30 research outputs found
Cerebral MRI on fetuses submitted to repeated cocaine administration during the gestation: an ovine model
The aim of this study was to determine the role of Magnetic Resonance Imaging (MRI) in investigating fetal cerebral lesions induced by long term exposure to cocaine during sheep pregnancy. Cerebral Magnetic Resonance Imaging was performed on two groups of fetuses at 125 days of gestation (normal gestation: 145 days). The control group consisted of eight fetuses of four pregnant ewes. The study group consisted of eight fetuses of four pregnant ewes receiving daily 140 mg/kg injection of cocaine from day 60 until delivery. The following MR sequences were applied: T1-weighted FLASH, and T2-weighted Fast-Spin-Echo. Cerebral images were evaluated semi quantitatively using the following criteria: Heterogenicity, contrast between grey and white matter, contours irregularity, hyposignal, lateral ventricle sizes. The brightness distribution and homogenicity of the images were analysed by means of edge pair distributions using a new computerized method originally designed for ultrasound images analysis developed by Ultrasight inc (USA). (1) Flash T1: Heterogenic areas and irregular contours were more frequent in cocaine exposed fetuses. The contrast between grey and white matter was more important in the cocaine group. Hyposignal was found only in the cocaine group. Enlarged lateral ventricle occurred more frequently in the cocaine group. (2) Spin echo T2: The contrast between grey and white matter was higher and the contours of the brain more irregular in the cocaine group. Heterogenicity and hyposignal were also more frequent in this group but the difference with the control group was not significant. The computerized analysis of the contrast density on the cerebral images showed that 88% of the areas exceeding the reference level concerned the cocaine group, while only 14% of the areas exceeding the reference level concerned the control group. Long term exposure to cocaine induces cerebral tissue modifications, in favor of an advanced maturation and the development of hypoxic lesions. The histology of the brains confirmed in the cocaine group, the existence of hypoxic lesions with gliosis, perivascular edema and hemorrhages, and neuronal death
Reproductive experience of women living with phenylketonuria
Introduction: Many women with PKU are well-informed about the risks of maternal PKU but there are several barriers to achieving satisfactory metabolic control before and during pregnancy. Many studies have documented the outcome of maternal PKU infants, but very little has been reported about the experiences of women of reproductive age with PKU, particularly about their psychosexual development, pre-conception, pregnancy and postnatal experience.
Methods: In the UK, in a subsection of an online questionnaire conducted by the National Society for PKU (NSPKU) about living with PKU, women aged 18 years and over completed 9 closed questions about their pre-conception, pregnancy and post-natal experiences and an open-ended question on their reproductive health.
Results: 300 women aged 18 years and over with PKU completed this questionnaire with 37% (n= 111/300) of women already having children. 56% (n= 71/128) of pregnancies were planned and a further 18% (n= 23/128) of women had both planned and unplanned pregnancies. Most women (73%, n=200/273) expressed concerns, fears and distress about pregnancy and two thirds of women who had at least one pregnancy stated that having PKU made pregnancy more stressful and difficult. 60% (n= 164/273) were concerned that they may cause harm to a baby, 58% (n= 159/273) worried about their ability to manage a strict diet during pregnancy, 54% (n= 147/273) had anxiety about their ability to maintain blood Phe within target range, and 48% (n= 132/273) feared having an unplanned pregnancy.
Postnatally, 48% (n= 45/93) had low mood or sadness, 42% (n= 38/93) were depressed, 34% (n= 32/93) felt unable to cope, 33% (n= 31/93) said they could not manage their PKU and care for their baby, 14% (n= 13/93) struggled with child care needs and 4% (n= 4/94) worried they might hurt themselves or their baby through being unable to manage their diet.
