Showing papers by "Oriol Coll published in 2017"

Placental Mitochondrial Toxicity, Oxidative Stress, Apoptosis, and Adverse Perinatal Outcomes in HIV Pregnancies Under Antiretroviral Treatment Containing Zidovudine.

Abstract: OBJECTIVE To determine whether mitochondrial, oxidative, and apoptotic abnormalities in placenta derived from HIV and combined antiretroviral therapy (cART) containing zidovudine (AZT) could be associated with adverse perinatal outcome. DESIGN Cross-sectional, controlled, observational study. METHODS We studied obstetric results and mitochondrial, oxidative, and apoptotic state in placenta of 24 treated HIV-infected and 32 -uninfected pregnant women. We measured mitochondrial DNA (mtDNA) content by quantitative reverse transcriptase-polymerase chain reaction (mtND2/n18SrRNA), oxidative stress by the spectrophotometric quantification of lipid peroxidation and apoptosis by Western blot analysis of active caspase-3 respect to β-actin content and analysis of the terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS Global adverse perinatal outcome (defined as preterm delivery or/and small newborns for gestational age) was significantly increased in HIV pregnancies [or 6.7 (1.3-33.2); P < 0.05]. mtDNA content in HIV-infected women was significantly depleted (39.20% ± 2.78%) with respect to controls (0.59 ± 0.03 vs. 0.97 ± 0.07; P < 0.001). A significant 29.50% ± 9.14% increase in oxidative stress was found in placentas of HIV-infected women (23.23 ± 1.64 vs. 17.94 ± 1.03; P < 0.01). A trend toward 41.18% ± 29.41% increased apoptosis active caspase-3/β-actin was found in HIV patients (0.48 ± 0.10 vs. 0.34 ± 0.05; P = not significant), confirmed by transferase dUTP nick end labeling assay. Adverse perinatal outcome did not correlate mitochondrial, oxidative, or apoptotic findings. CONCLUSIONS Placentas of HIV-infected pregnant women under AZT cART showed evidence of mtDNA depletion, increased oxidative stress levels, and apoptosis suggestive of secondary mitochondrial failure, potential base of associated adverse perinatal outcome. Despite the fact that further demonstration of causality would need new approaches and bigger sample sizes, AZT-sparing cART should be considered in the context of pregnancy.

Towards a New Strategy for Diagnosis of Congenital Trypanosoma cruzi Infection.

Abstract: The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial.

Abstract: Objective: To study whether knowledge of cervical length (CL) is useful in reducing the length of hospital stay in women admitted because of threatened preterm la

Mitochondrial toxicity and caspase activation in HIV pregnant women.

Abstract: To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14–20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naive participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase-3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV-pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV-infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti-retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size.

Lower endometrial receptivity in HIV-infected women receiving oocyte donation: a comorbidity of HIV infection?

Abstract: STUDY QUESTION Are the reproductive outcomes of HIV-infected donor oocyte recipient women comparable to those of non-infected women? SUMMARY ANSWER HIV-infected women have lower clinical pregnancy and live birth rates than non-infected women. WHAT IS ALREADY KNOWN The literature on the effect of HIV infection on reproductive outcome is scarce at best; the only report to date comparing oocyte donation cycles in HIV-infected women versus non-infected controls found no differences in pregnancy rates between the two groups. However, this study was performed nearly a decade ago and did not evaluate the effect of immuno-virological characteristics of oocyte recipients or the HIV antiretroviral therapy effect. STUDY DESIGN SIZE AND DURATION This is a matched-cohort study including 514 oocyte donation cycles, 257 from HIV-infected women and 257 non-infected controls, performed between April 2004 and November 2014. PARTICIPANTS/MATERIALS SETTING AND METHOD Each cycle of an HIV-infected woman (n = 257) was matched with a cycle of a non-infected woman (1:1). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy and live birth in the two groups were compared using a multivariate logistic regression analysis. The effect of antiretroviral treatment options on pregnancy outcomes of HIV-infected women was analyzed using a logistic regression model adjusted for time elapsed from diagnosis, and CD4 levels and viral load prior to embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE Cycles of HIV-infected patients receiving oocyte donation presented lower pregnancy and live birth rates than matched non-infected controls. Treatment options and infection parameters analyzed do not seem to affect the reproductive results in HIV-infected women. The variable most influencing pregnancy outcomes was the number of transferred embryos; lower pregnancy rates were obtained after single embryo transfer. LIMITATIONS REASONS FOR CAUTION Patients with HIV infection have specific health issues, such as infection/treatment side effects, which makes it impossible to find a matching control group of non-infected patients for these variables. WIDER IMPLICATIONS OF THE FINDINGS HIV-infected women receiving donated oocytes present lower pregnancy rates when compared to non-infected controls, regardless of the antiretroviral treatment followed. The complexity of the treatments (both in medication types and combinations) makes it difficult to define whether any one treatment option is better than the others in terms of pregnancy outcomes in oocyte recipients. STUDY FUNDING/COMPETING INTERESTS None. TRIAL REGISTRATION NUMBER Not applicable.