Regulation of interleukin-6 fetoplacental levels could be involved in the protective effect of low-molecular weight heparin treatment on murine spontaneous abortion.

PROBLEM: CBA/J x DBA/2 abortion rate could be the consequence of a deficient local production of T helper (Th2) cytokines, which cause fetal wastage via fgl2 prothrombinase. Heparin reduces significantly the abortion rate in mice and recurrent spontaneous abortion (RSA) patients. We proposed to determine the effect of enoxaparin on the levels of local interleukin (IL)-6 during murine pregnancy. METHOD OF STUDY: Recombinant human IL-6 (rhIL-6) or enoxaparin were inoculated in CBA/J x DBA/2 pregnant mice on days 6.5-12.5. IL-6 levels in sera as well as in culture supernatants of day 9.5 fetoplacental units of CBA/J x BALB/c control mice or CBA/J x DBA/2 abortion combination were determined by enzyme-linked immunosorbent assay (ELISA) test. RESULTS: CBA/J x DBA/2 fetoplacental units secreted significantly lower levels of IL-6 with regard to CBA/J x BALB/c normal units. rhIL-6h and enoxaparin treatments decreased the resorption rate and regulated IL-6 fetoplacental levels. CONCLUSION: This study suggests that regulation of IL-6 fetoplacental levels could be involved in heparin-mediated anticoagulation protection against abortion.

Effect of ovaric hyper-stimulation on blood lymphocyte subpopulations, cytokines, leptin and nitrite among patients with unexplained infertility.

PROBLEM: To determine the effect of ovarian stimulation on TH1, TH2 and natural killer (NK) lymphocytes, plasma cytokines, leptin and nitrite levels. METHODS: Women with reproductive failure were studied during the implantation window, at baseline (n = 18) and under ovarian stimulation (gonadotropins + progesterone, n = 6). CONTROLS: eight fertile women. Lymphocyte subpopulations and NK function were determined by flow cytometry. Interleukin-2 (IL-2), IL-4, IL-10, IFN-gamma, TNF-alpha, TGF-beta1 and leptin were measured by enzyme immunoassay (EIA); nitrite by the Griess reaction. RESULTS: At baseline, patients had higher values of NK effectors, NK activity and plasma IFN-gamma and IL-2 than controls. Conversely, TGF-beta1 values were lower. Hormones induced leukocytosis. Under stimulation, THI CD4+ cells, NK effectors and function and plasma IFN-gamma and IL-2 decreased, while transforming growth factor (TGF)-beta1 increased. Other variables did not change. CONCLUSION: The abnormal distribution of leukocytes, high TH1 cytokines and a low TGF-beta1 associated with reproductive failure, respond to ovarian stimulation, achieving total or partial normalization.

[Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia]. / Tratamiento con enoxaparina adaptado a los programas de fertilidad en mujeres con aborto recurrente y trombofilia.

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85%) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85%) of the pregnancies ended in live birth versus 16/105 (15%) of the pregnancies without treatment (p < 0.001). These results suggest that enoxaparin adapted to the fertility program can be effective in the prevention of preclinical and clinical abortion in women with thrombophilia.

Tratamiento con enoxaparina adaptado a los programas de fertilidad en mujeres con aborto recurrente y trombofilia. / [Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia]

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85

) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85

) of the pregnancies ended in live birth versus 16/105 (15

) of the pregnancies without treatment (p < 0.001). These results suggest that enoxaparin adapted to the fertility program can be effective in the prevention of preclinical and clinical abortion in women with thrombophilia.

[Hypofibrinolysis and other hemostatic defects in women with antecedents of early reproductive failure]. / Hipofibrinolisis y otros defectos de la hemostasia en mujeres con antecedentes de fallas reproductivas tempranas.

The fibrinolytic system is involved in blood clot lysis and in other biological processes that require extracellular proteolysis such as ovulation, blastocyst implantation and trophoblastic invasion. An impaired fibrinolytic capacity is a common feature in women suffering from unexplained early recurrent pregnancy loss. We carried out a prospective study with 114 patients. Three groups were established: Group 1: women who had two or more unexplained miscarriages of < 12 weeks of gestation (n = 52). Group 2: women who had 2 or more embryo-implantation failure after embryo-transfer with good quality embryos in assisted reproduction (n = 46). Group 3: women who had 2 or more embryo-implantation failure after embryo-transfer and one early loss of a pregnancy achieved in a cycle of assisted reproduction (n = 16). Fibrinolytic pattern pre and post-occlusion test was carried out: ECLT, PAI-1i, PAI-1b, t-PAi, t-PAb. In addition other studies were performed: LAC, ACA IgG and IgM, fibrinogen, factor XII, APCR. A high prevalence of thrombophilic defects and hypofibrinolysis was observed in the three groups. The fibrinolytic pattern was similar in the three groups, although a prolonged pre occlusion ECLT was more frequent in women with primary infertility (Group 2). Isolated hypofibrinolysis was found in 50% of the patients. The remaining patients with hypofibrinolysis presented combined defects with LAC, ACA and abnormal APCR. The fibrinolytic pattern in women with or without antiphospholipid antibodies was similar, although an elevated pre occlusion PAI-1i was more common in women without antiphospholipid antibodies. High prevalence of fibrinolytic abnormalities observed in women with unexplained early recurrent pregnancy loss and in women with repeated failure implantation after embryo-transfer in assisted reproduction, suggests that hypofibrinolysis could be a parameter of early reproductive failure.