Conclusions: Many women with PKU have unmet sexual and reproductive health needs Pregnancy fears are prominent from adolescence onwards and for some women overarching concerns about their ability to cope with pregnancy led to a decision not to have children. Interventions are needed to reduce the psychological impact of the risk of maternal PKU syndrome and assist with safe pregnancies. Post-natal experiences of women with PKU give rise to concern
A proteasome-resistant fragment of NIK mediates oncogenic NF-ΞΊB signaling in schwannomas
Schwannomas are common, highly morbid and medically untreatable tumors that can arise in patients with germ line as well as somatic mutations in neurofibromatosis type 2 (NF2). These mutations most commonly result in the loss of function of the NF2-encoded protein, Merlin. Little is known about how Merlin functions endogenously as a tumor suppressor and how its loss leads to oncogenic transformation in Schwann cells (SCs). Here, we identify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ΞΊB)-inducing kinase (NIK) as a potential drug target driving NF-ΞΊB signaling and Merlin-deficient schwannoma genesis. Using a genomic approach to profile aberrant tumor signaling pathways, we describe multiple upregulated NF-ΞΊB signaling elements in human and murine schwannomas, leading us to identify a caspase-cleaved, proteasome-resistant NIK kinase domain fragment that amplifies pathogenic NF-ΞΊB signaling. Lentiviral-mediated transduction of this NIK fragment into normal SCs promotes proliferation, survival, and adhesion while inducing schwannoma formation in a novel in vivo orthotopic transplant model. Furthermore, we describe an NF-ΞΊB-potentiated hepatocyte growth factor (HGF) to MET proto-oncogene receptor tyrosine kinase (c-Met) autocrine feed-forward loop promoting SC proliferation. These innovative studies identify a novel signaling axis underlying schwannoma formation, revealing new and potentially druggable schwannoma vulnerabilities with future therapeutic potential
ΠΠΎΠΆΠ»ΠΈΠ²ΠΎΡΡΡ ΡΠ»ΡΡΡΠ°Π·Π²ΡΠΊΠΎΠ²ΠΎΡ Π΄ΡΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Ρ ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΠΎΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΡΡ
Π£ ΡΡΠ°ΡΡΡ Π΄Π»Ρ ΠΎΡΡΠ½ΠΊΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΠΎΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΡΡ Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΡΡΡ ΡΠ»ΡΡΡΠ°Π·Π²ΡΠΊΠΎΠ²Ρ ΠΌΠ°ΡΠΊΠ΅ΡΠΈ β ΠΊΠΎΠΌΡΡΠ½ΠΈΠΉ ΠΏΡΠΎΡΡΡΡ. ΠΡΠ°ΡΠΈΠΉ ΡΠ΅ΡΠΌΡΠ½ Π²Π°Π³ΡΡΠ½ΠΎΡΡΡ Π΄Π»Ρ Π²ΠΈΠΌΡΡΡΠ²Π°Π½Π½Ρ ΠΊΠΎΠΌΡΡΡΠ΅Π²ΠΎΠ³ΠΎ ΠΏΡΠΎΡΡΠΎΡΡ ΠΏΠ»ΠΎΠ΄ΡΠ² Ρ Π²ΡΠ΄ 11 ΡΠΈΠΆΠ½ΡΠ² Π΄ΠΎ 13 ΡΠΈΠΆΠ½ΡΠ² 6 Π΄Π½ΡΠ². ΠΠ°ΠΉΠΌΠ΅Π½ΡΠ° ΠΊΡΠΏΡΠΈΠΊΠΎΠ²ΠΎ-ΡΡΠΌ'ΡΠ½Π° Π΄ΠΎΠ²ΠΆΠΈΠ½Π° ΠΏΠΎΠ²ΠΈΠ½Π½Π° Π±ΡΡΠΈ 45 ΠΌΠΌ, Π° ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½Π° β 84 ΠΌΠΌ. ΠΡΠΎΡΠ²ΠΈ Π·Π±ΡΠ»ΡΡΠ΅Π½ΠΎΠ³ΠΎ ΠΏΠΎΡΠΈΠ»ΠΈΡΠ½ΠΎΠ³ΠΎ Π½Π°ΠΊΠΎΠΏΠΈΡΠ΅Π½Π½Ρ ΡΡΠ΄ΠΈΠ½ΠΈ Π² ΠΏΠ»ΠΎΠ΄ΡΠ² ΡΠ· Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΠΈΠΌΠΈ Π°Π½ΠΎΠΌΠ°Π»ΡΡΠΌΠΈ Π·ΠΌΠ΅Π½ΡΡΡΡΡΡΡ ΠΏΡΡΠ»Ρ 13 ΡΠΈΠΆΠ½ΡΠ², ΡΠ°ΡΡΠΎΡΠ° ΠΏΡΠ°Π²ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ Π²ΠΈΠΌΡΡΡ Π·ΠΌΠ΅Π½ΡΡΡΡΡΡΡ ΠΏΡΡΠ»Ρ 13 ΡΠΈΠΆΠ½ΡΠ², ΠΎΡΠΊΡΠ»ΡΠΊΠΈ ΠΏΠ»ΡΠ΄ ΠΏΡΠΈΠΉΠΌΠ°Ρ Π²Π΅ΡΡΠΈΠΊΠ°Π»ΡΠ½Π΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Π½Ρ, ΡΠΎ ΡΡΠΊΠ»Π°Π΄Π½ΡΡ ΠΎΡΡΠΈΠΌΠ°Π½Π½Ρ ΠΏΠΎΡΡΡΠ±Π½ΠΎΠ³ΠΎ Π·ΠΎΠ±ΡΠ°ΠΆΠ΅Π½Π½Ρ
Reproductive experience of women living with phenylketonuria
Introduction: Many women with PKU are well-informed about the risks of maternal PKU but there are several barriers to achieving satisfactory metabolic control before and during pregnancy. Many studies have documented the outcome of maternal PKU infants, but very little has been reported about the experiences of women of reproductive age with PKU, particularly about their psychosexual development, pre-conception, pregnancy and postnatal experience.
Methods: In the UK, in a subsection of an online questionnaire conducted by the National Society for PKU (NSPKU) about living with PKU, women aged 18 years and over completed 9 closed questions about their pre-conception, pregnancy and post-natal experiences and an open-ended question on their reproductive health.
Results: 300 women aged 18 years and over with PKU completed this questionnaire with 37% (n= 111/300) of women already having children. 56% (n= 71/128) of pregnancies were planned and a further 18% (n= 23/128) of women had both planned and unplanned pregnancies. Most women (73%, n=200/273) expressed concerns, fears and distress about pregnancy and two thirds of women who had at least one pregnancy stated that having PKU made pregnancy more stressful and difficult. 60% (n= 164/273) were concerned that they may cause harm to a baby, 58% (n= 159/273) worried about their ability to manage a strict diet during pregnancy, 54% (n= 147/273) had anxiety about their ability to maintain blood Phe within target range, and 48% (n= 132/273) feared having an unplanned pregnancy.
Postnatally, 48% (n= 45/93) had low mood or sadness, 42% (n= 38/93) were depressed, 34% (n= 32/93) felt unable to cope, 33% (n= 31/93) said they could not manage their PKU and care for their baby, 14% (n= 13/93) struggled with child care needs and 4% (n= 4/94) worried they might hurt themselves or their baby through being unable to manage their diet.
Conclusions: Many women with PKU have unmet sexual and reproductive health needs Pregnancy fears are prominent from adolescence onwards and for some women overarching concerns about their ability to cope with pregnancy led to a decision not to have children. Interventions are needed to reduce the psychological impact of the risk of maternal PKU syndrome and assist with safe pregnancies. Post-natal experiences of women with PKU give rise to concern
Imaging fetal anatomy.
Due to advancements in ultrasound techniques, the focus of antenatal ultrasound screening is moving towards the first trimester of pregnancy. The early first trimester however remains in part, a 'black box', due to the size of the developing embryo and the limitations of contemporary scanning techniques. Therefore there is a need for images of early anatomical developmental to improve our understanding of this area. By using new imaging techniques, we can not only obtain better images to further our knowledge of early embryonic development, but clear images of embryonic and fetal development can also be used in training for e.g. sonographers and fetal surgeons, or to educate parents expecting a child with a fetal anomaly. The aim of this review is to provide an overview of the past, present and future techniques used to capture images of the developing human embryo and fetus and provide the reader newest insights in upcoming and promising imaging techniques. The reader is taken from the earliest drawings of da Vinci, along the advancements in the fields of in utero ultrasound and MR imaging techniques towards high-resolution ex utero imaging using Micro-CT and ultra-high field MRI. Finally, a future perspective is given about the use of artificial intelligence in ultrasound and new potential imaging techniques such as synchrotron radiation-based CT to increase our knowledge regarding human development
Mitochondrial DNA content and methylation in fetal cord blood of pregnancies with placental insufficiency
Introduction:
Intrauterine growth restriction (IUGR) and preeclampsia (PE) are pregnancy disorders characterized by placental insufficiency with oxygen/nutrient restriction and oxidative stress, all influencing mitochondria functionality and number. Moreover, IUGR and PE fetuses are predisposed to diseases later in life, and this might occur through epigenetic alterations.
Here we analyze content and methylation of mitochondrial DNA (mtDNA), for the first time in IUGR and PE singleton fetuses, to identify possible alterations in mtDNA levels and/or epigenetic control of mitochondrial loci relevant to replication (D-loop) and functionality (mt-TF/RNR1: protein synthesis, mt-CO1: respiratory chain complex).
Methods:
We studied 35 term and 8 preterm control, 31 IUGR, 17 PE/IUGR and 17 PE human singleton pregnancies with elective cesarean delivery. Fetal cord blood was collected and evaluated for biochemical parameters. Extracted DNA was subjected to Real-time PCR to assess mtDNA content and analyzed for D-loop, mt-TF/RNR1 and mt-CO1 methylation by bisulfite conversion and pyrosequencing.
Results:
mtDNA levels were increased in all pathologic groups compared to controls. Mitochondrial loci showed very low methylation levels in all samples; D-loop methylation was further decreased in the most severe cases and associated to umbilical vein pO2. mt-CO1 methylation levels inversely correlated to mtDNA content.
Discussion:
Increased mtDNA levels in IUGR, PE/IUGR and PE cord blood may denote a fetal response to placental insufficiency. Hypomethylation of D-loop, mt-TF/RNR1 and mt-CO1 loci confirms their relevance in pregnancy