimation of ecotoxicological hazard assessment, based on a simplified factorial experiment is proposed. It enables one to study, in a two-step bioassay, the toxicity of an effluent, the influence of river water on its toxicity, and the effects of contact time and dilution. By applying PCA to data from very different waters, it may be possible to estimate the ecotoxicological risk associated with the discharge of an effluent, on the basis of the chemistry of the receiving water.

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