Hipofibrinolisis y otros defectos de la hemostasia en mujeres con antecedentes de fallas reproductivas tempranas. / [Hypofibrinolysis and other hemostatic defects in women with antecedents of early reproductive failure]

The fibrinolytic system is involved in blood clot lysis and in other biological processes that require extracellular proteolysis such as ovulation, blastocyst implantation and trophoblastic invasion. An impaired fibrinolytic capacity is a common feature in women suffering from unexplained early recurrent pregnancy loss. We carried out a prospective study with 114 patients. Three groups were established: Group 1: women who had two or more unexplained miscarriages of < 12 weeks of gestation (n = 52). Group 2: women who had 2 or more embryo-implantation failure after embryo-transfer with good quality embryos in assisted reproduction (n = 46). Group 3: women who had 2 or more embryo-implantation failure after embryo-transfer and one early loss of a pregnancy achieved in a cycle of assisted reproduction (n = 16). Fibrinolytic pattern pre and post-occlusion test was carried out: ECLT, PAI-1i, PAI-1b, t-PAi, t-PAb. In addition other studies were performed: LAC, ACA IgG and IgM, fibrinogen, factor XII, APCR. A high prevalence of thrombophilic defects and hypofibrinolysis was observed in the three groups. The fibrinolytic pattern was similar in the three groups, although a prolonged pre occlusion ECLT was more frequent in women with primary infertility (Group 2). Isolated hypofibrinolysis was found in 50

of the patients. The remaining patients with hypofibrinolysis presented combined defects with LAC, ACA and abnormal APCR. The fibrinolytic pattern in women with or without antiphospholipid antibodies was similar, although an elevated pre occlusion PAI-1i was more common in women without antiphospholipid antibodies. High prevalence of fibrinolytic abnormalities observed in women with unexplained early recurrent pregnancy loss and in women with repeated failure implantation after embryo-transfer in assisted reproduction, suggests that hypofibrinolysis could be a parameter of early reproductive failure.

[Physiopathology of preeclampsia]. / Fisiopatologia de la preeclampsia.

Preeclampsia is a disease which appears only during pregnancy. It is highly widespread, and in the underdeveloped countries is the leading cause of maternal mortality. Nowadays it is considered a disease originated in the activation of the vascular endothelium triggered by placental ischemia. The latter is produced by a defect in the trophoblastic invasion of the spiral arteries of the uterus. Genetic, immunologic and biochemical causes have been postulated in the attempt to explain this defect in the trophoblastic implant, but whatever the cause, the endothelial activation produces several chemical mediators affecting the function of all organs, and then generating preeclampsia related syndromes. The prevention of this disease occupies a special place in research and there are numerous trials with aspirin and calcium being developed at the moment.

Photorefractive processing for large adaptive phased arrays.

An adaptive null-steering phased-array optical processor that utilizes a photorefractive crystal to time integrate the adaptive weights and null out correlated jammers is described. This is a beam-steering processor in which the temporal waveform of the desired signal is known but the look direction is not. The processor computes the angle(s) of arrival of the desired signal and steers the array to look in that direction while rotating the nulls of the antenna pattern toward any narrow-band jammers that may be present. We have experimentally demonstrated a simplified version of this adaptive phased-array-radar processor that nulls out the narrow-band jammers by using feedback-correlation detection. In this processor it is assumed that we know a priori only that the signal is broadband and the jammers are narrow band. These are examples of a class of optical processors that use the angular selectivity of volume holograms to form the nulls and look directions in an adaptive phased-array-radar pattern and thereby to harness the computational abilities of three-dimensional parallelism in the volume of photorefractive crystals. The development of this processing in volume holographic system has led to a new algorithm for phased-array-radar processing that uses fewer tapped-delay lines than does the classic time-domain beam former. The optical implementation of the new algorithm has the further advantage of utilization of a single photorefractive crystal to implement as many as a million adaptive weights, allowing the radar system to scale to large size with no increase in processing hardware.

Wide angular aperture holograms in photorefractive crystals by the use of orthogonally polarized write and read beams.

We demonstrate a method of simultaneous holographic recording and readout in photorefractive crystals that provides high write-read beam isolation and wide angular bandwidth. The method uses orthogonally polarized read and write beams and parallel tangent diffraction geometry near the equal curvature condition to provide spatially separable, orthogonally polarized diffracted output beams with high isolation and wide Bragg-matched angular bandwidth. The available angular bandwidth of this read-write technique is analyzed, simulated, and experimentally investigated. The measured angular bandwidth internal to the crystal is approximately 18° × 6° for our 45°-cut BaTiO(3) crystal, yet the entire hologram still demonstrates high Bragg selectivity. In contrast, traditional nonparallel-tangent geometries yield angular apertures of the order of 1° × 4°.

The effect of hypoglycemic sulfonylureas on human red blood cell transglutaminase activity.

We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity.

[Effect of tolbutamide on the activity of transglutaminase]. / Efecto de la tolbutamida sobre la actividad transglutaminasa.

Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity.