Intrauterine growth restriction - part 1.

PubMed

Sharma, Deepak; Shastri, Sweta; Farahbakhsh, Nazanin; Sharma, Pradeep

2016-12-01

Intrauterine growth restriction (IUGR) is a major and silent cause of various morbidity and mortality for the fetal and neonatal population. It is defined as a rate of fetal growth that is less than normal for the growth potential of that specific infant. The terms IUGR and small for gestational age (SGA) are often used interchangeably, although there exists subtle differences between the two. IUGR/SGA is an end result of various etiologies that includes maternal, placental and fetal factors and recently added genetic factors too, also contribute to IUGR. In this review article we will cover the antenatal aspect of IUGR and management with proven preventive intervention.

Effects and molecular mechanisms of intrauterine infection/inflammation on lung development.

PubMed

Pan, Jiarong; Zhan, Canyang; Yuan, Tianming; Wang, Weiyan; Shen, Ying; Sun, Yi; Wu, Tai; Gu, Weizhong; Chen, Lihua; Yu, Huimin

2018-05-10

Intrauterine infection/inflammation plays an important role in the development of lung injury and bronchopulmonary dysplasia (BPD) in preterm infants, While a multifactorial genesis is likely, mechanisms involved in BPD after intrauterine infection/inflammation are largely unknown. Recent studies have suggested microRNAs (miRNAs) are likely to play a role. Therefore, this study aimed to study the effects and mechanisms of intrauterine infection/inflammation on lung development, and to identify miRNAs related to lung injury and BPD. An animal model of intrauterine infection/inflammation was established with pregnant SD rats endocervically inoculated with E.coli. The fetal and neonatal rats were observed at embryonic day (E) 17, 19, 21 and postnatal day (P) 1, 3, 7, 14, respectively. Body weight, lung weight, the expression levels of NLRP3, TNF-α, IL-lβ, IL-6, VEGF, Collagen I, SP-A, SP-B and SP-C in the lung tissues of fetal and neonatal rats were measured. Expression profiles of 1218 kinds of miRNAs in the lungs of neonatal rats were detected by miRNA microarray technique. Target genes of the identified miRNAs were predicted through online software. Intrauterine infection/inflammation compromised not only weight development but also lung development of the fetal and neonatal rats. The results showed significantly increased expression of NLRP3, TNF-α, IL-1β, IL-6, Collagen I, and significantly decreased expression of VEGF, SP-A, SP-B and SP-C in the fetal and neonatal rat lung tissues in intrauterine infection group compared to the control group at different observation time point (P < 0.05). Forty-three miRNAs with significant differential expression were identified. Possible target genes regulated by the identified miRNAs are very rich. Intrauterine infection/inflammation results in lung histological changes which are very similar to those observed in BPD. Possible mechanisms may include NLRP3 inflammasome activation followed by inflammatory cytokines

Management of foetal asphyxia by intrauterine foetal resuscitation

PubMed Central

Velayudhareddy, S.; Kirankumar, H

2010-01-01

Management of foetal distress is a subject of gynaecological interest, but an anaesthesiologist should know about resuscitation, because he should be able to treat the patient, whenever he is directly involved in managing the parturient patient during labour analgesia and before an emergency operative delivery. Progressive asphyxia is known as foetal distress; the foetus does not breathe directly from the atmosphere, but depends on maternal circulation for its oxygen requirement. The oxygen delivery to the foetus depends on the placental (maternal side), placental transfer and foetal circulation. Oxygen transport to the foetus is reduced physiologically during uterine contractions in labour. Significant impairment of oxygen transport to the foetus, either temporary or permanent may cause foetal distress, resulting in progressive hypoxia and acidosis. Intrauterine foetal resuscitation comprises of applying measures to a mother in active labour, with the intention of improving oxygen delivery to the distressed foetus to the base line, if the placenta is functioning normally. These measures include left lateral recumbent position, high flow oxygen administration, tocolysis to reduce uterine contractions, rapid intravenous fluid administration, vasopressors for correction of maternal hypotension and amnioinfusion for improving uterine blood flow. Intrauterine Foetal Resuscitation measures are easy to perform and do not require extensive resources, but the results are encouraging in improving the foetal well-being. The anaesthesiologist plays a major role in the application of intrauterine foetal resuscitation measures. PMID:21189876

The importance of fetal gender in intrauterine growth restriction

PubMed Central

Radulescu, L; Ferechide, D; Popa, F

2013-01-01

One of the most important causes of perinatal mortality and morbidity complicating significant percentage pregnancies is intrauterine growth restriction (IUGR). Fetal growth restriction is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. Numerous studies in different populations reveal an association between intrauterine growth restriction and perinatal and postnatal developments, which differ according to the sex of newborns with intrauterine growth restriction. However, the mechanisms of intrauterine programming, the critical time necessary to cause injury and involvement of other factors are unclear and although several authors’ opinions differ, it seems that females are more likely to develop intrauterine growth restriction. Abbreviations: IUGR=intrauterine growth restriction PMID:23599816

Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study.

PubMed

Phillips, Sharon J; Hofler, Lisa G; Modest, Anna M; Harvey, Lara F B; Wu, Lily H; Hacker, Michele R

2017-07-01

Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intrauterine device, and whether women who continue using intrauterine devices differ from those who discontinue. We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ 2 tests and calculated hazard ratios using a multivariable Cox model. Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestrel intrauterine device and 32.6% for copper intrauterine device (P < .01), and at 5 years continuation rates were 28.1% for levonorgestrel intrauterine device and 23.8% for copper intrauterine device (P = .33). Black race, primiparity, and age were positively associated with discontinuation; education was not. The hazard ratio for discontinuation of levonorgestrel intrauterine device compared with copper intrauterine device >4 years was 0.71 (95% confidence interval, 0.55-0.93) and >5 years was 0.82 (95% confidence interval, 0.64-1.05) after adjusting for race, age, parity, and education. Copper intrauterine device users were more likely to experience expulsion (10.2% copper intrauterine device vs 4.9% levonorgestrel

Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study

PubMed Central

Phillips, Sharon J.; Hofler, Lisa G.; Modest, Anna M.; Harvey, Lara F. B.; Wu, Lily H.; Hacker, Michele R.

2018-01-01

Background Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intra-uterine device, and whether women who continue using intrauterine devices differ from those who discontinue. Objective We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. Study Design We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ2 tests and calculated hazard ratios using a multivariable Cox model. Results Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestrel intrauterine device and 32.6% for copper intrauterine device (P < .01), and at 5 years continuation rates were 28.1% for levonorgestrel intrauterine device and 23.8% for copper intrauterine device (P = .33). Black race, primiparity, and age were positively associated with discontinuation; education was not. The hazard ratio for discontinuation of levonorgestrel intrauterine device compared with copper intrauterine device >4 years was 0.71 (95% confidence interval, 0.55–0.93) and >5 years was 0.82 (95% confidence interval, 0.64–1.05) after adjusting for race, age, parity, and education. Copper intrauterine device users were more likely to experience expulsion (10.2% copper

Normal uniform mixture differential gene expression detection for cDNA microarrays

PubMed Central

Dean, Nema; Raftery, Adrian E

2005-01-01

Background One of the primary tasks in analysing gene expression data is finding genes that are differentially expressed in different samples. Multiple testing issues due to the thousands of tests run make some of the more popular methods for doing this problematic. Results We propose a simple method, Normal Uniform Differential Gene Expression (NUDGE) detection for finding differentially expressed genes in cDNA microarrays. The method uses a simple univariate normal-uniform mixture model, in combination with new normalization methods for spread as well as mean that extend the lowess normalization of Dudoit, Yang, Callow and Speed (2002) [1]. It takes account of multiple testing, and gives probabilities of differential expression as part of its output. It can be applied to either single-slide or replicated experiments, and it is very fast. Three datasets are analyzed using NUDGE, and the results are compared to those given by other popular methods: unadjusted and Bonferroni-adjusted t tests, Significance Analysis of Microarrays (SAM), and Empirical Bayes for microarrays (EBarrays) with both Gamma-Gamma and Lognormal-Normal models. Conclusion The method gives a high probability of differential expression to genes known/suspected a priori to be differentially expressed and a low probability to the others. In terms of known false positives and false negatives, the method outperforms all multiple-replicate methods except for the Gamma-Gamma EBarrays method to which it offers comparable results with the added advantages of greater simplicity, speed, fewer assumptions and applicability to the single replicate case. An R package called nudge to implement the methods in this paper will be made available soon at . PMID:16011807

Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction

PubMed Central

Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.

2012-01-01

The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

PubMed

Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

2017-03-01

Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1

How to normalize metatranscriptomic count data for differential expression analysis.

PubMed

Klingenberg, Heiner; Meinicke, Peter

2017-01-01

Differential expression analysis on the basis of RNA-Seq count data has become a standard tool in transcriptomics. Several studies have shown that prior normalization of the data is crucial for a reliable detection of transcriptional differences. Until now it has not been clear whether and how the transcriptomic approach can be used for differential expression analysis in metatranscriptomics. We propose a model for differential expression in metatranscriptomics that explicitly accounts for variations in the taxonomic composition of transcripts across different samples. As a main consequence the correct normalization of metatranscriptomic count data under this model requires the taxonomic separation of the data into organism-specific bins. Then the taxon-specific scaling of organism profiles yields a valid normalization and allows us to recombine the scaled profiles into a metatranscriptomic count matrix. This matrix can then be analyzed with statistical tools for transcriptomic count data. For taxon-specific scaling and recombination of scaled counts we provide a simple R script. When applying transcriptomic tools for differential expression analysis directly to metatranscriptomic data with an organism-independent (global) scaling of counts the resulting differences may be difficult to interpret. The differences may correspond to changing functional profiles of the contributing organisms but may also result from a variation of taxonomic abundances. Taxon-specific scaling eliminates this variation and therefore the resulting differences actually reflect a different behavior of organisms under changing conditions. In simulation studies we show that the divergence between results from global and taxon-specific scaling can be drastic. In particular, the variation of organism abundances can imply a considerable increase of significant differences with global scaling. Also, on real metatranscriptomic data, the predictions from taxon-specific and global scaling can differ

Intrauterine Growth Restriction and the Fetal Programming of the Hedonic Response to Sweet Taste in Newborn Infants

PubMed Central

Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C.; Silveira, Patrícia Pelufo

2012-01-01

Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals. PMID:22851979

Intrauterine growth restriction and the fetal programming of the hedonic response to sweet taste in newborn infants.

PubMed

Ayres, Caroline; Agranonik, Marilyn; Portella, André Krumel; Filion, Françoise; Johnston, Celeste C; Silveira, Patrícia Pelufo

2012-01-01

Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.

Myeloperoxidase in the plasma and placenta of normal pregnant women and women with pregnancies complicated by preeclampsia and intrauterine growth restriction.

PubMed

Hung, T-H; Chen, S-F; Lo, L-M; Li, M-J; Yeh, Y-L; Hsieh, T-T

2012-04-01

Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intrauterine growth restriction - part 2.

PubMed

Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2016-12-01

Small for gestational age (SGA) infants have been classically defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age, whereas intrauterine growth restriction (IUGR) has been defined as a rate of foetal growth that is less than normal for the population and for the growth potential of a specific infant. SGA infants have more frequent problems such as perinatal asphyxia, hypothermia, hypoglycaemia, polycythaemia and many more when compared with their appropriate for gestational age counterpart. They too have growth retardation and various major and subtle neurodevelopmental handicaps, with higher rates of perinatal and neonatal mortality. With the advent of newer technologies, even though the perinatal diagnosis of these SGA/IUGR foetuses has increased, but still perinatal morbidity and mortality rates are higher than normal foetuses and infants. In this part, we have covered neonatal IUGR classification, postnatal diagnosis, short-term and long-term complications faced by these IUGR infants.

The hepatic transcriptome of young suckling and aging intrauterine growth restricted male rats

PubMed Central

Freije, William A.; Thamotharan, Shanthie; Lee, Regina; Shin, Bo-Chul; Devaskar, Sherin U.

2015-01-01

Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation. PMID:25371150

The hepatic transcriptome of young suckling and aging intrauterine growth restricted male rats.

PubMed

Freije, William A; Thamotharan, Shanthie; Lee, Regina; Shin, Bo-Chul; Devaskar, Sherin U

2015-04-01

Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation. © 2014 Wiley Periodicals, Inc.

Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

PubMed

Rodriguez-Guerineau, Luciana; Perez-Cruz, Miriam; Gomez Roig, María D; Cambra, Francisco J; Carretero, Juan; Prada, Fredy; Gómez, Olga; Crispi, Fátima; Bartrons, Joaquim

2018-02-01

Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

A suspicious reason for Raynaud's phenomenon: Intrauterine device.

PubMed

Diken, Adem I; Yalçınkaya, Adnan; Aksoy, Eray; Yılmaz, Seyhan; Çağlı, Kerim

2015-06-01

Primary Raynaud's phenomenon may be insistent in patients under medical therapy, and intrauterine devices may be an unnoticed reason in these patients. Fluctuations in female sex hormone status were reported to be associated with the emergence of primary Raynaud's phenomenon symptoms. The use of intrauterine devices was not reported to be associated with Raynaud's phenomenon previously. Intrauterine device may stimulate vascular hyperactivity regarding hormonal or unknown mechanisms that result in Raynaud's phenomenon. We present a postmenopausal patient who complained of primary Raynaud's phenomenon symptoms and had recovery after the removal of her copper intrauterine device. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Laser-induced differential normalized fluorescence method for cancer diagnosis

DOEpatents

Vo-Dinh, Tuan; Panjehpour, Masoud; Overholt, Bergein F.

1996-01-01

An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample.

Laser-induced differential normalized fluorescence method for cancer diagnosis

DOEpatents

Vo-Dinh, T.; Panjehpour, M.; Overholt, B.F.

1996-12-03

An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample. 5 figs.

Intrauterine temperature during intrapartum amnioinfusion: a prospective observational study.

PubMed

Tomlinson, T M; Schaecher, C; Sadovsky, Y; Gross, G

2012-07-01

To determine the influence of routine intrapartum amnioinfusion (AI) on intrauterine temperature. Prospective observational study. Maternity unit, Barnes Jewish Hospital, St Louis, MO, USA. Forty women with singleton gestations and an indication for intrapartum intrauterine pressure catheter placement. Using a temperature probe, we digitally recorded intrauterine temperature every 10 minutes during labour. Amnioinfusion was administered according to a standard protocol using saline equilibrated to the ambient temperature. Mean intrauterine temperature during labour. Participants were monitored for a mean of 280 minutes (range 20-820). A total of 164 intrauterine temperature readings in the AI cohort were compared with 797 control measurements. When compared with controls, we observed a lower intrauterine temperature in the AI cohort (36.4 versus 37.4°C, P<0.01). More measurements in the AI cohort were recorded in the presence of intrapartum fever (40% versus 30%). A subgroup analysis of measurements recorded in afebrile parturients revealed an even greater effect of AI (1.5°C decrease, 37.3 versus 35.8°C, P<0.01). Routine intrapartum AI using saline equilibrated to a mean ambient temperature of 25.0°C reduces intrauterine temperature and may thereby affect fetal core temperature. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Levonorgestrel Intrauterine System

MedlinePlus

... Levonorgestrel may also prevent ovulation (release of an egg from the ovaries) in some women. Levonorgestrel intrauterine ... problem with your fallopian tubes (tubes that transport eggs that have been released by the ovaries to ...

Expression of myeloid differentiation antigens on normal and malignant myeloid cells.

PubMed Central

Griffin, J D; Ritz, J; Nadler, L M; Schlossman, S F

1981-01-01

A series of monoclonal antibodies have been characterized that define four surface antigens (MY3, MY4, MY7, and MY8) of human myeloid cells. They were derived from a fusion of the NS-1 plasmacytoma cell line with splenocytes from a mouse immunized with human acute myelomonocytic leukemia cells. MY3 and MY4 are expressed by normal monocytes and by greater than 90% of patients with acute monocytic leukemia or acute myelomonocytic leukemia, but are detected much less often on other types of myeloid leukemia. MY7 is expressed by granulocytes, monocytes, and 5% of normal bone marrow cells. 79% of all acute myeloblastic leukemia (AML) patients tested (72 patients) express MY7 without preferential expression by any AML subtype. MY8 is expressed by normal monocytes, granulocytes, all peroxidase-positive bone marrow cells, and 50% of AML patients. MY3, MY4, and MY8 define myeloid differentiation antigens in that they are not detected on myeloid precursor cells and appear at discrete stages of differentiation. These antigens are not expressed by lymphocytes, erythrocytes, platelets, or lymphoid malignancies. The monoclonal antisera defining these antigens have been used to study differentiation of normal myeloid cells and malignant cell lines. Images PMID:6945311

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue.

PubMed

Zhang, Jing; Fan, Yimeng; He, Min; Ma, Xuelei; Song, Yanlin; Liu, Ming; Xu, Jianguo

2017-05-30

Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.

Normalization and microbial differential abundance strategies depend upon data characteristics.

PubMed

Weiss, Sophie; Xu, Zhenjiang Zech; Peddada, Shyamal; Amir, Amnon; Bittinger, Kyle; Gonzalez, Antonio; Lozupone, Catherine; Zaneveld, Jesse R; Vázquez-Baeza, Yoshiki; Birmingham, Amanda; Hyde, Embriette R; Knight, Rob

2017-03-03

Data from 16S ribosomal RNA (rRNA) amplicon sequencing present challenges to ecological and statistical interpretation. In particular, library sizes often vary over several ranges of magnitude, and the data contains many zeros. Although we are typically interested in comparing relative abundance of taxa in the ecosystem of two or more groups, we can only measure the taxon relative abundance in specimens obtained from the ecosystems. Because the comparison of taxon relative abundance in the specimen is not equivalent to the comparison of taxon relative abundance in the ecosystems, this presents a special challenge. Second, because the relative abundance of taxa in the specimen (as well as in the ecosystem) sum to 1, these are compositional data. Because the compositional data are constrained by the simplex (sum to 1) and are not unconstrained in the Euclidean space, many standard methods of analysis are not applicable. Here, we evaluate how these challenges impact the performance of existing normalization methods and differential abundance analyses. Effects on normalization: Most normalization methods enable successful clustering of samples according to biological origin when the groups differ substantially in their overall microbial composition. Rarefying more clearly clusters samples according to biological origin than other normalization techniques do for ordination metrics based on presence or absence. Alternate normalization measures are potentially vulnerable to artifacts due to library size. Effects on differential abundance testing: We build on a previous work to evaluate seven proposed statistical methods using rarefied as well as raw data. Our simulation studies suggest that the false discovery rates of many differential abundance-testing methods are not increased by rarefying itself, although of course rarefying results in a loss of sensitivity due to elimination of a portion of available data. For groups with large (~10×) differences in the average

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

Intrauterine growth restriction affects the preterm infant's hippocampus.

PubMed

Lodygensky, Gregory A; Seghier, Mohammed L; Warfield, Simon K; Tolsa, Cristina Borradori; Sizonenko, Stephane; Lazeyras, François; Hüppi, Petra S

2008-04-01

The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.

Maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of human chorionic gonadotropin: a case report.

PubMed

Bakas, P; Tzouma, C; Creatsa, M; Boutas, I; Hassiakos, D

2016-01-01

To report a rare case of maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of hCG. A 36-year-old woman after successful intrauterine insemination and triplet pregnancy, developed hyperthyroidism with resistance to medical treatment. All signs of hyperthyroidism resolved and the results of thyroid function tests returned to normal without any medication after embryo meiosis. De novo maternal hyperthyroidism may develop during pregnancy as a result of pathological stimulation of the thyroid gland from the high levels of hCG hormone that can be seen in multiple pregnancies. The risk of hyperthyroidism is related to the number of fetuses. Reversibility of symptomatology can be seen after fetal reduction of multiple pregnancies.

Intrauterine fetal death and risk of shoulder dystocia at delivery.

PubMed

Larsen, Sandra; Dobbin, Joanna; McCallion, Oliver; Eskild, Anne

2016-12-01

Vaginal delivery is recommended after intrauterine fetal death. However, little is known about the risk of shoulder dystocia in these deliveries. We studied whether intrauterine fetal death increases the risk of shoulder dystocia at delivery. In this population-based register study using the Medical Birth Registry of Norway, we included all singleton pregnancies with vaginal delivery of offspring in cephalic presentation in Norway during the period 1967-2012 (n = 2 266 118). Risk of shoulder dystocia was estimated as absolute risk (%) and odds ratio with 95% confidence interval. Adjustment was made for offspring birthweight (in grams). We performed sub-analyses within categories of birthweight (<4000 and ≥4000 g) and in pregnancies with maternal diabetes. Shoulder dystocia occurred in 1.1% of pregnancies with intrauterine fetal death and in 0.8% of pregnancies without intrauterine fetal death (p < 0.0001) (crude odds ratio 1.5, 95% confidence interval 1.2-4.9). After adjustment for birthweight, the odds ratio was 5.9 (95% confidence interval 4.7-7.4). In pregnancies with birthweight ≥4000 g, shoulder dystocia occurred in 14.6% of pregnancies with intrauterine fetal death and in 2.8% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 5.9, 95% confidence interval 4.5-7.9). In pregnancies with birthweight ≥4000 g and concurrent maternal diabetes, shoulder dystocia occurred in 57.1% of pregnancies with intrauterine fetal death and 9.6% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 12.6, 95% confidence interval 5.9-26.9). Intrauterine fetal death increased the risk of shoulder dystocia at delivery, and the absolute risk of shoulder dystocia was particularly high if offspring birthweight was high and the mother had diabetes. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial.

PubMed

Navali, N; Gassemzadeh, A; Farzadi, L; Abdollahi, S; Nouri, M; Hamdi, K; Mallah, F; Jalilvand, F

2016-11-01

Does the intrauterine administration of hCG immediately after oocyte retrieval in antagonist cycles with ICSI and fresh embryo transfer (ET) influence the implantation rate or chemical and clinical pregnancy rates? The intrauterine administration of hCG after oocyte retrieval increases the implantation rate and chemical and clinical pregnancy rates. Over half of IVF/ICSI cycles fail due to implantation failure. Intrauterine administration of hCG, a few minutes before ET, increased the implantation and pregnancy rates in most but not in all studies. The effect of intrauterine administration of hCG, after oocyte retrieval, has not yet been studied. The study was a parallel, triple-blind randomized clinical trial (RCT) performed from September 2015 to February 2016, in a university hospital. We recruited women undergoing antagonist ovarian stimulation, ICSI and ET. For an effect size of 0.2, power of 80% at a significance level of 0.05, we needed 150 participants. Accounting for a 7% dropout rate, a total of 160 women was considered appropriate. A computer-generated randomization list with a block size of 4, with 1:1 allocation was used. The treatment allocation was placed in a sealed, opaque, envelope and picked up consecutively. Immediately after oocyte retrieval, patients in the intervention and control groups were treated with intrauterine injection of hCG and saline, respectively. Participants underwent ET on Day 3. A beta-hCG test was done at 2 weeks. If positive, three transvaginal-ultrasonographies (TVSs) were done at 3, 4 and 10 weeks after ET. The participants were called up thereafter and questioned about the continuity of their pregnancy. Of 1990 women attending the infertility clinic of our university hospital, 508 were IVF/ICSI candidates during the study period, and 245 of the patients on an antagonist cycle met the criteria to be invited into our trial. Inclusion criteria were normal ovarian reserve, age ≤41, undergoing ICSI, and fresh ET and normal

Effects of intrauterine contraception on the vaginal microbiota.

PubMed

Bassis, Christine M; Allsworth, Jenifer E; Wahl, Heather N; Sack, Daniel E; Young, Vincent B; Bell, Jason D

2017-09-01

There have been conflicting reports of altered vaginal microbiota and infection susceptibility associated with contraception use. The objectives of this study were to determine if intrauterine contraception altered the vaginal microbiota and to compare the effects of a copper intrauterine device (Cu-IUD) and a levonorgestrel intrauterine system (LNG-IUS) on the vaginal microbiota. DNA was isolated from the vaginal swab samples of 76 women using Cu-IUD (n=36) or LNG-IUS (n=40) collected prior to insertion of intrauterine contraception (baseline) and at 6 months. A third swab from approximately 12 months following insertion was available for 69 (Cu-IUD, n=33; LNG-IUS, n=36) of these women. The V4 region of the bacterial 16S rRNA-encoding gene was amplified from the vaginal swab DNA and sequenced. The 16S rRNA gene sequences were processed and analyzed using the software package mothur to compare the structure and dynamics of the vaginal bacterial communities. The vaginal microbiota from individuals in this study clustered into 3 major vaginal bacterial community types: one dominated by Lactobacillus iners, one dominated by Lactobacillus crispatus and one community type that was not dominated by a single Lactobacillus species. Changes in the vaginal bacterial community composition were not associated with the use of Cu-IUD or LNG-IUS. Additionally, we did not observe a clear difference in vaginal microbiota stability with Cu-IUD versus LNG-IUS use. Although the vaginal microbiota can be highly dynamic, alterations in the community associated with the use of intrauterine contraception (Cu-IUD or LNG-IUS) were not detected over 12 months. We found no evidence that intrauterine contraception (Cu-IUD or LNG-IUS) altered the vaginal microbiota composition. Therefore, the use of intrauterine contraception is unlikely to shift the composition of the vaginal microbiota such that infection susceptibility is altered. Copyright © 2017 Elsevier Inc. All rights reserved.

An Effective Technique for Enhancing an Intrauterine Catheter Fetal Electrocardiogram

NASA Astrophysics Data System (ADS)

Horner, Steven L.; Holls, William M.

2003-12-01

Physician can obtain fetal heart rate, electrophysiological information, and uterine contraction activity for determining fetal status from an intrauterine catheters electrocardiogram with the maternal electrocardiogram canceled. In addition, the intrauterine catheter would allow physicians to acquire fetal status with one non-invasive to the fetus biosensor as compared to invasive to the fetus scalp electrode and intrauterine pressure catheter used currently. A real-time maternal electrocardiogram cancellation technique of the intrauterine catheters electrocardiogram will be discussed along with an analysis for the methods effectiveness with synthesized and clinical data. The positive results from an original detailed subjective and objective analysis of synthesized and clinical data clearly indicate that the maternal electrocardiogram cancellation method was found to be effective. The resulting intrauterine catheters electrocardiogram from effectively canceling the maternal electrocardiogram could be used for determining fetal heart rate, fetal electrocardiogram electrophysiological information, and uterine contraction activity.

Creatinine concentrations of accumulated intrauterine fluid to confirm the clinical diagnosis of urometra in mares.

PubMed

Schnobrich, M R; Gordon, D L; Scoggin, C F; Bradecamp, E A; Canisso, I F

2017-03-25

Urine pooling, as a persistent condition, is a cause of infertility in mares due to endometrial inflammation and sperm toxicity. Identification of urometra can be challenging in mares presenting with the condition intermittently, or when urine flows into the uterus but is undetectable in the vagina. Currently, there are no reported objective methods to confirm the clinical diagnosis of urine contamination in intrauterine-fluid accumulations. Since creatinine is present in high concentrations in urine and does not diffuse across cell membranes, creatinine concentration should be increased in mares with urometra, but negligible in normal and mares with intrauterine fluid accumulation (non-urometra cases). To test this hypothesis, creatinine concentrations of intrauterine fluid were measured in mares with a clinical diagnosis of urine accumulation (n=9) or intrauterine fluid containing no urine (n=10). Results showed that creatinine concentrations (mg/dl) were significantly higher in mares that had a clinical diagnosis of urometra (42.8±12.6, range 4.1-109.2) compared with those that did not (0.38±0.1, range 0-0.9). Also, two mares after urethral extension surgery demonstrated a remarkable reduction in creatinine concentrations. This study highlights an undocumented approach to confirm a clinical diagnosis of urometra in mares; the authors anticipate that testing for creatinine in the uterine fluid of mares may become a standard tool for identifying urometra in mares and confirming the success of urogenital surgeries. British Veterinary Association.

21 CFR 529.50 - Amikacin sulfate intrauterine solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amikacin sulfate intrauterine solution. 529.50... Amikacin sulfate intrauterine solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 250 milligrams of amikacin (as the sulfate). (b) Sponsor. See No. 000856 and 059130 in § 510.600(c...

Immediate metabolic consequences of intrauterine growth restriction and low birthweight.

PubMed

Bhatia, Jatinder; Gates, Amy

2013-01-01

Optimal fetal growth resulting in a 'normally grown' term infant is of paramount importance for assuring a healthy start for postnatal growth and development. Fetal, infant and childhood growth restriction is an important clinical problem for obstetricians, neonatologists, pediatricians and globally, for public health. Worldwide, an estimated 20 million infants are born with low birthweight and a substantial proportion are small for gestational age. Many advances have been made in defining growth restriction by prenatal techniques, thus allowing the recognition of intrauterine growth restriction. Distinguishing infants who are small but have appropriate growth potential from those with growth restriction is important in order to apply obstetric surveillance, anticipate neonatal problems and plan for postneonatal guidance. It is clear that the fetus in growth-restricted pregnancies has limited supply of nutrients and oxygen. The resultant changes, if involving the placenta as well, can lead to circulatory and metabolic changes affecting both short- and long-term survival and development. In this paper, the causes and immediate consequence of being born with low birthweight, intrauterine growth restriction or small for gestational age will be discussed. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

Differential Transcriptional Response in Macrophages Infected with Cell Wall Deficient versus Normal Mycobacterium Tuberculosis

PubMed Central

Fu, Yu-Rong; Gao, Kun-Shan; Ji, Rui; Yi, Zheng-Jun

2015-01-01

Host-pathogen interactions determine the outcome following infection by mycobacterium tuberculosis (Mtb). Under adverse circumstances, normal Mtb can form cell-wall deficient (CWD) variants within macrophages, which have been considered an adaptive strategy for facilitating bacterial survival inside macrophages. However, the molecular mechanism by which infection of macrophages with different phenotypic Mtb elicits distinct responses of macrophages is not fully understood. To explore the molecular events triggered upon Mtb infection of macrophages, differential transcriptional responses of RAW264.7 cells infected with two forms of Mtb, CWD-Mtb and normal Mtb, were studied by microarray analysis. Some of the differentially regulated genes were confirmed by RT-qPCR in both RAW264.7 cells and primary macrophages. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was used to analyze functions of differentially expressed genes. Distinct gene expression patterns were observed between CWD-Mtb and normal Mtb group. Mapt was up-regulated, while NOS2 and IL-11 were down-regulated in CWD-Mtb infected RAW264.7 cells and primary macrophages compared with normal Mtb infected ones. Many deregulated genes were found to be related to macrophages activation, immune response, phagosome maturation, autophagy and lipid metabolism. KEGG analysis showed that the differentially expressed genes were mainly involved in MAPK signaling pathway, nitrogen metabolism, cytokine-cytokine receptor interaction and focal adhesion. Taken together, the present study showed that differential macrophage responses were induced by intracellular CWD-Mtb an normal Mtb infection, which suggested that interactions between macrophages and different phenotypic Mtb are very complex. The results provide evidence for further understanding of pathogenesis of CWD-Mtb and may help in improving strategies to eliminate intracellular CWD-Mtb. PMID:25552926

Best practices to minimize risk of infection with intrauterine device insertion.

PubMed

Caddy, Sheila; Yudin, Mark H; Hakim, Julie; Money, Deborah M

2014-03-01

Intrauterine devices provide an extremely effective, long-term form of contraception that has the benefit of being reversible. Historically, the use of certain intrauterine devices was associated with increased risk of pelvic inflammatory disease. More recent evidence suggests that newer devices do not carry the same threat; however, certain risk factors can increase the possibility of infection. To review the risk of infection with the insertion of intrauterine devices and recommend strategies to prevent infection. The outcomes considered were the risk of pelvic inflammatory disease, the impact of screening for bacterial vaginosis and sexually transmitted infections including chlamydia and gonorrhea; and the role of prophylactic antibiotics. Published literature was retrieved through searches of PubMed, Embase, and The Cochrane Library on July 21, 2011, using appropriate controlled vocabulary (e.g., intrauterine devices, pelvic inflammatory disease) and key words (e.g., adnexitis, endometritis, IUD). An etiological filter was applied in PubMed. The search was limited to the years 2000 forward. There were no language restrictions. Grey (unpublished) literature was identified through searching the web sites of national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table). Recommendations 1. All women requesting an intrauterine device should be counselled about the small increased risk of pelvic inflammatory disease in the first 20 days after insertion. (II-2A) 2. All women requesting an intrauterine device should be screened by both history and physical examination for their risk of sexually transmitted infection. Women at increased risk should be tested prior to or at the time of insertion; however, it is not necessary to delay insertion until results are returned. (II-2B) 3. Not enough current evidence is available

Recurrent chronic histiocytic intervillositis with intrauterine growth restriction, osteopenia, and fractures.

PubMed

Crawford, April; Moore, Lynette; Bennett, Gregory; Savarirayan, Ravi; Manton, Nicholas; Khong, Yee; Barnett, Christopher P; Haan, Eric

2016-11-01

Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Infection risk and intrauterine devices.

PubMed

Martínez, Francisca; López-Arregui, Eduardo

2009-01-01

For most women, intrauterine contraceptive devices (IUCD) are a safe option. Upper genital tract infections (pelvic inflammatory disease, PID) occur when pathogenic microorganisms ascend from the cervix and invade the endometrium and the fallopian tubes, causing an inflammatory reaction. Evidence-based recommendations regarding intrauterine contraception and risk of infection were presented at the Congress of the European Society of Contraception, in Prague, 2008: A clinical history (including sexual history) should be taken as part of the routine assessment for intrauterine contraception to identify women at high risk of sexually transmitted infections (STI); if appropriate a test should be offered; if symptoms or signs are present, appropriate diagnostic tests should be done, results awaited, necessary treatment completed, and IUCD insertion postponed until resolution. Prophylactic antibiotics are not recommended (evidence level II-3). STI screening is not routinely recommended. PID among IUCD users is most strongly related to the insertion process and to the background risk of STI (evidence level II-2). Conditions which represent an unacceptable health risk if an IUCD is inserted (WHO Medical Eligibility Criteria, MEC, Categories 3-4) are current PID, current purulent cervicitis, chlamydial or gonorrheal infection. For continuation as well as initiation, WHO MEC categories 3-4 are allotted to women with known pelvic tuberculosis, puerperal sepsis and septic abortion.

A new familial intrauterine growth retardation syndrome the "3-M syndrome".

PubMed

Spranger, J; Opitz, J M; Nourmand, A

1976-09-01

Two pairs of siblings are described with proportionate dwarfism due to skeletal hypoplasia of prenatal onset. The head size was normal for age and disproportionately large for height. The patients had a characteristic face different from that seen in the Silver-Russell syndrome. The family data are in accordance with autosomal recessive inheritance. In spite of some similarities, the bulk of clinical and genetic evidence suggests that the described intrauterine growth retardation syndrome is different from the Silver-Russell syndrome and presents an apparently "new" entity which has been designated 3-M syndrome.

Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

PubMed

Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

2015-08-01

To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

[Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction].

PubMed

Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László

2017-04-01

Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 000859...

Comparison of normalization methods for differential gene expression analysis in RNA-Seq experiments

PubMed Central

Maza, Elie; Frasse, Pierre; Senin, Pavel; Bouzayen, Mondher; Zouine, Mohamed

2013-01-01

In recent years, RNA-Seq technologies became a powerful tool for transcriptome studies. However, computational methods dedicated to the analysis of high-throughput sequencing data are yet to be standardized. In particular, it is known that the choice of a normalization procedure leads to a great variability in results of differential gene expression analysis. The present study compares the most widespread normalization procedures and proposes a novel one aiming at removing an inherent bias of studied transcriptomes related to their relative size. Comparisons of the normalization procedures are performed on real and simulated data sets. Real RNA-Seq data sets analyses, performed with all the different normalization methods, show that only 50% of significantly differentially expressed genes are common. This result highlights the influence of the normalization step on the differential expression analysis. Real and simulated data sets analyses give similar results showing 3 different groups of procedures having the same behavior. The group including the novel method named “Median Ratio Normalization” (MRN) gives the lower number of false discoveries. Within this group the MRN method is less sensitive to the modification of parameters related to the relative size of transcriptomes such as the number of down- and upregulated genes and the gene expression levels. The newly proposed MRN method efficiently deals with intrinsic bias resulting from relative size of studied transcriptomes. Validation with real and simulated data sets confirmed that MRN is more consistent and robust than existing methods. PMID:26442135

The case for intrauterine stem cell transplantation.

PubMed

Mattar, Citra N; Biswas, Arijit; Choolani, Mahesh; Chan, Jerry K Y

2012-10-01

The clinical burden imposed by the collective group of monogenic disorders demands novel therapies that are effective at achieving phenotypic cure early in the disease process before the development of permanent organ damage. This is important for lethal diseases and also for non-perinatally lethal conditions that are characterised by severe disability with little prospect of postnatal cure. Where postnatal treatments are limited to palliative options, intrauterine stem-cell therapies may offer the potential to arrest pathogenesis in the early undamaged fetus. Intrauterine stem-cell transplantation has been attempted for a variety of diseases, but has only been successful in immune deficiency states in the presence of a competitive advantage for donor cells. This disappointing clinical record requires preclinical investigations into strategies that improve donor cell engraftment, including optimising the donor cell source and manipulating the microenvironment to facilitate homing. This chapter aims to outline the current challenges of intrauterine stem-cell therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

ACR Appropriateness Criteria® growth disturbances - risk of intrauterine growth restriction.

PubMed

Zelop, Carolyn M; Javitt, Marcia C; Glanc, Phyllis; Dubinsky, Theodore; Harisinghani, Mukesh G; Harris, Robert D; Khati, Nadia J; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Wong-You-Cheong, Jade J

2013-09-01

Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Comparison of copper intrauterine device with levonorgestrel-bearing intrauterine system for post-abortion contraception.

PubMed

Bilgehan, Fatma; Dilbaz, Berna; Karadag, Burak; Deveci, Canan Dura

2015-09-01

The aim of this study was to compare the safety, bleeding pattern, effects, side-effects, complications and 6-month continuity rates of levonorgestrel-bearing intrauterine system (LNG-IUS) with conventional copper intrauterine device (Cu-IUD) inserted immediately after voluntary termination of pregnancy up to 10 weeks of gestation. One hundred women who underwent voluntary pregnancy termination and preferred IUD insertion as a contraceptive method after counseling were enrolled. The patients were randomly allocated to Cu-IUD or LNG-IUS and followed up at 10 days, and at 1, 3 and 6 months. The expulsion rates, continuation rates, side-effects, and bleeding patterns were compared. Fifty women in the Cu-IUD group and 44 women in the LNG-IUS group were followed up. The continuity and expulsion rate for Cu-IUD and LNG-IUS at the end of 6 months was 74%, 12%, and 75%, 11.3%, respectively. In LNG-IUS users, the incidence of amenorrhea and the number of spotting days were higher and hemoglobin increased throughout the follow-up period. The side-effects related to both methods were not different from interval insertions. Immediate post-abortion intrauterine contraception with Cu-IUD or LNG-IUS is a safe, reliable method. The incidence of side-effects is similar, and there is only a slightly higher rate of expulsion but an acceptable rate of method continuation. © 2015 Japan Society of Obstetrics and Gynecology.

Normal neutrophil differentiation and secondary granule gene expression in the EML and MPRO cell lines.

PubMed

Lawson, N D; Krause, D S; Berliner, N

1998-11-01

The EML and MPRO cell lines express a dominant negative retinoic acid receptor alpha that causes a block at specific stages of myelopoiesis. The EML cell line is multipotent and gives rise to erythroid, lymphoid, and myeloid lineages depending on the presence of appropriate cytokines. The MPRO cell line is promyelocytic and undergoes neutrophilic differentiation when induced with all-trans retinoic acid in the presence of granulocyte/macrophage colony-stimulating factor. Previous studies have shown that both of these cell lines undergo morphological differentiation into neutrophils. In this study, we show that unlike other models of neutrophil differentiation such as NB4 and HL60, both EML and MPRO cell lines undergo complete, normal granulocytic differentiation programs. Similar to HL60, MPRO and EML induce expression of CD11b/CD18 and also exhibit downregulation of CD34 on differentiation. In contrast to HL60 and NB4, EML and MPRO cell lines coordinately upregulate secondary granule transcripts for lactoferrin and neutrophil gelatinase. Furthermore, we have confirmed previous observations that serum can induce a low level of differentiation in MPRO cells and that it is possible to grow these cells in serum-free medium, thereby eliminating this effect. Based on these studies, it appears that these lines can serve as a model for normal retinoic acid-induced neutrophil differentiation and provide insight into the role of the retinoic acid-responsive pathway in normal and leukemic myelopoiesis.

Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

NASA Technical Reports Server (NTRS)

Ronca, A. E.; Baer, L. A.; Wade, C. E.

2003-01-01

Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.

PubMed

Nelson, Anita; Apter, Dan; Hauck, Brian; Schmelter, Thomas; Rybowski, Sarah; Rosen, Kimberly; Gemzell-Danielsson, Kristina

2013-12-01

To evaluate the efficacy and safety of two low-dose levonorgestrel intrauterine contraceptive systems. Nulliparous and parous women aged 18-35 years with regular menstrual cycles (21-35 days) requesting contraception were randomized to 3 years of treatment with one of two levonorgestrel intrauterine contraceptive systems: 13.5 mg total content or 19.5 mg total content. The primary outcome was the pregnancy rate, calculated as the Pearl Index. Overall, 1,432 and 1,452 women in the 13.5 mg intrauterine contraceptive system and 19.5 mg intrauterine contraceptive system groups, respectively, had a placement attempted and were included in the full analysis set to evaluate efficacy and safety. Mean (standard deviation) age was 27.1 (4.8) years; 39.2% were nulliparous. Over the 3-year study period, 0.33 pregnancies per 100 women-years (95% confidence interval [CI] 0.16-0.60) were observed with the 13.5 mg intrauterine contraceptive system compared with 0.31 per 100 women-years (95% CI 0.15-0.57) with the 19.5 mg intrauterine contraceptive system. Kaplan-Meier estimates for that period were 0.009 and 0.010, respectively. At least partial expulsions occurred in 4.56% and 3.58% and discontinuation rates resulting from a reported adverse event occurred in 21.9% and 19.1%, respectively. Ten of the 20 pregnancies were ectopic. Serious adverse events included six cases of pelvic inflammatory disease and one partial uterine perforation. Both lower-dose levonorgestrel intrauterine contraceptive systems were highly effective for 3 years of use and generally well tolerated. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00528112. : I.

Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland.

PubMed

Soini, Tuuli; Hurskainen, Ritva; Grénman, Seija; Mäenpää, Johanna; Paavonen, Jorma; Pukkala, Eero

2014-08-01

To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma. All Finnish women aged 30-49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994-2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population. A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35-0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05-0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45-0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28-0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49-0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13-1.25; 1,542 observed compared with 1,292 expected cases). The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected

New operational technology of intrauterine ventilation the fetus lungs by breathing gas

NASA Astrophysics Data System (ADS)

Urakov, A. L.; Nikityuk, D. B.; Urakova, N. A.; Kasankin, A. A.; Chernova, L. V.; Dementiev, V. B.

2015-11-01

New operational technology for elimination intrauterine hypoxia and asphyxia of the fetus using endoscopic artificial ventilation lungs by respiratory gas was developed. For intrauterine ventilation of fetal lung it is proposed to enter into the uterus a special breathing mask and wear it on the head of the fetus using the original endoscopic technology. The breathing mask, developed by us is connected with external breathing apparatus with a hose. The device is called "intrauterine aqualung". Intrauterine aqualung includes a ventilator and breathing circuit with a special fold-out breathing mask that is put on inside the uterus on the head of fetus like a mesh hat. Controlled by ultrasound the technology of the introduction of the mask inside of the uterus through the natural opening in the cervix and technology of putting on the respiratory mask on the head of the fetus with its head previa were developed. The technology intrauterine ventilation of the fetus lungs by respiratory gas was developed.

Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2013-01-01

The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction. The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays. A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia. These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

Differential Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones

NASA Astrophysics Data System (ADS)

Nakajima, Hideko Heidi; Dong, Wei; Olson, Elizabeth S.; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.

2009-02-01

We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. Micro-scale fiberoptic pressure sensors enabled the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. Results showed that: pressure of scala vestibuli was much greater than scala tympani except at low and high frequencies where scala tympani pressure affects the input to the cochlea; the differential pressure proved to be an excellent measure of normal ossicular transduction of sound (shown to decrease 30-50 dB with ossicular disarticulation, whereas the individual scala pressures were significantly affected by non-ossicular conduction of sound at high frequencies); the middle-ear gain and differential pressure were generally bandpass in frequency dependence; and the middle-ear delay in the human was over twice that of the gerbil. Concurrent stapes velocity measurements allowed determination of the differential impedance across the partition and round-window impedance. The differential impedance was generally resistive, while the round-window impedance was consistent with a compliance in conjunction with distributed inertia and damping. Our techniques can be used to study inner-ear conductive pathologies (e.g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e.g., round-window stimulation) - situations that cannot be completely quantified by measurements of stapes velocity or scala-vestibuli pressure by themselves.

Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

PubMed

Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

2014-01-01

Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

NASA Astrophysics Data System (ADS)

Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

2016-07-01

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

BCG vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity.

PubMed Central

Mussi-Pinhata, M. M.; Goncalves, A. L.; Foss, N. T.

1993-01-01

To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination. PMID:8440036

Predictive factors for intrauterine growth restriction

PubMed Central

Albu, AR; Anca, AF; Horhoianu, VV; Horhoianu, IA

2014-01-01

Abstract Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. Abbreviations: SGA = small for gestational age; IUGR = intrauterine growth restriction; FGR = fetal growth restriction; IUFD = intrauterine fetal demise; HIV = human immunodeficiency virus; PAPP-A = pregnancy associated plasmatic protein A; β-hCG = beta human chorionic gonadotropin; MoM = multiple of median; ADAM-12 = A-disintegrin and metalloprotease 12; PP-13 = placental protein 13; VEGF = vascular endothelial growth factor; PlGF = placental growth factor; sFlt-1 = soluble fms-like tyrosine kinase-1; UAD = uterine arteries Doppler ultrasound; RI = resistence index; PI = pulsatility index; VOCAL = Virtual Organ Computer–Aided Analysis software; VI = vascularization index; FI = flow index; VFI = vascularization flow index; PQ = placental quotient PMID:25408721

Super-delta: a new differential gene expression analysis procedure with robust data normalization.

PubMed

Liu, Yuhang; Zhang, Jinfeng; Qiu, Xing

2017-12-21

Normalization is an important data preparation step in gene expression analyses, designed to remove various systematic noise. Sample variance is greatly reduced after normalization, hence the power of subsequent statistical analyses is likely to increase. On the other hand, variance reduction is made possible by borrowing information across all genes, including differentially expressed genes (DEGs) and outliers, which will inevitably introduce some bias. This bias typically inflates type I error; and can reduce statistical power in certain situations. In this study we propose a new differential expression analysis pipeline, dubbed as super-delta, that consists of a multivariate extension of the global normalization and a modified t-test. A robust procedure is designed to minimize the bias introduced by DEGs in the normalization step. The modified t-test is derived based on asymptotic theory for hypothesis testing that suitably pairs with the proposed robust normalization. We first compared super-delta with four commonly used normalization methods: global, median-IQR, quantile, and cyclic loess normalization in simulation studies. Super-delta was shown to have better statistical power with tighter control of type I error rate than its competitors. In many cases, the performance of super-delta is close to that of an oracle test in which datasets without technical noise were used. We then applied all methods to a collection of gene expression datasets on breast cancer patients who received neoadjuvant chemotherapy. While there is a substantial overlap of the DEGs identified by all of them, super-delta were able to identify comparatively more DEGs than its competitors. Downstream gene set enrichment analysis confirmed that all these methods selected largely consistent pathways. Detailed investigations on the relatively small differences showed that pathways identified by super-delta have better connections to breast cancer than other methods. As a new pipeline, super

Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction.

PubMed

Hu, Yue; Hu, Liang; Gong, Desheng; Lu, Hanlin; Xuan, Yue; Wang, Ru; Wu, De; Chen, Daiwen; Zhang, Keying; Gao, Fei; Che, Lianqiang

2018-02-01

Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates. The results revealed extensively regional DNA methylation changes between IUGR/NBW pairs from different gilts, affecting dozens of genes. Hiseq-based bisulfite sequencing PCR (Hiseq-BSP) was used for validations of 19 genes with epigenetic abnormality, confirming three genes (AIFM1, MTMR1, and TWIST2) in extra samples. Furthermore, integrated analysis of these 19 genes with proteome data indicated that there were three main genes (BCAP31, IRAK1, and AIFM1) interacting with important immunity- or metabolism-related proteins, which could explain the potential intestinal dysfunctions of IUGR piglets. We conclude that IUGR can lead to disparate DNA methylation in the intestine and these changes may affect several important biological processes such as cell apoptosis, cell differentiation, and immunity, which provides more clues linking IUGR and its long-term complications.

Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

PubMed Central

Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

2016-01-01

Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

Intrauterine adhesions as a risk factor for failed first-trimester pregnancy termination.

PubMed

Luk, Janelle; Allen, Rebecca H; Schantz-Dunn, Julianna; Goldberg, Alisa B

2007-10-01

Risk factors for failed first-trimester surgical abortion include endometrial distortion caused by leiomyomas, uterine anomalies and malposition and cervical stenosis. This report introduces intrauterine adhesions as an additional risk factor. A multiparous woman presented for pregnancy termination at 6 weeks' gestation. Three suction-curettage attempts failed to remove what appeared to be an intrauterine pregnancy. Rising beta-hCG levels and concern for an interstitial ectopic pregnancy prompted a diagnostic laparoscopy and exploratory laparotomy without the identification of an ectopic pregnancy. After methotrexate treatment failed, the patient underwent ultrasound-guided hysteroscopy and suction curettage using a cannula with a whistle-cut aperture for the successful removal of a pregnancy implanted behind intrauterine adhesions. Intrauterine adhesions are a cause of failed surgical abortion. Ultrasound-guided hysteroscopy may be required for diagnosis.

Molecular mechanisms of intrauterine growth restriction.

PubMed

Gurugubelli Krishna, Rao; Vishnu Bhat, B

2017-07-10

Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.

Review: Neuroinflammation in intrauterine growth restriction.

PubMed

Wixey, Julie A; Chand, Kirat K; Colditz, Paul B; Bjorkman, S Tracey

2017-06-01

Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study

ERIC Educational Resources Information Center

El Marroun, Hanan; Tiemeier, Henning; Steegers, Eric A. P.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; van den Brink, Wim; Huizink, Anja C.

2009-01-01

Objective: Cannabis is the most commonly consumed illicit drug among pregnant women. Intrauterine exposure to cannabis may result in risks for the developing fetus. The importance of intrauterine growth on subsequent psychological and behavioral child development has been demonstrated. This study examined the relation between maternal cannabis use…

Hysteroscopic sterilization of patient with intrauterine device Mirena®

PubMed Central

Depes, Daniella De Batista; Pereira, Ana Maria Gomes; Yatabe, Salete; Lopes, Reginaldo Guedes Coelho

2013-01-01

ABSTRACT Tubal sterilization is the definitive procedure most often used worldwide to control fecundity. Laparoscopic ligature is safe, but invasive and with possible surgical and anesthetic risks. The hysteroscopic approach enables tubal occlusion at outpatient's setting without the need of incisions or anesthesia. A microdevice (Essure®) is inserted directly into the tubes and its polyethelene fibers cause obstruction of tubes in about three months. During this period, it is recommended that patients continue the use of a temporary birth control method. Several women use the levonorgestrel-releasing intrauterine system, which is called in the market as Mirena®. This report evaluated the possibility of inserting Essure® without remove the intrauterine device; patient tolerance to the procedure was also assessed. The tubal device was successfully placed in the patient without the need to remove Mirena®. After three months the intrauterine device was removed with no intercurrent events. PMID:23579753

Pelvic infection: a comparison of the Dalkon shield and three other intrauterine devices.

PubMed Central

Snowden, R; Pearson, B

1984-01-01

A detailed analysis was undertaken of reports of possible pelvic infection in relation to the use of four commonly fitted intrauterine contraceptive devices during 1971 to 1978 in the United Kingdom. The four devices were the Dalkon shield, Lippes loops 3C and 2D, and the Gravigard (copper 7), and data used were those collected systematically through the UK intrauterine device research network. Prospective reports that the Dalkon shield was uniquely related to high levels of infection when compared with other intrauterine devices were not substantiated in this prospective study among 13 349 users. Though some factors such as social class and previous experience of abortion appeared to influence the rate of infection, the type of intrauterine device being worn did not appear to be a significant factor. Various methods of analysis were used including life table, regression, and discriminant analysis, using information relating to the type of intrauterine device worn, the characteristics of the user, the fitting centre, and the pattern of diagnosis and treatment of reported or suspected pelvic infection. The results of this study suggest that fears that the Dalkon shield may be associated with a higher incidence of pelvic infection than other intrauterine devices may have been unjustified. PMID:6426647

The levonorgestrel-releasing intrauterine system: Safety, efficacy, and patient acceptability

PubMed Central

Beatty, Megan N; Blumenthal, Paul D

2009-01-01

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy. Overall, the system is very well tolerated and patient satisfaction is quite high when proper education regarding possible side effects is provided. However, despite all of the obvious benefits of the LNG-IUS, utilization rates remain quite low in the developed countries, especially in the United States. This is thought to be largely secondary to the persistent negative impressions from the Dalkon Shield intrauterine experience in the 1970s. This history continues to negatively influence the opinions of both patients and health care providers with regards to intrauterine devices. Providers should resolve to educate themselves and their patients on the current indications and uses for this device, as it, and intrauterine contraception in general, remains a largely underutilized approach to a variety of women’s health issues. PMID:19707273

Clinical and Demographic Characteristics of Women with Intrauterine Adhesion in Abuja, Nigeria

PubMed Central

Efetie, Efena R.; Umezulike, Augustine C.; Okafor, Ugochukwu V.

2012-01-01

Objective. Infertility menstrual abnormalities continue to constitute a significant bulk of gynecological consultation in Africa. Both of these problems are sometimes traced to intrauterine adhesions which are preventable in the majority of cases. Study Design. A retrospective analysis of intrauterine adhesions at the National Hospital Abuja, Nigeria, was carried out, covering the period from 1st September 1999 to 1st September 2004. A total of 72 cases were analyzed. Statical analysis was done using X 2. Results. The incidence of intrauterine adhesions was 1.73% of new patients. Mean age ± SD was 29.97 ± 4.82 years. Patients who were Para 0 to 1 constituted 81.9% of the total. Intrauterine adhesions significantly (P < 0.02) occurred in nulliparae. The majority (68%) were educated only up to secondary level which was significant (P < 0.05). Menstrual abnormalities were present in 90.3%. The commonest predisposing factor identified was a history of dilatation and curettage or uterine evacuation. Conclusion. Intrauterine adhesions are associated with lower educational status and low parity. Increasing educational targets nationally, poverty alleviation, nationwide retraining in manual vacuum aspiration, and wider application of this technique are recommended. PMID:22190953

Intrauterine Insemination: Fundamentals Revisited.

PubMed

Allahbadia, Gautam N

2017-12-01

Intrauterine insemination (IUI) is an assisted conception technique that involves the deposition of a processed semen sample in the upper uterine cavity, overcoming natural barriers to sperm ascent in the female reproductive tract. It is a cost-effective, noninvasive first-line therapy for selected patients with functionally normal tubes, and infertility due to a cervical factor, anovulation, moderate male factor, unexplained factors, immunological factor, and ejaculatory disorders with clinical pregnancy rates per cycle ranging from 10 to 20%. It, however, has limited use in patients with endometriosis, severe male factor infertility, tubal factor infertility, and advanced maternal age ≥ 35 years. IUI may be performed with or without ovarian stimulation. Controlled ovarian stimulation, particularly with low-dose gonadotropins, with IUI offers significant benefit in terms of pregnancy outcomes compared with natural cycle or timed intercourse, while reducing associated COH complications such as multiple pregnancies and ovarian hyperstimulation syndrome. Important prognostic indicators of success with IUI include age of patient, duration of infertility, stimulation protocol, infertility etiology, number of cycles, timing of insemination, number of preovulatory follicles on the day of hCG, processed total motile sperm > 10 million, and insemination count > 1 × 106 with > 4% normal spermatozoa. Alternative insemination techniques, such as Fallopian tube sperm perfusion, intracervical insemination, and intratubal insemination, provide no additional benefit compared to IUI. A complete couple workup that includes patient history, physical examination, and clinical and laboratory investigations is mandatory to justify the choice in favor of IUI and guide alternative patient management, while individualizing the treatment protocol according to the patient characteristics with a strict cancelation policy to limit multi-follicular development may help optimize IUI

Early intrauterine embryonic development in Khawia sinensis Hsü, 1935 (Cestoda, Caryophyllidea, Lytocestidae), an invasive tapeworm of carp (Cyprinus carpio): an ultrastructural study.

PubMed

Bruňanská, Magdaléna; Mackiewicz, John S; Młocicki, Daniel; Swiderski, Zdzisław; Nebesářová, Jana

2012-02-01

Intrauterine embryonic development in the caryophyllidean tapeworm Khawia sinensis has been investigated using transmission electron microscopy and cytochemical staining with periodic acid-thiosemicarbazide-silver proteinate for glycogen. Contrary to previous light microscopy findings that reported the release of non-embryonated eggs of K. sinenesis to the external environment, the present study documents various stages of embryonation (ovoviviparity) within the intrauterine eggs of this cestode. At the initial stage of embryonic development, each fertilised oocyte is accompanied by several vitellocytes that become enclosed within the operculate, electrondense shell. Cleavage divisions result in formation of blastomeres (up to about 24 cells) of various sizes. Mitotic divisions and apparent rosette arrangment of the blastomeres, the latter atypical within the Eucestoda, are observed for the first time in the intrauterine eggs of K. sinenesis. The early embryo enclosed within the electrondense shell is surrounded by a thin membraneous layer which in some enlarged regions shows presence of nuclei. Simultaneously to multiplication and differentiation, some of the blastomeres undergo deterioration. A progressive degeneration of the vitellocytes within eggs provides nutritive reserves, including lipids, for the developing embryo. The possible significance of this atypical timing of the intrauterine embryonic development to (1) the ecology of K. sinensis and that of a recent introduction of another invasive tapeworm, the caryophyllidean Atractolytocestus huronensis Anthony, 1958 to Europe; and (2) the affiliation of caryophyllideans with other lower cestodes, are discussed.

Placental Nutrient Transport and Intrauterine Growth Restriction

PubMed Central

Gaccioli, Francesca; Lager, Susanne

2016-01-01

Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as maternal undernutrition, pre-eclampsia, young maternal age, high altitude and infection. PMID:26909042

Intrauterine exposure to tobacco and executive functioning in high school.

PubMed

Rose-Jacobs, Ruth; Richardson, Mark A; Buchanan-Howland, Kathryn; Chen, Clara A; Cabral, Howard; Heeren, Timothy C; Liebschutz, Jane; Forman, Leah; Frank, Deborah A

2017-07-01

Executive functioning (EF), an umbrella construct encompassing gradual maturation of cognitive organization/management processes, is important to success in multiple settings including high school. Intrauterine tobacco exposure (IUTE) correlates with negative cognitive/behavioral outcomes, but little is known about its association with adolescent EF and information from real-life contexts is sparse. We evaluated the impact of IUTE on teacher-reported observations of EF in urban high school students controlling for covariates including other intrauterine and adolescent substance exposures. A prospective low-income birth cohort (51% male; 89% African American/Caribbean) was followed through late adolescence (16-18 years old). At birth, intrauterine exposures to cocaine and other substances (52% cocaine, 52% tobacco, 26% marijuana, 26% alcohol) were identified by meconium and/or urine assays, and/or maternal self-report. High school teachers knowledgeable about the student and unaware of study aims were asked to complete the Behavior Rating Inventory of Executive Functioning-Teacher Form (BRIEF-TF) annually. Teachers completed at least one BRIEF-TF for 131 adolescents. Multivariable analyses included controls for: demographics; intrauterine cocaine, marijuana, and alcohol exposures; early childhood exposures to lead; and violence exposure from school-age to adolescence. IUTE was associated with less optimal BRIEF-TF Behavioral Regulation scores (p <0.05). Other intrauterine substance exposures did not predict less optimal BRIEF-TF scores, nor did exposures to violence, lead, nor adolescents' own substance use. IUTE is associated with offspring's less optimal EF. Prenatal counseling should emphasize abstinence from tobacco, as well as alcohol and illegal substances. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinico-hysteroscopic analysis of severe intrauterine adhesions among Nigerian infertile women.

PubMed

Ugboaja, Joseph Odirichukwu; Oguejiofor, Charlotte Blanche; Igwegbe, Anthony Osita

2017-01-01

Severe intrauterine adhesions are difficult to manage and are associated with poor reproductive outcomes following treatment. The objective was to study the clinical presentation and hysteroscopic findings of severe intrauterine adhesions seen at hysteroscopy in two fertility/gynaecological endoscopy units in Nigeria. A prospective study of 19 out of 76 women managed for intrauterine adhesions in our units. Data were analyzed with STATA software, version 12.0 SE (Stata Corporation, TX, USA). Severe intrauterine adhesion accounted for 19 (25.0%) of 76 cases of intrauterine adhesions managed during the period. This constituted 11.9% of 160 infertile women who had diagnostic hysteroscopies in our units over the study period. The mean duration of symptom was 4.2 years +/-3.2. Amenorrhea in association with infertility (68.4%) was the main presenting complaint. Secondary dysmenorrhea and cyclical abdominal pain were found in 10.8% and 31.6% of the women respectively. The main aetiological events were complicated caesarean section (42.1%) and abdominal myomectomy (26.3%). The adhesions were mainly dense (52.6%) and multiple (94.7%) with complete involvement of the uterine cavity in all the cases. Obliterative lesions were seen in 63.2% of the women. The main clinical presentation of severe IUA was amenorrhea and infertility while the major risk factors were complicated caesarean section and myomectomy. The adhesions were mainly multiple, dense, obliterative and complete.

Differential Expression of Programmed Cell Death on the Follicular Development in Normal and Miniature Pig Ovary

PubMed Central

Kim, Sang Hwan; Min, Kwan Sik; Kim, Nam Hyung; Yoon, Jong Taek

2012-01-01

Follicles are important in oocyte maturation. Successful estrous cycle requires remodeling of follicular cells, and proper execution of programmed cell death is crucial for normal follicular development. The objectives of the present study were to understand programmed cell death during follicle development, to analyze the differential follicle development patterns, and to assess the patterns of apoptosis and autophagy expression during follicle development in normal and miniature pigs. Through the analysis of differential patterns of programmed cell death during follicular development in porcine, MAP1LC3A, B and other autophagy-associated genes (ATG5, mTOR, Beclin-1) were found to increase in normal pigs, while it decreased in miniature pigs. However, for the apoptosis-associated genes, progression of genes during follicular development increased in miniature pigs, while it decreased in normal pigs. Thus, results show that normal and miniature pigs showed distinct patterns of follicular remodeling manifesting that programmed cell death largely depends on the types of pathway during follicular development (Type II or autophagy for normal pigs and Type I or apoptosis for miniature pigs). PMID:23056260

Intrauterine contraception in Saint Louis: A Survey of Obstetrician and Gynecologists’ knowledge and attitudes

PubMed Central

Madden, Tessa; Allsworth, Jenifer E.; Hladky, Katherine J.; Secura, Gina M.; Peipert, Jeffrey F.

2009-01-01

Background Many obstacles to intrauterine contraception use exist, including provider and patient misinformation, high upfront cost, and clinician practice patterns. The aim of our study was to investigate knowledge and attitudes about intrauterine contraception among obstetricians and gynecologists in the area of Saint Louis. Study Design We mailed a self-administered, anonymous survey to 250 clinicians who provide obstetric and gynecologic care in Saint Louis City and County which included questions about demographics, training, family planning visits, and intrauterine contraceptive knowledge and use. Results The overall survey response rate among eligible clinicians was 73.7%. Clinicians who had recently finished training or saw higher numbers of contraceptive patients per week were more likely to insert intrauterine contraception than clinicians who completed training prior to 1989 or saw fewer contraceptive patients. Several misconceptions among clinicians were identified, including an association between intrauterine contraceptives and an elevated risk of pelvic inflammatory disease. Conclusions Physician misconceptions about the risks of intrauterine contraception continue to occur. Improved clinician education is greatly needed to facilitate the use of these highly effective, long-acting, reversible methods of contraception. PMID:20103447

Intrauterine devices and risk of uterine perforation: current perspectives

PubMed Central

Rowlands, Sam; Oloto, Emeka; Horwell, David H

2016-01-01

Uterine perforation is an uncommon complication of intrauterine device insertion, with an incidence of one in 1,000 insertions. Perforation may be complete, with the device totally in the abdominal cavity, or partial, with the device to varying degrees within the uterine wall. Some studies show a positive association between lactation and perforation, but a causal relationship has not been established. Very rarely, a device may perforate into bowel or the urinary tract. Perforated intrauterine devices can generally be removed successfully at laparoscopy. PMID:29386934

Ruptured ectopic pregnancy in a patient with a recent intrauterine abortion.

PubMed

Nugent, P J

1992-01-01

The case of a 33-year-old woman who presented with abdominal pain referable to the lower abdomen is discussed. She had had an uncomplicated intrauterine abortive procedure two weeks earlier. It was determined that a ruptured ectopic pregnancy was the etiology of her abdominal pain. The rare phenomenon of combined intrauterine and extrauterine pregnancy is discussed.

Assessment of Risk Factors of Intrauterine Adhesions in Patients With Induced Abortion and the Curative Effect of Hysteroscopic Surgery.

PubMed

Mo, Xiaoliang; Qin, Guirong; Zhou, Zhoulin; Jiang, Xiaoli

2017-10-03

To explore the risk factors for intrauterine adhesions in patients with artificial abortion and clinical efficacy of hysteroscopic dissection. 1500 patients undergoing artificial abortion between January 2014 and June 2015 were enrolled into this study. The patients were divided into two groups with or without intrauterine adhesions. Univariate and Multiple logistic regression were conducted to assess the effects of multiple factors on the development of intrauterine adhesions following induced abortion. The incidence rate for intrauterine adhesions following induced abortion is 17.0%. Univariate showed that preoperative inflammation, multiple pregnancies and suction evacuation time are the influence risk factors of intrauterine adhesions. Multiple logistic regression demonstrates that multiple pregnancies, high intrauterine negative pressure, and long suction evacuation time are independent risk factors for the development of intrauterine adhesions following induced abortion. Additionally, intrauterine adhesions were observed in 105 mild, 80 moderate, and 70 severe cases. The cure rates for these three categories of intrauterine adhesions by hysteroscopic surgery were 100.0%, 93.8%, and 85.7%, respectively. Multiple pregnancies, high negative pressure suction evacuation and long suction evacuation time are independent risk factors for the development of intrauterine adhesions following induced abortions. Hysteroscopic surgery substantially improves the clinical outcomes of intrauterine adhesions.

Intrauterine contraception in nulliparous women: a prospective survey

PubMed Central

Kutler, Beth A

2016-01-01

Background Intrauterine contraception is a first-line option for young women, yet relatively few prospective studies have been performed in nulliparous women using currently available devices, and many providers are still reluctant to provide this option. Methods Between January 2012 and June 2014, 109 nulliparous women, aged 18–30 years, who had an intrauterine device (IUD) placed at a student health clinic [88 levonorgestrel-intrauterine system (LNG-IUS) users and 21 Cu T 380A (IUD) users] were surveyed at 1, 6, 12 and 18 months after insertion. Results Overall satisfaction was high; at follow-up survey 83% of 100 women (mean use 13.4 months) were ‘happy’ or ‘very happy’ with their IUD, and there were no differences in satisfaction between the two IUD types. Some 75% of participants stated that the insertion procedure went ‘very well’, despite 78% rating insertion pain as moderate to severe, and 46% experiencing vasovagal symptoms. The 12-month continuation rate was 89%, with discontinuations for expulsion (3%), side effects (6%), lack of anticipated benefit (1%) and pregnancy (1%). Users of the Cu T 380A were more likely to have heavy menses (74% vs 2%; p<0.0001) or moderate to severe cramping (68% vs 20%; p=0.0002) compared with LNG-IUS users. There were no uterine perforations or diagnoses of pelvic inflammatory disease. The rate of failed insertions during the study period was 6.2%. Conclusions Despite significant symptoms with insertion, intrauterine contraception is safe, effective and ultimately well tolerated in nulliparous women and should be provided to this population in both university and community health settings. PMID:25854550

Routine provision of intrauterine contraception at elective cesarean section in a national public health service: a service evaluation.

PubMed

Heller, Rebecca; Johnstone, Anne; Cameron, Sharon T

2017-09-01

We conducted a prospective health service evaluation to assess the feasibility and acceptability of routinely offering insertion of intrauterine contraception at cesarean section in a maternity setting in the UK. One month before scheduled cesarean section, women were sent information about postpartum contraception including the option of insertion of an intrauterine contraception at cesarean. Women choosing intrauterine contraception (copper intrauterine device or levonorgestrel intrauterine system) were followed up in person at six weeks, and telephone contact was made at three, six and 12 months postpartum. Our main outcome measures were uptake of intrauterine contraception and complications by six weeks. Secondary outcomes were continuation and satisfaction with intrauterine contraception at 12 months. 120/877 women opted to have intrauterine contraception (13.7%), of which 114 were fitted. By six weeks, there were seven expulsions (6.1%). The expulsion rate by one year was 8.8%. There were no cases of uterine perforations and one case of infection (0.8%). Follow-up rates were 82.5% at 12 months, and continuation rates with intrauterine contraception at 12 months were 84.8% of those contacted. At 12 months, 92.7% of respondents asked were either 'very' or 'fairly' happy with their intrauterine contraception. Routine provision of intrauterine contraception at elective cesarean for women in a public maternity service is feasible and acceptable to women. It is associated with good uptake and good continuation rates for the first year. This could be an important strategy to increase use of intrauterine contraception and prevent short inter-pregnancy intervals and unintended pregnancies. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Intrauterine air impairs embryonic postimplantation development in mice.

PubMed

Liu, Ruonan; Li, Yimeng; Miao, Yanping; Wei, Yanhui; Guan, Mo; Zhou, Rongyan; Li, Xiangyun

2017-12-01

Although most embryologists load air bubbles into the catheter along with embryos during embryo transfer, the effects of these air bubbles on embryo transfer success rate are not clear. Air bubbles were nonsurgically injected into unilateral uterine horns of mice to demonstrate the negative effects of intrauterine air bubbles on embryonic development. Our data showed that when air bubbles are nonsurgically injected into unilateral uterine horns of pregnant 4days mice the litter size is significantly decreased. Four days after the introduction of air, abnormal decidua and dead conceptuses were detected in the uterine horns receiving the air bubbles. In addition, intrauterine air also significantly impaired murine embryo transfer success rates, and induced an increase in endometrial capillary permeability and decidualization in mice on day 4 of pseudopregnancy. These results strongly indicated that the air bubbles loaded into embryo transfer catheters to bracket the embryo-containing medium may have negative effect on embryonic implantation and development. Intrauterine air impaired murine embryonic postimplantation development, and this provided some clues for improving embryo transfer techniques in human. Copyright © 2017 Elsevier B.V. All rights reserved.

[The significance of electronic CTG for intrauterine volvulus in the 32nd week of gestation].

PubMed

Schiermeier, S; Reinhard, J; Westhof, G; Hatzmann, W

2008-02-01

Intrauterine intestinal volvulus is a difficult diagnosis to make, but has life-threatening implications for the fetus. We present a case of vulvulus without malrotation in a single fetus revealed in the 32nd gestation week in a 44-year-old woman. The presenting complaint of this patient was reduced fetal movements. Ultrasound examination showed a normal result except for a dilated stomach. Doppler ultrasound results were within the normal range. Computed cardiotocography (CTG) showed pathological results for acceleration and suspect values for variability. Short-term variability (STV) was at 2.80 ms. Due to the pathological computed CTG results a Caesarian section was carried out. The newborn received prompt postnatal surgical treatment and continues to be in good overall condition.

Intrauterine growth restriction in infants of less than thirty-two weeks' gestation: associated placental pathologic features.

PubMed

Salafia, C M; Minior, V K; Pezzullo, J C; Popek, E J; Rosenkrantz, T S; Vintzileos, A M

1995-10-01

Our purpose was to describe placental lesions associated with normal and abnormal fetal growth in infants delivered for obstetric indications at < 32 weeks' gestation. Maternal and neonatal charts and placental tissues from 420 consecutive nonanomalous live-born singleton infants delivered at < 32 weeks' gestation with accurate gestational dates were retrospectively studied. Excluded were cases with maternal diabetes, chronic hypertension, hydrops fetalis, diagnosed congenital viral infection, and placenta previa, leaving four primary indications for delivery: preeclampsia, preterm labor, premature rupture of membranes, and nonhypertensive abruptio placentae. The presence and severity of placental lesions was scored by a pathologist blinded to clinical data. Birth weight and length percentiles were calculated from published nomograms. Asymmetric intrauterine growth retardation (n = 32) was defined as birth weight < 10th percentile with length > 10th percentile and symmetric intrauterine growth retardation (n = 48) as both weight and length < 10th percentile for gestational age. A "growth restriction index" was developed to express a continuum of growth in both length and weight. Contingency tables, analyses of variance, and multiple regression analysis defined significance as p < 0.05 (with corrections for multiple comparisons). A greater proportion of cases with intrauterine growth retardation had lesions of uteroplacental insufficiency (p < 0.001) or chronic villitis (p < 0.02) than did appropriately grown preterm infants. Cases with asymmetric intrauterine growth retardation tended to have more lesions than did cases with appropriate-for-gestational-age infants. Four multiple regression analyses used the growth restriction index as outcome and the histologic lesion that had significant relationships to fetal growth as independent predictors in univariate analyses. Overall, uteroplacental fibrinoid necrosis, circulating nucleated erythrocytes, avascular terminal

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

PubMed

Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

2016-06-01

Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0

Maternal amino acid supplementation for intrauterine growth restriction

PubMed Central

Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J

2011-01-01

Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387

Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh

2012-04-13

Highlights: Black-Right-Pointing-Pointer Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. Black-Right-Pointing-Pointer Neuronal glycosylation in injury and after ChABC treatment is unknown. Black-Right-Pointing-Pointer In silico mining verified that glyco-related genes were differentially regulated after SCI. Black-Right-Pointing-Pointer In vitro model system revealed abnormal sialylation in an injured environment. Black-Right-Pointing-Pointer The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellularmore » matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually {alpha}-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8

Nd-YAG laser with a fibertom system in the treatment of intrauterine lesions

NASA Astrophysics Data System (ADS)

Wilczak, Maciej; Wozniak, Jakub; Sajdak, Stefan; Dydowicz, Piotr; Opala, Tomasz; Cwojdzinski, Marek; Pisarski, Tadeusz

1997-10-01

The results of 31 Nd:YAG hysteroscopic laser surgeries done in the Department of Reproduction, Institute of Gynecology and obstetrics, Karon Marcinkowski School of Medical Sciences, Poznan, Poland were describe. In nine patients the uterine septa and in 22 women the intrauterine adhesion were recognized. Hysteroscopy is a very useful and reliable method in diagnosis and treatment of intrauterine lesions reducing fertility. The laser resection of intrauterine lesions in women with malreproduction is an efficient and safe method. The fertility and parity after laser surgery are highly improved.

Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.

PubMed Central

Woods, C G; Leversha, M; Rogers, J G

1995-01-01

We report an infant with pre- and postnatal microcephaly and growth retardation, a distinctive face, and developmental delay. The initial diagnosis was of Seckel syndrome. He became pancytopenic at 16 months and died soon after. His bone marrow was of normal cellularity but had a small lymphocyte infiltration. Increased spontaneous chromosome breakage was seen in blood and fibroblasts. Mitomycin C induced chromosome damage was increased and comparable to that seen in Fanconi anaemia. Reports of similar patients are reviewed. This entity of severe intrauterine growth retardation and increased mitomycin C sensitivity is hypothesised to be a distinct chromosome breakage syndrome. Images PMID:7643362

Intrauterine growth restriction is associated with persistent aortic wall thickening and glomerular proteinuria during infancy

PubMed Central

Zanardo, Vincenzo; Fanelli, Tiziana; Weiner, Gary; Fanos, Vassilios; Zaninotto, Martina; Visentin, Silvia; Cavallin, Francesco; Trevisanuto, Daniele; Cosmi, Erich

2011-01-01

Low birth weight, caused either by preterm birth or by intrauterine growth restriction, has recently been associated with increased rates of adult renal and cardiovascular disease. Since aortic intima–media thickening is a noninvasive marker of preclinical vascular disease, we compared abdominal aortic intima–media thickness among intrauterine growth restricted and equivalent gestational age fetuses in utero and at 18 months of age. The relationship between intrauterine growth restriction, fetal aortic thickening, and glomerular function during infancy was measured by enrolling 44 mothers with single-fetus pregnancies at 32 weeks gestation: 23 growth restricted and 21 of appropriate gestational age as controls. Abdominal aortic intima–media thickness was measured by ultrasound at enrollment and again at 18 months of age. Fetuses with intrauterine growth restriction had significantly higher abdominal aortic intima–media thickness compared with age controls when measured both in utero and at 18 months. At 18 months, the median urinary microalbumin and median albumin–creatinine ratio were significantly higher in those infants who experienced intrauterine growth restriction compared to the controls. Our results show that intrauterine growth restriction is associated with persistent aortic wall thickening and significantly higher microalbuminuria during infancy. PMID:21490588

Intrauterine contraception in nulliparous women: a prospective survey.

PubMed

Hall, Alexandra M; Kutler, Beth A

2016-01-01

Intrauterine contraception is a first-line option for young women, yet relatively few prospective studies have been performed in nulliparous women using currently available devices, and many providers are still reluctant to provide this option. Between January 2012 and June 2014, 109 nulliparous women, aged 18-30 years, who had an intrauterine device (IUD) placed at a student health clinic [88 levonorgestrel-intrauterine system (LNG-IUS) users and 21 Cu T 380A (IUD) users] were surveyed at 1, 6, 12 and 18 months after insertion. Overall satisfaction was high; at follow-up survey 83% of 100 women (mean use 13.4 months) were 'happy' or 'very happy' with their IUD, and there were no differences in satisfaction between the two IUD types. Some 75% of participants stated that the insertion procedure went 'very well', despite 78% rating insertion pain as moderate to severe, and 46% experiencing vasovagal symptoms. The 12-month continuation rate was 89%, with discontinuations for expulsion (3%), side effects (6%), lack of anticipated benefit (1%) and pregnancy (1%). Users of the Cu T 380A were more likely to have heavy menses (74% vs 2%; p<0.0001) or moderate to severe cramping (68% vs 20%; p=0.0002) compared with LNG-IUS users. There were no uterine perforations or diagnoses of pelvic inflammatory disease. The rate of failed insertions during the study period was 6.2%. Despite significant symptoms with insertion, intrauterine contraception is safe, effective and ultimately well tolerated in nulliparous women and should be provided to this population in both university and community health settings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Intrauterine growth restriction and hypospadias: is there a connection?

PubMed Central

2014-01-01

Hypospadias is one of the most common congenital malformations of the genitourinary tract in males. It is an incomplete fusion of urethral folds early in fetal development and may be associated with other malformations of the genital tract. The etiology is poorly understood and may be hormonal, genetic, or environmental, but most often is idiopathic or multifactorial. Among many possible risk factors identified, of particular importance is low birth weight, which is defined in various ways in the literature. No mechanism has been identified for the association of low birth weight and hypospadias, but some authors propose placental insufficiency as a common inciting factor. Currently, there is no standardized approach for evaluating children with hypospadias in the setting of intrauterine growth restriction. We reviewed the available published literature on the association of hypospadias and growth restriction to determine whether it should be considered a separate entity within the category of disorders of sexual differentiation. PMID:25337123

Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy

PubMed Central

Lähteenmäki, Pekka; Haukkamaa, Maija; Puolakka, Jukka; Riikonen, Ulla; Sainio, Susanna; Suvisaari, Janne; Nilsson, Carl Gustaf

1998-01-01

Objectives: To assess whether the levonorgestrel intrauterine system could provide a conservative alternative to hysterectomy in the treatment of excessive uterine bleeding. Design: Open randomised multicentre study with two parallel groups: a levonorgestrel intrauterine system group and a control group. Setting: Gynaecology departments of three hospitals in Finland. Subjects: Fifty six women aged 33-49 years scheduled to undergo hysterectomy for treatment of excessive uterine bleeding. Interventions: Women were randomised either to continue with their current medical treatment or to have a levonorgestrel intrauterine system inserted. Main outcome measure: Proportion of women cancelling their decision to undergo hysterectomy. Results: At 6 months, 64.3% (95% confidence interval 44.1 to 81.4%) of the women in the levonorgestrel intrauterine system group and 14.3% (4.0 to 32.7%) in the control group had cancelled their decision to undergo hysterectomy (P<0.001). Conclusions: The use of the levonorgestrel intrauterine system is a good conservative alternative to hysterectomy in the treatment of menorrhagia and should be considered before hysterectomy or other invasive treatments. PMID:9552948

Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction.

PubMed

Szentpéteri, Imre; Rab, Attila; Kornya, László; Kovács, Péter; Joó, József Gábor

2013-07-01

In this study, we describe changes in gene expression pattern of vascular endothelial growth factor (VEGF)-A in human placenta obtained from pregnancies with intrauterine growth restriction using placenta from normal pregnancies as control. We compared gene expression of VEGF-A in placental samples from Intrauterine growth restriction (IUGR) pregnancies versus placenta obtained from normal pregnancies. Among potential confounders, important clinical informations were also analyzed. In the IUGR group, the VEGF-A gene was overexpressed compared to the normal pregnancy group (Ln 2(α)β-actin: 1.32; Ln 2(α)GADPH: 1.56). There was no correlation between the degree of growth restriction and VEGF-A gene expression (Ln 2(α)(0-5)percentile: 0.58; Ln 2(α)(5-10)percentile: 0.64). Within the IUGR group, there was a trend toward a positive correlation between placental VEGF-A gene activity and gestational age at delivery (Ln 2(α)< 33 weeks: 1.09; Ln 2(α)33-37 weeks: 1.27; Ln 2(α)> 37 weeks: 1.35). Our findings suggest that the increase in placental expression of the VEGF-A gene and the resultant stimulation of angiogenesis are a response to hypoxic environment developing in the placental tissue in IUGR. Thus, it appears to be a secondary event rather than a primary factor in the development of IUGR There is a trend toward a positive correlation between gestational age and placental VEGF-A gene activity.

Inbred guinea pig model of intrauterine infection with cytomegalovirus.

PubMed

Griffith, B P; McCormick, S R; Booss, J; Hsiung, G D

1986-01-01

Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.

Inherited thrombophilia in pregnant women with intrauterine growth restriction.

PubMed

Coriu, Letitia; Copaciu, Elena; Tulbure, Dan; Talmaci, Rodica; Secara, Diana; Coriu, Daniel; Cirstoiu, Monica

2014-12-01

Intrauterine growth restriction (IUGR) is a major cause of fetal morbidity and mortality during pregnancy. The role of mutation in the factor V gene, prothrombin gene, MTHFR gene, as risk factors for intrauterine growth restriction during pregnancy, is not very well known so far. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: intrauterine growth restriction, preeclampsia, recurrent pregnancy loss or maternal venous thromboembolism, who were admitted in Bucharest Emergency University Hospital, during the period January 2010 to July 2014. Genetic testing was performed for all the cases to detect: factor V Leiden mutation, G20210A mutation in the prothrombin gene, C677T mutation and A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. Blood samples were obtained as soon as the diagnosis of intrauterine growth restriction was established with ultrasonography. The following gene mutations were associated with increased risk of IUGR: G20210A prothrombin gene mutation (OR 4.81, 95% CI 1.05 - 2.22, p= 0.043), G1691A factor V gene mutation (factor V Leiden) (OR 1.58, 95% CI 0.61 - 4.080, p= 0.347), C677T MTHFR gene mutation (OR 1.61, 95% CI 0.79 to 3.26, p= 0.186), compound heterozygous MTHFR C677T and A1298C (OR 1.66, 95% CI 0.81- 3.42, p= 0.169). Particularly, for G20210A prothrombin gene mutation we found statistically significant risk (p≤0.05) of IUGR.

Left ventricular dimensions, systolic functions, and mass in term neonates with symmetric and asymmetric intrauterine growth restriction.

PubMed

Cinar, Bahar; Sert, Ahmet; Gokmen, Zeynel; Aypar, Ebru; Aslan, Eyup; Odabas, Dursun

2015-02-01

Previous studies have demonstrated structural changes in the heart and cardiac dysfunction in foetuses with intrauterine growth restriction. There are no available data that evaluated left ventricular dimensions and mass in neonates with symmetric and asymmetric intrauterine growth restriction. Therefore, we aimed to evaluate left ventricular dimensions, systolic functions, and mass in neonates with symmetric and asymmetric intrauterine growth restriction. We also assessed associated maternal risk factors, and compared results with healthy appropriate for gestational age neonates. In all, 62 asymmetric intrauterine growth restriction neonates, 39 symmetric intrauterine growth restriction neonates, and 50 healthy appropriate for gestational age neonates were evaluated by transthoracic echocardiography. The asymmetric intrauterine growth restriction group had significantly lower left ventricular end-systolic and end-diastolic diameters and posterior wall diameter in systole and diastole than the control group. The symmetric intrauterine growth restriction group had significantly lower left ventricular end-diastolic diameter than the control group. All left ventricular dimensions were lower in the asymmetric intrauterine growth restriction neonates compared with symmetric intrauterine growth restriction neonates (p>0.05), but not statistically significant except left ventricular posterior wall diameter in diastole (3.08±0.83 mm versus 3.54 ±0.72 mm) (p<0.05). Both symmetric and asymmetric intrauterine growth restriction groups had significantly lower relative posterior wall thickness (0.54±0.19 versus 0.48±0.13 versus 0.8±0.12), left ventricular mass (9.8±4.3 g versus 8.9±3.4 g versus 22.2±5.7 g), and left ventricular mass index (63.6±29.1 g/m2 versus 54.5±24.4 g/m2 versus 109±28.8 g/m2) when compared with the control group. Our study has demonstrated that although neonates with both symmetric and asymmetric intrauterine growth restriction had lower left

Head-to-cervix force: an important physiological variable in labour. 1. The temporal relation between head-to-cervix force and intrauterine pressure during labour.

PubMed

Allman, A C; Genevier, E S; Johnson, M R; Steer, P J

1996-08-01

To investigate the relation between the rise in intrauterine pressure and rise in fetal head to cervix force in normal, slow and induced labour. Prospective observational study. The labour ward of a London teaching hospital. Forty patients were recruited from the antenatal clinic and labour ward of a West London Hospital. Five had normal onset and progression of labour, 14 had slow progression of labour and 21 had induced onset of labour. Intrauterine pressure and head-to-cervix force was measured simultaneously using an intrauterine pressure catheter and a specially designed four sensor head-to-cervix force probe. For each contraction of each labour, scattergrams of force by pressure were plotted. Three patterns were observed. When the rise in pressure preceded the rise in force, a positive 'loop' was generated. When the rise in pressure and force occurred simultaneously a linear pattern was generated (a neutral 'loop'). When the rise in pressure lags the rise in force, a negative 'loop' was generated. In normally progressive labour the distribution of loops was 29.1%, 22.6% and 48.3%, respectively, in slow labour the distribution was 26.1%, 14.1% and 59.8% and in induced labour the distribution was 33.8%, 14.4% and 51.8%. These distributions were not statistically different. However, a higher proportion of negative loops was observed in labours augmented with oxytocin compared to those receiving no oxytocin (MW-U = 87, P = 0.036). No differences were observed comparing parity, use of PGE2, epidural analgesia, or mode of delivery. Contraction frequency (number/10 minutes) was inversely correlated to the percentage of negative loops (rs = -0.34, P = 0.033) and positively correlated with percentage of positive loops (rs = 0.36, P = 0.027). This is the first report of the temporal relation between intrauterine pressure and head-to-cervix force in labour. The most common pattern is that the rise in pressure lags the rise in force, suggesting that a seal has to be

Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

PubMed

Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

2010-11-02

Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; P<0.0001). Flow-independent vasodilatation was similar among all groups. Similarly, the radial augmentation index was significantly increased among women with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher

Effects of heritability, shared environment, and nonshared intrauterine conditions on child and adolescent BMI.

PubMed

Salsberry, Pamela J; Reagan, Patricia B

2010-09-01

Heritability studies of BMI, based upon twin samples, have identified genetic and shared environmental components of BMI, but have been largely silent about the nonshared environmental factors. Intrauterine factors have been identified as having significant long-term effects on BMI and may be a critical source of nonshared environmental influence. Extant studies based on samples of either unrelated individuals or twins cannot separate the effects of genetics, shared environments, and nonshared intrauterine conditions because the one lacks variation in the degree of relatedness and the other has insufficient variation in intrauterine conditions. This study improves upon these prior studies by using a large, sibling-based sample to examine heritability, shared environmental, and nonshared intrauterine influences on BMI during two age periods in childhood (6-8 years; 12-14 years). The primary interest was in determining the effects of the intrauterine environment on BMI as a component of the nonshared environment and in determining whether there were sex-specific differences in heritability and/or in the intrauterine factors. These were estimated using regression-based techniques introduced by DeFries and Fulker. Heritability of BMI was estimated to be 0.20-0.28 at 6-8 years and 0.46-0.61 at 12-14 years. Differences in heritability were found at 12-14 years between same-sex as compared to mixed-sex pairs. The shared environmental effect was significant at 6-8 years but insignificant at 12-14 years. Differences in birth weight were significant in all groups at 6-8 years suggesting long-term effects of the nonshared intrauterine environment; at 12-14 years, birth weight was no longer significant for girls.

Sequence of Fibrinogen Proteolysis and Platelet Release after Intrauterine Infusion of Hypertonic Saline

PubMed Central

Nossel, H. L.; Wasser, J.; Kaplan, K. L.; Lagamma, K. S.; Yudelman, I.; Canfield, R. E.

1979-01-01

Plasma fibrinopeptide B (Bβ1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bβ1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bβ1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bβ1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bβ42)-alanine (Bβ43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (βTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases βTG and PF4 from

A study to examine the relationship between metritis severity and depletion of oxytetracycline in plasma and milk after intrauterine infusion.

PubMed

Gorden, P J; Ydstie, J A; Kleinhenz, M D; Wulf, L W; Gehring, R; Lee, C J; Wang, C; Coetzee, J F

2016-10-01

severity scores of 3 or 4) at the initiation of treatment were significantly and positively correlated with higher milk OTC concentrations at the second [time (T)9 h; r=0.43], fourth (T25 h; r=0.42), and fifth milking following treatment (T33 h; r=0.38) compared with cows with normal vaginal discharge. We also observed a positive correlation between initial metritis score and milk maximum concentration (r=0.36) and milk area under the concentration curve (r=0.36). Given that intrauterine administration of OTC is an extra-label therapy, dairy producers should consult with their veterinarian to ensure that milk is being tested at or below the established tolerance for OTC. This will ensure that violative drug residues do not enter the human food supply. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Intrauterine cardiomyopathy and cardiac mitochondrial proliferation in mitochondrial trifunctional protein (TFP) deficiency.

PubMed

Spiekerkoetter, Ute; Mueller, Martina; Cloppenburg, Eva; Motz, Reinald; Mayatepek, Ertan; Bueltmann, Burkhard; Korenke, Christoph

2008-08-01

Because of a switch in energy-producing substrate utilization from glucose in the fetal period to fatty acids postnatally, intrauterine morbidity of fatty acid oxidation defects has widely been denied. We report the intrauterine development of severe cardiomyopathy in a child with mitochondrial trifunctional protein deficiency after 27 weeks of gestation. The child was born at 31 weeks of gestation and died on day 3 of life. Severe cardiac mitochondrial proliferation was observed. Molecular analysis of both TFP genes was performed and confirmed a homozygous mutation in the TFP alpha-subunit introducing a stop codon at amino acid position 256 (g.871C>T, p.R256X). Despite severe intrauterine decompensation in our patient, no HELLP-syndrome or acute fatty liver of pregnancy was observed in the mother. In the pathogenesis of maternal HELLP-syndrome, toxic effects of accumulating long-chain hydroxy-acyl-CoAs or long-chain hydroxy-acylcarnitines are suspected. In our patient, acylcarnitine analysis on day 2 of life during severest metabolic decompensation did not reveal massive accumulation of long-chain hydroxy-acylcarnitines in blood, suggesting other pathogenic factors than toxic effects. The most important pathogenic mechanism for the development of intrauterine cardiomyopathy appears to be significant cardiac energy deficiency. In conclusion, our report implicates that fatty acid oxidation does play a significant role during intrauterine development with special regard to the heart. Severe cardiac mitochondrial proliferation in TFP deficiency suggests pathophysiologically relevant energy deficiency in this condition.

The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis.

PubMed

Osman, A; Pundir, J; Elsherbini, M; Dave, S; El-Toukhy, T; Khalaf, Y

2016-09-01

In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

PubMed

Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D

2017-02-15

Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group

Intrauterine Linear Echogenicities in the Gravid Uterus: What Radiologists Should Know.

PubMed

Jensen, Kyle K; Oh, Karen Y; Kennedy, Anne M; Sohaey, Roya

2018-01-01

Intrauterine linear echogenicity (ILE) is a common ultrasonographic finding in the gravid uterus and has variable causes and variable maternal and fetal outcomes. Correctly categorizing ILE during pregnancy is crucial for guiding surveillance and advanced imaging strategies. Common causes of ILE include membranes in multiple gestations, uterine synechiae with amniotic sheets, and uterine duplication anomalies. Less common causes include circumvallate placenta, chorioamniotic separation, and hemorrhage between membranes. Amniotic band syndrome is a rare but important diagnosis to consider, as it causes severe fetal defects. Imaging findings enable body stalk anomaly, a lethal defect, to be distinguished from amniotic bands, which although destructive are not necessarily lethal. This review describes the key imaging findings used to differentiate the various types of ILE in pregnancy, thus enabling accurate diagnosis and appropriate patient counseling. Online supplemental material is available for this article. © RSNA, 2018.

Does intrauterine crowding affect locomotor development? A comparative study of motor performance, neuromotor maturation and gait variability among piglets that differ in birth weight and vitality

PubMed Central

Aerts, Peter; Prims, Sara; Ayuso, Miriam; Van Cruchten, Steven; Van Ginneken, Chris

2018-01-01

In polytocous species, such as pigs, the growth of an individual fetus is affected by competition from its littermates and the sow. This intrauterine competition greatly influences postnatal traits such as birth weight and vitality (physical strength). A lowered vitality is most often observed among low birth weight piglets. Since it has been argued that locomotion might be key to unraveling vitality-related differences, we compared gait development in piglets with a low birth weight and low vitality (L piglets) with piglets with a normal birth weight and normal vitality (N piglets) by means of spatio-temporal gait analysis during locomotion at self-selected speed. Video recordings of L and N piglets walking along a corridor at ten time points (between birth and 96 h after birth) were made and the footfalls were digitized. Hence, self-selected speed, spatio-temporal characteristics and gait symmetry were analyzed to compare motor performance, neuromotor maturation (motor task, interlimb and intralimb coordination) and gait variability for L and N piglets. The analysis included both absolute and normalized data (according to the dynamic similarity concept), to distinguish neuromotor maturation from effects caused by growth. Results indicate that intrauterine crowding affects locomotion, mainly by impairing growth in utero, with a lowered motor performance during the first 96 h of age as a consequence. A difference in neuromotor skills was also visible, though only for swing and stance duration, implying a difference in neuromotor development in utero. However, further maturation during the first days after birth does not seem to be affected by intrauterine crowding. We can therefore conclude that L piglets might be considered a smaller and fictitious younger version of N piglets. PMID:29689084

Defining and predicting 'intrauterine fetal renal failure' in congenital lower urinary tract obstruction.

PubMed

Ruano, Rodrigo; Safdar, Adnan; Au, Jason; Koh, Chester J; Gargollo, Patricio; Shamshirsaz, Alireza A; Espinoza, Jimmy; Cass, Darrell L; Olutoye, Oluyinka O; Olutoye, Olutoyin A; Welty, Stephen; Roth, David R; Belfort, Michael A; Braun, Michael C

2016-04-01

The aim of this study was to identify predictors of 'intrauterine fetal renal failure' in fetuses with severe congenital lower urinary tract obstruction (LUTO). We undertook a retrospective study of 31 consecutive fetuses with a diagnosis of LUTO in a tertiary Fetal Center between April 2013 and April 2015. Predictors of 'intrauterine fetal renal failure' were evaluated in those infants with severe LUTO who had either a primary composite outcome measure of neonatal death in the first 24 h of life due to severe pulmonary hypoplasia or a need for renal replacement therapy within 7 days of life. The following variables were analyzed: fetal bladder re-expansion 48 h after vesicocentesis, fetal renal ultrasound characteristics, fetal urinary indices, and amniotic fluid volume. Of the 31 fetuses included in the study, eight met the criteria for 'intrauterine fetal renal failure'. All of the latter had composite poor postnatal outcomes based on death within 24 h of life (n = 6) or need for dialysis within 1 week of life (n = 2). The percentage of fetal bladder refilling after vesicocentesis at time of initial evaluation was the only predictor of 'intrauterine fetal renal failure' (cut-off <27 %, area under the time-concentration curve 0.86, 95 % confidence interval 0.68-0.99; p = 0.009). We propose the concept of 'intrauterine fetal renal failure' in fetuses with the most severe forms of LUTO. Fetal bladder refilling can be used to reliably predict 'intrauterine fetal renal failure', which is associated with severe pulmonary hypoplasia or the need for dialysis within a few days of life.

Placental elastography in a murine intrauterine growth restriction model.

PubMed

Quibel, T; Deloison, B; Chammings, F; Chalouhi, G E; Siauve, N; Alison, M; Bessières, B; Gennisson, J L; Clément, O; Salomon, L J

2015-11-01

To compare placental elasticity in normal versus intrauterine growth restriction (IUGR) murine pregnancies using shear wave elastography (SWE). Intrauterine growth restriction was created by ligation of the left uterine artery of Sprague-Dawley rats on E17. Ultrasonography (US) and elastography were performed 2 days later on exteriorized horns after laparotomy. Biparietal diameter (BPD) and abdominal diameter (AD) were measured and compared in each horn. Placental elasticity of each placenta was compared in the right and left horns, respectively, using the Young's modulus, which increases with increasing stiffness of the tissue. Two hundred seventeen feto-placental units from 18 rats were included. Fetuses in the left ligated horn had smaller biometric measurements than those in the right horn (6.7 vs 7.2 mm, p < 0.001, and 9.2 vs 11.2 mm, p < 0.001 for BPD and AD, respectively). Mean fetal weight was lower in the pups from the left than the right horn (1.65 vs 2.11 g; p < 0.001). Mean (SD) Young's modulus was higher for placentas from the left than the right horn (11.7 ± 1.5 kPa vs 8.01 ± 3.8 kPa, respectively; p < 0.001), indicating increased stiffness in placentas from the left than the right horn. There was an inverse relationship between fetal weight and placental elasticity (r = 0.42; p < 0.001). Shear wave elastography may be used to provide quantitative elasticity measurements of the placenta. In our model, placentas from IUGR fetuses demonstrated greater stiffness, which correlated with the degree of fetal growth restriction. © 2015 John Wiley & Sons, Ltd.

Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial.

PubMed

Turok, David K; Leeman, Lawrence; Sanders, Jessica N; Thaxton, Lauren; Eggebroten, Jennifer L; Yonke, Nicole; Bullock, Holly; Singh, Rameet; Gawron, Lori M; Espey, Eve

2017-12-01

Immediate postpartum levonorgestrel intrauterine device insertion is increasing in frequency in the United States, but few studies have investigated the effect of early placement on breast-feeding outcomes. This study examined the effect of immediate vs delayed postpartum levonorgestrel intrauterine device insertion on breast-feeding outcomes. We conducted this noninferiority randomized controlled trial at the University of Utah and the University of New Mexico Health Sciences Centers from February 2014 through March 2016. Eligible women were pregnant and planned to breast-feed, spoke English or Spanish, were aged 18-40 years, and desired a levonorgestrel intrauterine device. Enrolled women were randomized 1:1 to immediate postpartum insertion or delayed insertion at 4-12 weeks' postpartum. Prespecified exclusion criteria included delivery <37.0 weeks' gestational age, chorioamnionitis, postpartum hemorrhage, contraindications to levonorgestrel intrauterine device insertion, and medical complications of pregnancy that could affect breast-feeding. We conducted per-protocol analysis as the primary approach, as it is considered the standard for noninferiority studies; we also report the alternative intent-to-treat analysis. We powered the study for the primary outcome, breast-feeding continuation at 8 weeks, to detect a 15% noninferiority margin between groups, requiring 132 participants in each arm. The secondary study outcome, time to lactogenesis, used a validated measure, and was analyzed by survival analysis and log rank test. We followed up participants for ongoing data collection for 6 months. Only the data analysis team was blinded to the intervention. We met the enrollment target with 319 participants, but lost 34 prior to randomization and excluded an additional 26 for medical complications prior to delivery. The final analytic sample included 132 in the immediate group and 127 in the delayed group. Report of any breast-feeding at 8 weeks in the immediate

Comparison between scissor and laser resections of intrauterine septa in hysteroscopy

NASA Astrophysics Data System (ADS)

Wilczak, Maciej; Wozniak, Jakub; Cwojdzinski, Marek; Sajdak, Stefan; Opala, Tomasz; Pisarski, Tadeusz

1996-03-01

The comparison between results of scissors- and Nd-YAG laser-resection of intrauterine septa in hysteroscopy was shown. In 12 patients the scissors-resection and in 11 women the laser- resection was done. In the group of patients after laser procedure 10 of them were pregnant and 9 delivered healthy children. One missed abortion was diagnosed in the twenty-first week of gestation. After scissors-resection 7 women became pregnant and 5 of them bore mature children. Two of those seven lost their gestation (spontaneous abortions in the nineteenth and twentieth weeks of pregnancy). In the authors' opinion hysteroscopy is a very useful method of diagnostics and therapy of intrauterine septa. The Nd-YAG laser-resection of intrauterine septa seems to be the method with the lowest number of complications. Fertility and parity highly improves after removal of the septa localized in the uterine cavity.

[Pathophysiological changes of umbilical vessels in intrauterine growth restriction].

PubMed

Jakó, Mária; Surányi, Andrea; Kaiser, László; Domokos, Dóra; Gáspár, Róbert; Bártfai, György

2014-12-14

The prevalence of intrauterine growth restriction is 4-5000/100,000 births, and they give the majority of perinatal morbidity. The aim of the authors was to compare the pathomorphologic data and vasoreactivity of umbilical vessels and placenta of small for date newborns to that of the normal pregnancies. Samples of the umbilical cord and placenta were divided into case and control groups. Two 10 cm long segments were cut of the umbilical cord at placental insertion. Tissue bath experiment was performed on umbilical vessels and pathomorphologic data were collected according to the Royal College of Pathologists' protocol. After the development of basal tone, oxytocin and desmopressin did not enhance the vascular contraction, but the pathomorphological and ultrasonographic data were significantly different in the two groups. The results indicate that umbilical vessels might not have oxytocin or vasopressin receptors. The pathomorphologic and flowmetric differences could be the causes of small birth weight.

Will ethylene oxide sterilization influence the application of novel Cu/LDPE nanocomposite intrauterine devices?

PubMed

Xia, Xianping; Wang, Yun; Cai, Shuizhou; Xie, Changsheng; Zhu, Changhong

2009-01-01

Copper/low-density polyethylene (Cu/LDPE) nanocomposite intrauterine device (IUD) is an implanted medicinal device that must be sterilized before use. Sterilization processes act either chemically or physically, leading to a lethal change in the structure or function of organic macromolecules in microorganisms. Given the nature of their action, sterilization might also attack the macromolecules of polymers by the same mechanisms, resulting in changes in surface functional groups and in the internal structure of the polymer. If sterilization leads to changes in surface functional groups and in the internal structure of the LDPE matrix, which will influence the mechanical property and cupric ions release rate of novel Cu/LDPE nanocomposite IUDs, potential clinical application will be limited. Therefore, it is necessary to study the influence of ethylene oxide sterilization on the potential clinical application of novel Cu/LDPE nanocomposite IUDs. The influence of ethylene oxide sterilization on the internal structure, surface functional groups, mechanical property and cupric ions release rate of novel Cu/LDPE nanocomposite IUDs was studied using differential scanning calorimetry, attenuated total reflection Fourier transform infrared spectroscopy, tensile testing and absorbance measurement. Ethylene oxide sterilization did not have any influence on the internal structure, surface functional groups, mechanical property and cupric ions release rate of novel Cu/LDPE nanocomposite intrauterine devices. Ethylene oxide sterilization will not affect the potential application of novel Cu/LDPE nanocomposite IUDs.

Success rates of intrauterine inoculations of layers via the vagina.

PubMed

Landman, W J M; Matthijs, M G R; van Eck, J H H

2013-02-01

Intrauterine inoculation of layer hens has been documented previously in the literature; however, its efficiency has only been assessed on a very small scale. Attempts were therefore made to inoculate 14 experimental groups each consisting of 10 commercial table egg-producing hens intrauterinely with methylene blue. The effect of four variables-oviposition (natural, hormonally induced or not), position of the hen at inoculation (vertical/horizontal), technique to access the uterus (three methods) and inoculation device (four types)-on the success rate of intrauterine inoculation of layers of different breed and age was studied. Immediately after inoculation, hens were euthanized and the presence of methylene blue and perforations in the oviduct were examined. Successful inoculation rates ranged from 0/10 to 10/10. The 100% success rate was obtained in birds without an egg in the uterus, which were restrained in a horizontal position and inoculated with a hard catheter after exposure of the uterovaginal junction. The second best score was obtained in hens inoculated shortly after natural oviposition, maintained in a vertical position and using a corkscrew-shaped saliva ejector after exposure of the vaginal orifice (7/10). In all other groups the success rate was 5/10 or less. Vaginal perforation occurred in none to eight birds per group. It is concluded that intrauterine inoculation of laying hens is only reliable in birds without an egg in the uterus after exposure of the uterovaginal junction. All other methods proved unreliable and often caused vaginal perforations. However, intravaginal inoculation can be performed with 100% accuracy providing the vaginal orifice is exposed.

[Levonorgestrel intrauterine device associated with ureterpyelocaliceal ectasia].

PubMed

Gálvez-Valdovinos, Ramiro; Hernández-López, Rogelio; López-Ambriz, Gustavo; Ramme-Cruzat, Christian

2015-10-01

In 2010, Health Canada, the equivalent to the FDA, reported that the risk of uterine perforation caused by levonorgestrel intrauterine device (IUD) is very serious, warning that its use had increased the number of uterine perforation. A 33 years old patient in who was placed three years before a levonorgestrel IUD; She presented evolution of 10 days with pain in hypogastric and both flanks and chronic constipation of two years; in exploration: moderate abdominal distention, IUD strings were not visible in uterine cervix. With translocated IUD diagnosis, a tomography was performed, finding IUD in abdominal cavity and ureter pyelocalyceal bilateral ectasia; preoperative plasma concentration of levonorgestrel 5.1 nmol/L, leukocytosis of 11,000 cells/mm3, and 20-30 erythrocytes in urine exam. Laparoscopic resection of omentum attached to IUD translocated was performed. One month after surgery plasma levonorgestrel in 0.3 nmol/L, normal urinalysis and hematic cytometry and resolution of the urinary tract ectasia. devices translocated with levonorgestrel, must be removed because the inflammatory reaction caused and the perforation of hollow viscera likelihood, with possibility to produce digestive tract and urinary tract ectasia by its pharmacologic action on smooth muscle.

Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

PubMed

Sah, Shyam Kishor; Kim, Hae Young; Lee, Ji Hae; Lee, Seong-Wook; Kim, Hyung-Sik; Kim, Yeon-Soo; Kang, Kyung-Sun; Kim, Tae-Yoon

2017-06-01

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca 2+ ) concentration. High Ca 2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca 2+ environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca 2+ -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca 2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602. © 2017 AlphaMed Press.

Profound Effect of Profiling Platform and Normalization Strategy on Detection of Differentially Expressed MicroRNAs – A Comparative Study

PubMed Central

Meyer, Swanhild U.; Kaiser, Sebastian; Wagner, Carola; Thirion, Christian; Pfaffl, Michael W.

2012-01-01

Background Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. Methodology/Principal Findings We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. Conclusions/Significance We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of

Suppression of endogenous lipogenesis induces reversion of the malignant phenotype and normalized differentiation in breast cancer

PubMed Central

Schroeder, Barbara; Park, Cheol Hong; Chandra Mohan, KVP; Khurana, Ashwani; Corominas-Faja, Bruna; Cuyàs, Elisabet; Alarcón, Tomás; Kleer, Celina; Menendez, Javier A.; Lupu, Ruth

2016-01-01

The correction of specific signaling defects can reverse the oncogenic phenotype of tumor cells by acting in a dominant manner over the cancer genome. Unfortunately, there have been very few successful attempts at identifying the primary cues that could redirect malignant tissues to a normal phenotype. Here we show that suppression of the lipogenic enzyme fatty acid synthase (FASN) leads to stable reversion of the malignant phenotype and normalizes differentiation in a model of breast cancer (BC) progression. FASN knockdown dramatically reduced tumorigenicity of BC cells and restored tissue architecture, which was reminiscent of normal ductal-like structures in the mammary gland. Loss of FASN signaling was sufficient to direct tumors to a reversed phenotype that was near normal when considering the development of polarized growth-arrested acinar-like structure similar to those formed by nonmalignant breast cells in a 3D reconstituted basement membrane in vitro. This process, in vivo, resulted in a low proliferation index, mesenchymal-epithelial transition, and shut-off of the angiogenic switch in FASN-depleted BC cells orthotopically implanted into mammary fat pads. The role of FASN as a negative regulator of correct breast tissue architecture and terminal epithelial cell differentiation was dominant over the malignant phenotype of tumor cells possessing multiple cancer-driving genetic lesions as it remained stable during the course of serial in vivo passage of orthotopic tumor-derived cells. Transient knockdown of FASN suppressed hallmark structural and cytosolic/secretive proteins (vimentin, N-cadherin, fibronectin) in a model of EMT-induced cancer stem cells (CSC). Indirect pharmacological inhibition of FASN promoted a phenotypic switch from basal- to luminal-like tumorsphere architectures with reduced intrasphere heterogeneity. The fact that sole correction of exacerbated lipogenesis can stably reprogram cancer cells back to normal-like tissue architectures

High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats.

PubMed

Sanders, Marijke W; Fazzi, Gregorio E; Janssen, Ger M J; Blanco, Carlos E; De Mey, Jo G R

2005-07-01

A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria.

Fetal programming of blood pressure in a transgenic mouse model of altered intrauterine environment.

PubMed

Chiossi, Giuseppe; Costantine, Maged M; Tamayo, Esther; Hankins, Gary D V; Saade, George R; Longo, Monica

2016-12-01

Nitric oxide is essential in the vascular adaptation to pregnancy, as knockout mice lacking nitric oxide synthase (NOS3) have abnormal utero-placental perfusion, hypertension and growth restriction. We previously showed with ex vivo studies on transgenic animals lacking NOS3 that adverse intrauterine environment alters fetal programming of vascular reactivity in adult offspring. The current research shows that altered vascular reactivity correlates with higher blood pressure in vivo. Our data suggest that higher blood pressure depends on both genetic background (NOS3 deficiency) and uterine environment, becomes more evident with age (> 7 postnatal weeks), activity and stress, is gender specific (preponderant among males), and can be affected by the sleep-awake cycle. In utero or early postnatal life (< 7 weeks), before onset of hypertension, may represent a potential window for intervention to prevent future cardiovascular disorders. Nitric oxide is involved in the vascular adaptation to pregnancy. Using transgenic animals, we previously showed that adverse intrauterine environment alters vascular reactivity in adult offspring. The aim of our study was to determine if altered vascular programming is associated with abnormal blood pressure (BP) profiles in vivo. Mice lacking a functional endothelial nitric oxide synthase (KO, NOS3 -/- ) and wild-type mice (WT, NOS3 +/+ ) were crossbred to generate homozygous NOS3 -/- (KO), maternally derived heterozygous NOS3 +/- (KOM: mother with adverse intrauterine environment from NOS3 deficiency), paternally derived heterozygous NOS3 +/- (KOP: mother with normal in utero milieu) and NOS3 +/+ (WT) litters. BP was measured in vivo at 7, 14 and 21 weeks of age. After univariate analysis, multivariate population-averaged linear regression models were used to identify factors affecting BP. When compared to WT offspring, systolic (SBP), diastolic (DBP) and mean (MAP) BP progressively increased from KOP, to KOM, and peaked among KO

lncRNA requirements for mouse acute myeloid leukemia and normal differentiation

PubMed Central

Knott, Simon RV; Munera Maravilla, Ester; Jackson, Benjamin T; Wild, Sophia A; Kovacevic, Tatjana; Stork, Eva Maria; Zhou, Meng; Erard, Nicolas; Lee, Emily; Kelley, David R; Roth, Mareike; Barbosa, Inês AM; Zuber, Johannes; Rinn, John L

2017-01-01

A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting. PMID:28875933

lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.

PubMed

Delás, M Joaquina; Sabin, Leah R; Dolzhenko, Egor; Knott, Simon Rv; Munera Maravilla, Ester; Jackson, Benjamin T; Wild, Sophia A; Kovacevic, Tatjana; Stork, Eva Maria; Zhou, Meng; Erard, Nicolas; Lee, Emily; Kelley, David R; Roth, Mareike; Barbosa, Inês Am; Zuber, Johannes; Rinn, John L; Smith, Andrew D; Hannon, Gregory J

2017-09-06

A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting.

Evaluation of intrauterine adhesion treatment by laser hysteroscopy

NASA Astrophysics Data System (ADS)

Mutrynowski, Andrzej; Zabielska, Renata

1996-03-01

Hysteroscopy, which is a kind of endoscopy, makes it possible to evaluate macroscopically the cervical canal, uterine cavity, and the uterine opening of the oviducts. Laser hysteroscopy is used for removing septa and intrauterine adhesions, polyps, small submucosus myomas, and for endometrium ablation in abnormal metrorrhagias. The paper aims at the initial evaluation of laser hysteroscopy in removing intrauterine adhesions in the cases of 41 infertile women. Among all infertile patients 16 women (39%) conceived. Among others 1 woman (2.5%) did not want to conceive and 19 had other causes of infertility. Thirteen (93%) out of 14 patients with hypomenorrhea before surgery reported improvement of the menstruation cycle after the treatment. Five patients (12%) had adhesions for the second time. The patients had the second laser hysteroscopy. The control diagnostic hysteroscopy showed no adhesions in those cases.

Coxsackie Virus A16 Infection of Placenta with Massive Perivillous Fibrin Deposition Leading to Intrauterine Fetal Demise at 36 Weeks Gestation.

PubMed

Yu, Weiming; Tellier, Raymond; Wright, James R

2015-01-01

Massive perivillous fibrin deposition (MPFD) is an uncommon placental disorder, associated with significant fetal morbidity, mortality, and recurrence; its etiology is unknown. We describe a 31-year-old mother, diagnosed with Coxsackievirus infection and hand-foot-and-mouth disease at 35 weeks gestation. Ultrasound at 35 weeks revealed a normal fetus and placenta. One week later, the mother experienced decreased fetal movement and ultrasound demonstrated intrauterine demise. The autopsy showed mild, acute pericarditis and hypoxic-ischemic encephalopathy. Placenta examination showed MPFD involving 80% of the parenchyma. Molecular viral analysis and serotyping showed Coxsackie A16 virus. The mother had an uneventful pregnancy 15 months later. Coxsackievirus infections in pregnant mothers are often asymptomatic. Transplacental Coxsackievirus infection is very rare but is associated with spontaneous abortion, intrauterine demise, or serious neonatal morbidity. Mild, nonspecific histologic changes have been reported in the placenta. To our knowledge, this is the first report of MPFD associated with Coxsackievirus infection.

Differentiating cancerous from normal breast tissue by redox imaging

NASA Astrophysics Data System (ADS)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2015-02-01

Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (p<0.05) and the redox ratio Fp/(NADH+Fp) was about 27% higher in the cancerous tissues than in the normal ones (p<0.05). Our findings suggest that the redox state could differentiate between cancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

Limited Uptake of Planned Intrauterine Devices During the Postpartum Period.

PubMed

Salcedo, Jennifer; Moniaga, Natalie; Harken, Tabetha

2015-08-01

The primary objective of this study was to determine the percentage of women with a documented plan for postpartum intrauterine device (IUD) insertion who had a device inserted within 8 weeks of delivery. The secondary objective was to determine factors associated with successful initiation of postpartum IUDs as planned. We conducted a retrospective chart review of women who had at least one prenatal visit and delivered a viable pregnancy at our academic medical center. Methods of planned and established postpartum contraceptive methods were recorded, as well as demographic information and documented reasons for failure to initiate planned intrauterine contraception. A total of 110 women planned postpartum IUD placement. Of these women, 84 (76%) presented for at least one postpartum appointment. Only 22.6% (95% confidence interval 13.7-31.5) of those presenting for postpartum follow-up underwent IUD placement within 8 weeks of delivery. Women planning postpartum IUD insertion were just as likely as women with no planned postpartum contraceptive method to fail to establish contraception within 8 weeks (P = 0.55). Failure to establish planned postpartum intrauterine contraception occurs frequently, even in a setting with a high rate of postpartum follow-up.

Could linear MRI measurements of hippocampus differentiate normal brain aging in elderly persons from Alzheimer disease?

PubMed

Tarroun, Abdullah; Bonnefoy, Marc; Bouffard-Vercelli, Juliette; Gedeon, Claire; Vallee, Bernard; Cotton, François

2007-02-01

Although mild progressive specific structural brain changes are commonly associated with normal human aging, it is unclear whether automatic or manual measurements of these structures can differentiate normal brain aging in elderly persons from patients suffering from cognitive impairment. The objective of this study was primarily to define, with a standard high resolution MRI, the range of normal linear age-specific values for the hippocampal formation (HF), and secondarily to differentiate hippocampal atrophy in normal aging from that occurring in Alzheimer disease (AD). Two MRI-based linear measurements of the hippocampal formation at the level of the head and of the tail, standardized by the cranial dimensions, were obtained from coronal and sagittal T1-weighted MR images in 25 normal elderly subjects, and 26 patients with AD. In this study, dimensions of the HF have been standardized and they revealed normal distributions for each side and each sex: the width of the hippocampal head at the level of the amygdala was 16.42 +/- 1.9 mm, and its height 7.93 +/- 1.4 mm; the width of the tail at the level of the cerebral aqueduct was 8.54 +/- 1.2 mm, and the height 5.74 +/- 0.4 mm. There were no significant differences in standardized dimensions of the HF between sides, sexes, or in comparison to head dimensions in the two groups. In addition, the median inter-observer agreement index was 93%. In contrast, the dimensions of the hippocampal formation decreased gradually with increasing age, owing to physiological atrophy, but this atrophy is more significant in the group of AD.

A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement.

PubMed

Turok, David K; Eisenberg, David L; Teal, Stephanie B; Keder, Lisa M; Creinin, Mitchell D

2016-11-01

Misperceptions persist that intrauterine device placement is related to pelvic infections and Chlamydia and gonorrhea testing results are needed prior to placement. We sought to evaluate the relationship of Chlamydia and gonorrhea screening to pelvic infection for up to 2 years following placement of the levonorgestrel 52-mg intrauterine system. A total of 1751 nulliparous and multiparous females 16 to 45 years old enrolled in a multicenter trial designed to evaluate the efficacy and safety of a new levonorgestrel intrauterine system for up to 7 years. Participants had Chlamydia screening at study entry and yearly if they were age ≤25 years. Women also had baseline gonorrhea screening if testing had not been performed since starting their current sexual relationship. Those who changed sexual partners during the trial had repeated Chlamydia and gonorrhea testing. Intrauterine system insertion could occur on the same day as screening. Participants did not receive prophylactic antibiotics for intrauterine system placement. Investigators performed pelvic examinations after 12 and 24 months and when clinically indicated during visits at 3, 6, and 18 months after placement and unscheduled visits. Pelvic infection included any clinical diagnosis of pelvic inflammatory disease or endometritis. Most participants (n = 1364, 79.6%) did not have sexually transmitted infection test results available prior to intrauterine system placement. In all, 29 (1.7%) participants had positive baseline testing for a sexually transmitted infection (Chlamydia, n = 25; gonorrhea, n = 3; both, n = 1); 6 of these participants had known results (all with Chlamydia infection) prior to intrauterine system placement and received treatment before enrollment. The 23 participants whose results were not known at the time of intrauterine system placement received treatment without intrauterine system removal and none developed pelvic infection. The incidence of positive Chlamydia testing was

Maternal nutrition, intrauterine programming and consequential risks in the offspring.

PubMed

Yajnik, Chittaranjan S; Deshmukh, Urmila S

2008-09-01

It is traditionally believed that genetic susceptibility and adult faulty lifestyle lead to type 2 diabetes, a chronic non-communicable disease. The "Developmental Origins of Health and Disease" (DOHaD) model proposes that the susceptibility to type 2 diabetes originates in the intrauterine life by environmental fetal programming, further exaggerated by rapid childhood growth, i.e. a biphasic nutritional insult. Both fetal under nutrition (sometimes manifested as low birth weight) and over nutrition (the baby of a diabetic mother) increase the risk of future diabetes. The common characteristic of these two types of babies is their high adiposity. An imbalance in nutrition seems to play an important role, and micronutrients seem particularly important. Normal to high maternal folate status coupled with low vitamin B(12) status predicted higher adiposity and insulin resistance in Indian babies. Thus, 1-C (methyl) metabolism seems to play a key role in fetal programming. DOHaD represents a paradigm shift in the model for prevention of the chronic non-communicable diseases.

Curcumin and its synthetic analogue dimethoxycurcumin differentially modulates antioxidant status of normal human peripheral blood mononuclear cells.

PubMed

Simon, Emmanuel; Aswini, P; Sameer Kumar, V B; Mankadath, Gokuldas

2018-05-01

Curcumin is a polyphenol derived from the herb Curcuma longa, which has been extensively studied in terms of its antitumour, antioxidant, and chemopreventive activity as well as various other effects. In the present work we compared curcumin with its synthetic analogue dimethoxycurcumin (dimc) in terms of its antioxidant enzyme-modulating effects in human peripheral blood mononuclear cells (PBMC). We found that these compounds modulate antioxidant enzymes differentially. Both curcumin and dimethoxycurcumin effected a decrease in lipid peroxidation status in PBMC, however, curcumin had better activity in this regard. An increase in the activity of catalase was seen in the case of curcumin-treated PBMC, whereas dimc increased catalase activity significantly to almost twofold level. Real time-polymerase chain reaction (RT-PCR) analysis revealed significant up-regulation of catalase at mRNA level post treatment with curcumin as well as dimc, however, dimc had better activity in this regard. Glutathione reductase (GR) activity and reduced glutathione levels increased in the case of peripheral blood mononuclear cells (PBMC) treated with curcumin, however, the trend was reversed with dimethoxycurcumin where, both glutathione reductase activity and reduced glutathione levels were significantly reduced. RT-PCR analysis of glutathione reductase mRNA levels showed decrease in mRNA levels post treatment with dimethoxycurcumin (dimc) further corroborating GR enzyme assay results, however, we could not obtain significant result post curcumin treatment. NFkB reporter assay and western blot analysis of nuclear as well as cytosolic fractions of NFkB revealed that curcumin inhibits NFkB activation whereas inhibition was much less with dimc. It has been reported that curcumin and dimc exerts differential cytotoxicity in normal and tumour cells and the reason for this had been attributed to the differential uptake of these compounds by normal cells and tumour cells. Based on our

Genetic variant in CXCL13 gene is associated with susceptibility to intrauterine infection of hepatitis B virus

PubMed Central

Wan, Zhihua; Lin, Xiaofang; Li, Tongyang; Zhou, Aifen; Yang, Mei; Hu, Dan; Feng, Li; Peng, Songxu; Fan, Linlin; Tu, Si; Bin Zhang; Du, Yukai

2016-01-01

Intrauterine infection of hepatitis B virus (HBV), which accounts for the majority of mother-to-child transmission, is one of the main reasons for the failure of combined immunoprophylaxis against the transmission. Recent studies have identified that genetic background might influence the susceptibility to intrauterine infection of HBV. We conducted this study to investigate the associations between 10 genetic variants in 9 genes (SLC10A1, HLA-DP, HLA-C, CXCR5, CXCL13, TLR3, TLR4, TLR9 and UBE2L3) of mothers and their neonates and HBV intrauterine infection. A significantly decreased risk of HBV intrauterine transmission were found among mothers who carried the rs355687 CT genotypes in CXCL13 gene compared to those with CC genotypes (OR = 0.25, 95% CI, 0.08–0.82, P = 0.022); and a marginally significantly decreased risk was also observed under the dominant model (OR = 0.34, 95% CI, 0.11–1.01, P = 0.052). Besides, neonatal rs3130542 in HLA-C gene was found to be marginally significantly associated with decreased risk of HBV intrauterine infection under the additive model (OR = 0.55, 95% CI, 0.29–1.04, P = 0.064). However, we found no evidence of associations between the remaining 8 SNPs and risk of HBV intrauterine infection among mothers and their neonates. In conclusion, this study suggested that genetic variant in CXCL13 gene was associated with susceptibility to intrauterine infection of HBV. PMID:27212637

Delay Differential Equation Models of Normal and Diseased Electrocardiograms

NASA Astrophysics Data System (ADS)

Lainscsek, Claudia; Sejnowski, Terrence J.

Time series analysis with nonlinear delay differential equations (DDEs) is a powerful tool since it reveals spectral as well as nonlinear properties of the underlying dynamical system. Here global DDE models are used to analyze electrocardiography recordings (ECGs) in order to capture distinguishing features for different heart conditions such as normal heart beat, congestive heart failure, and atrial fibrillation. To capture distinguishing features of the different data types the number of terms and delays in the model as well as the order of nonlinearity of the DDE model have to be selected. The DDE structure selection is done in a supervised way by selecting the DDE that best separates different data types. We analyzed 24 h of data from 15 young healthy subjects in normal sinus rhythm (NSR) of 15 congestive heart failure (CHF) patients as well as of 15 subjects suffering from atrial fibrillation (AF) selected from the Physionet database. For the analysis presented here we used 5 min non-overlapping data windows on the raw data without any artifact removal. For classification performance we used the Cohen Kappa coefficient computed directly from the confusion matrix. The overall classification performance of the three groups was around 72-99 % on the 5 min windows for the different approaches. For 2 h data windows the classification for all three groups was above 95%.

[Premature fetal membrane rupture: report of a case of severe intrauterine fungal infection].

PubMed

Gauwerky, J; Schmidt, W; Kühn, H; Kubli, F

1983-03-01

A case of extremely rare intra-uterine candida infection is reported following premature rupture of the membranes. The diagnostic possibilities by transabdominal amniocentesis and determination of the causative organism in the amniotic fluid are presented. Even systemic antimykotic treatment is not capable of treating intra-uterine candidiasis sufficiently. This is proved among other parameters by the concentration of miconazol in the amniotic fluid and in the plasma of the newborn.

Differential gene expression analysis in glioblastoma cells and normal human brain cells based on GEO database.

PubMed

Wang, Anping; Zhang, Guibin

2017-11-01

The differentially expressed genes between glioblastoma (GBM) cells and normal human brain cells were investigated to performed pathway analysis and protein interaction network analysis for the differentially expressed genes. GSE12657 and GSE42656 gene chips, which contain gene expression profile of GBM were obtained from Gene Expression Omniub (GEO) database of National Center for Biotechnology Information (NCBI). The 'limma' data packet in 'R' software was used to analyze the differentially expressed genes in the two gene chips, and gene integration was performed using 'RobustRankAggreg' package. Finally, pheatmap software was used for heatmap analysis and Cytoscape, DAVID, STRING and KOBAS were used for protein-protein interaction, Gene Ontology (GO) and KEGG analyses. As results: i) 702 differentially expressed genes were identified in GSE12657, among those genes, 548 were significantly upregulated and 154 were significantly downregulated (p<0.01, fold-change >1), and 1,854 differentially expressed genes were identified in GSE42656, among the genes, 1,068 were significantly upregulated and 786 were significantly downregulated (p<0.01, fold-change >1). A total of 167 differentially expressed genes including 100 upregulated genes and 67 downregulated genes were identified after gene integration, and the genes showed significantly different expression levels in GBM compared with normal human brain cells (p<0.05). ii) Interactions between the protein products of 101 differentially expressed genes were identified using STRING and expression network was established. A key gene, called CALM3, was identified by Cytoscape software. iii) GO enrichment analysis showed that differentially expressed genes were mainly enriched in 'neurotransmitter:sodium symporter activity' and 'neurotransmitter transporter activity', which can affect the activity of neurotransmitter transportation. KEGG pathway analysis showed that the differentially expressed genes were mainly enriched in

Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

PubMed

Padilla, Nelly; Junqué, Carme; Figueras, Francesc; Sanz-Cortes, Magdalena; Bargalló, Núria; Arranz, Angela; Donaire, Antonio; Figueras, Josep; Gratacos, Eduard

2014-01-30

Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined. Copyright © 2013 Elsevier B.V. All rights reserved.

Language development in preschool children born after asymmetrical intrauterine growth retardation.

PubMed

Simić Klarić, Andrea; Kolundžić, Zdravko; Galić, Slavka; Mejaški Bošnjak, Vlatka

2012-03-01

After intrauterine growth retardation, many minor neurodevelopmental disorders may occur, especially in the motor skills domain, language and speech development, and cognitive functions. The assessment of language development and impact of postnatal head growth in preschool children born with asymmetrical intrauterine growth retardation. Examinees were born at term with birth weight below the 10th percentile for gestational age, parity and gender. Mean age at the time of study was six years and four months. The control group was matched according to chronological and gestational age, gender and maternal education with mean age six years and five months. There were 50 children with intrauterine growth retardation and 50 controls, 28 girls and 22 boys in each group. For the assessment of language development Reynell Developmental Language Scale, the Naming test and Mottier test were performed. There were statistically significant differences (p < 0.05) in language comprehension, total expressive language (vocabulary, structure, content), naming skills and non-words repetition. Statistically significant positive correlations were found between relative growth of the head [(Actual head circumference - head circumference at birth)/(Body weight - birth weight)] and language outcome. Children with neonatal complications had lower results (p < 0.05) in language comprehension and total expressive language. Intrauterine growth retardation has a negative impact on language development which is evident in preschool years. Slow postnatal head growth is correlated with poorer language outcome. Neonatal complications were negatively correlated with language comprehension and total expressive language. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Six-month expulsion of postplacental copper intrauterine devices placed after vaginal delivery.

PubMed

Gurney, Elizabeth P; Sonalkar, Sarita; Mcallister, Arden; Sammel, Mary D; Schreiber, Courtney A

2018-06-02

Immediate placement of an intrauterine device (IUD) after vaginal delivery is safe and convenient, but longitudinal data describing clinical outcomes have been limited. To determine the proportion of TCu380A (copper) IUDs devices expelled, partially expelled, malpositioned, and retained, as well as contraceptive use by 6 months postpartum. To determine risk factors for expulsion and partial expulsion. In this prospective, observational study, women who received a postplacental TCu380A IUD at vaginal delivery were enrolled postpartum. Participants returned for clinical follow-up at 6 weeks, and for a research visit with a pelvic exam and ultrasound at 6 months. We recorded IUD outcomes and 6-month contraceptive use. Partial expulsion was defined as an IUD protruding from the external cervical os, or a transvaginal ultrasound showing the distal end of the IUD below the internal os of the cervix. Multinomial logistic regression models identified risk factors associated with expulsion and partial expulsion by 6 months. The area under the receiver-operating characteristics (ROC) curve was used to assess the ability of a string check to predict the correct placement of a postplacental IUD. The primary outcome was the proportion of IUDs expelled at 6 months. We enrolled 200 women. Of 162 participants with follow-up data at 6 months, 13 (8.0%, 95% CI 4.7%-13.4%), experienced complete expulsion and 26 (16.0%, 95% CI 11.1%-22.6%) partial expulsion (see Figure 1). Of 25 malpositioned IUDs (15.4%, 95% CI 10.2%-21.9%), 14 were not at the fundus (8.6%, 95% CI 5.2%-14.1%) and 11 were rotated within the uterus (6.8%, 95% CI 3.8%-11.9%). Multinomial logistic regression modeling indicated that higher parity (OR 2.05; 95% CI 1.21-3.50, p=0.008) was associated with expulsion. Provider specialty (Obstetrics vs. Family Medicine; OR 5.31, 95% CI 1.20-23.59; p=0.03) and gestational weight gain (normal vs. excess; OR 9.12, 95% CI 1.90-43.82; p=0.004) were associated with partial expulsion

Non-contraceptive benefits of hormonal and intrauterine reversible contraceptive methods.

PubMed

Bahamondes, Luis; Valeria Bahamondes, M; Shulman, Lee P

2015-01-01

Most contraceptive methods present benefits beyond contraception; however, despite a large body of evidence, many healthcare professionals (HCPs), users and potential users are unaware of those benefits. This review evaluates the evidence for non-contraceptive benefits of hormonal and non-hormonal contraceptive methods. We searched the medical publications in PubMed, POPLINE, CENTRAL, EMBASE and LILACS for relevant articles, on non-contraceptive benefits of the use of hormonal and intrauterine reversible contraceptive methods, which were published in English between 1980 and July 2014. Articles were identified using the following search terms: 'contraceptive methods', 'benefits', 'cancer', 'anaemia', 'heavy menstrual bleeding (HMB)', 'endometrial hyperplasia', 'endometriosis' and 'leiomyoma'. We identified, through the literature search, evidence that some combined oral contraceptives have benefits in controlling HMB and anaemia, reducing the rate of endometrial, ovarian and colorectal cancer and ectopic pregnancy as well as alleviating symptoms of premenstrual dysphoric disorder. Furthermore, the use of the levonorgestrel-releasing intrauterine system also controls HMB and anaemia and endometrial hyperplasia and cancer, reduces rates of endometrial polyps in users of tamoxifen and alleviates pain associated with endometriosis and adenomyosis. Depot medroxyprogesterone acetate controls crises of pain associated with sickle cell disease and endometriosis. Users of the etonogestrel-releasing contraceptive implant have the benefits of a reduction of pain associated with endometriosis, and users of the copper intrauterine device have reduced rates of endometrial and cervical cancer. Despite the high contraceptive effectiveness of many hormonal and intrauterine reversible contraceptive methods, many HCPs, users and potential users are concerned mainly about side effects and safety of both hormonal and non-hormonal contraceptive methods, and there is scarce information

Intrauterine device insertion in the postpartum period: a systematic review.

PubMed

Sonalkar, Sarita; Kapp, Nathalie

2015-02-01

Given new research on postpartum placement of levonorgestrel and copper intrauterine devices (IUDs), our objective was to update a prior systematic review of the safety and expulsion rates of postpartum IUDs. We searched MEDLINE, CENTRAL, LILACS, POPLINE, Web of Science, and ClinicalTrials.gov databases for articles between the database inception until July 2013. We included studies that compared IUD insertion time intervals and routes during the postpartum period. We used standard abstract forms and the United States Preventive Services Task Force grading system to summarise and assess the quality of the evidence. We included 18 articles. New evidence suggests that a levonorgestrel releasing-intrauterine system (LNG-IUS) insertion within 48 hours of delivery is safe. Postplacental insertion and insertion between 10 minutes and 48 hours after delivery result in higher expulsion rates than insertion 4 to 6 weeks postpartum, or non-postpartum insertion. Insertion at the time of caesarean section is associated with lower expulsion rates than postplacental insertion at the time of vaginal delivery. This review supports the evidence that insertion of an intrauterine contraceptive within the first 48 hours of vaginal or caesarean delivery is safe. Expulsion rates should be further studied in larger randomised controlled trials.

Comparison of placebo and intrauterine lidocaine with/or without rectal diclofenac sodium suppositories used in office endometrial biopsy.

PubMed

Kaya, Cengiz; Sener, Elif Bengi; Koksal, Ersin; Ustun, Yasemin Burcu; Celik, Handan; Sahinoglu, Ali Haydar

2015-01-01

To compare the effects of intrauterine lidocaine, intrauterine lidocaine plus rectal diclofenac, and a placebo on analgesia and to determine the satisfaction of patients and surgeons in cases of endometrial biopsy. The double-blind, randomised, placebo-controlled study was conducted in the Department of Obstetrics and Gynaecology of the Ondokuz Mayis University, Samsun,Turkey, from April 2013 to January 2014, and comprised patients scheduled for in-office endometrial biopsy.They were divided into three groups: Group P, 5ml of 0.9% saline intrauterine; Group L, 5ml of 2% lidocaine intrauterine; and Group LD, 5ml of 2% lidocaine intrauterine ± 10min before the procedure plus 50mg of rectal diclofenac sodium. Haemodynamic changes and visual analogue scale scores were recorded during the preoperative period, when the cervix was grasped with a tenaculum, immediately after intrauterine instillation, during uterine curettage and at postoperative 10 min. The patient and the surgeon were questioned about their satisfaction 15 min after the procedure. SPSS 21 was used for statistical analysis. The 90 patients in the study were divided into three equal groups of 30(33.33%) each. There were no statistically significant inter-group differences in age, bodyweight, parity, number of postmenopausal patients, haemodynamic parameters and American Society of Anesthesiologists scores (p>0.05 in all categories). In Group P, the visual analogue scale score estimated when the cervix was grasped with the tenaculum was lower when compared with Group L and Group LD (p=0.029 and p=0.007, respectively). At other measurement time points, the scores did not differ between the groups. The groups did not differ with respect to patient and surgeon satisfaction and complication rates (p>0.05). Intrauterine lidocaine or intrauterine lidocaine plus rectal diclofenac application had no effect on visual analogue scale scores, patient satisfaction and vasovagal reaction.

The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells

PubMed Central

Guthrie, Katherine A.; Cummings, Carrie L.; Sabo, Kathleen; Wood, Brent L.; Gooley, Ted; Yang, Taimei; Epping, Mirjam T.; Shou, Yaping; Pogosova-Agadjanyan, Era; Ladne, Paula; Stirewalt, Derek L.; Abkowitz, Janis L.; Radich, Jerald P.

2009-01-01

The preferentially expressed antigen in melanoma (PRAME) is expressed in several hematologic malignancies, but either is not expressed or is expressed at only low levels in normal hematopoietic cells, making it a target for cancer therapy. PRAME is a tumor-associated antigen and has been described as a corepressor of retinoic acid signaling in solid tumor cells, but its function in hematopoietic cells is unknown. PRAME mRNA expression increased with chronic myeloid leukemia (CML) disease progression and its detection in late chronic-phase CML patients before tyrosine kinase inhibitor therapy was associated with poorer therapeutic responses and ABL tyrosine kinase domain point mutations. In leukemia cell lines, PRAME protein expression inhibited granulocytic differentiation only in cell lines that differentiate along this lineage after all-trans retinoic acid (ATRA) exposure. Forced PRAME expression in normal hematopoietic progenitors, however, inhibited myeloid differentiation both in the presence and absence of ATRA, and this phenotype was reversed when PRAME was silenced in primary CML progenitors. These observations suggest that PRAME inhibits myeloid differentiation in certain myeloid leukemias, and that its function in these cells is lineage and phenotype dependent. Lastly, these observations suggest that PRAME is a target for both prognostic and therapeutic applications. PMID:19625708

Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction--a pilot study.

PubMed

Caramelli, Elisabetta; Rizzo, Nicola; Concu, Manuela; Simonazzi, Giuliana; Carinci, Paolo; Bondavalli, Corrado; Bovicelli, Luciano; Farina, Antonio

2003-05-01

To evaluate if an increased amount of fetal DNA concentration can be found in women screened positive for intrauterine growth restriction because of abnormal uterine artery Doppler waveforms. We enrolled eight pregnant women (each bearing a male fetus), with the evidence of abnormal uterine artery Doppler waveforms, and 16 control patients for a case-control study matched for gestational age (1 : 2). Uterine artery Doppler was carried out at 20 to 35 weeks' gestation (median 29). The mean uterine artery resistance index (RI) was subsequently calculated, and a value >0.6 was considered positive for the clinical features of pre-eclampsia. The SRY locus was used to determine the amount of male fetal DNA in the maternal plasma at the time of Doppler analysis. Two controls (normal Doppler) were excluded from the final analysis because they had a pre-term delivery. One case (abnormal Doppler) had evidence of intrauterine growth restriction at the time of enrolment. In four out of eight cases (abnormal Doppler), intrauterine growth restriction was subsequently observed. Multiples of median (MoM) conversion of the fetal DNA values showed an increase of 1.81 times in the cases when compared to the controls. An increase of 2.16 times was instead observed for the cases with a growth-restricted fetus (5 cases out of 8) in comparison with the controls (14 cases). In subjects positive to uterine artery Doppler velocimetry analysis (Doppler analysis for pre-eclampsia screening), the fetal DNA concentration is higher than expected, in the absence of any other clinical feature. Since the increase in fetal DNA seems to be related to the presence or to the future development of intrauterine growth restriction, this paper suggests a possible integration between ultrasound and molecular markers for predicting the disease in some cases. Copyright 2003 John Wiley & Sons, Ltd.

Unprotected intercourse in the 2 weeks prior to requesting emergency intrauterine contraception.

PubMed

Sanders, Jessica N; Howell, Laura; Saltzman, Hanna M; Schwarz, E Bimla; Thompson, Ivana S; Turok, David K

2016-11-01

Previous emergency contraception studies have excluded women who report >1 episode of unprotected or underprotected intercourse. Thus, clinical recommendations are based on exposure to a single episode of underprotected intercourse. We sought to assess the prevalence and timing of underprotected intercourse episodes among women requesting emergency contraception and to examine the probability of pregnancy following an emergency contraception regimen including placement of either a copper intrauterine device or a levonorgestrel intrauterine device with simultaneous administration of an oral levonorgestrel pill in women reporting multiple underprotected intercourse episodes, including episodes beyond the Food and Drug Administration-approved emergency contraception time frame (6-14 days). Women seeking emergency contraception who had a negative pregnancy test and desired either a copper intrauterine device or levonorgestrel emergency contraception regimen enrolled in this prospective observational study. At enrollment, participants reported the number and timing of underprotected intercourse episodes in the previous 14 days. Two weeks later, participants reported the results of a self-administered home pregnancy test. Of the 176 women who presented for emergency contraception and received a same-day intrauterine device, 43% (n = 76) reported multiple underprotected intercourse episodes in the 14 days prior to presenting for emergency contraception. Women with multiple underprotected intercourse episodes reported a median of 3 events (range 2-20). Two-week pregnancy data were available for 172 (98%) participants. Only 1 participant had a positive pregnancy test. Pregnancy occurred in 0 of 97 (0%; 95% confidence interval, 0-3.7%) women with a single underprotected intercourse episode and 1 of 75 (1.3%; 95% confidence interval, 0-7.2%) women reporting multiple underprotected intercourse episodes; this includes 1 of 40 (2.5%; 95% confidence interval, 0-13.2%) women

Normalization of similarity-based individual brain networks from gray matter MRI and its association with neurodevelopment in infants with intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Figueras, Francesc; Bargallo, Nuria; Eixarch, Elisenda; Gratacos, Eduard

2013-12-01

Obtaining individual biomarkers for the prediction of altered neurological outcome is a challenge of modern medicine and neuroscience. Connectomics based on magnetic resonance imaging (MRI) stands as a good candidate to exhaustively extract information from MRI by integrating the information obtained in a few network features that can be used as individual biomarkers of neurological outcome. However, this approach typically requires the use of diffusion and/or functional MRI to extract individual brain networks, which require high acquisition times and present an extreme sensitivity to motion artifacts, critical problems when scanning fetuses and infants. Extraction of individual networks based on morphological similarity from gray matter is a new approach that benefits from the power of graph theory analysis to describe gray matter morphology as a large-scale morphological network from a typical clinical anatomic acquisition such as T1-weighted MRI. In the present paper we propose a methodology to normalize these large-scale morphological networks to a brain network with standardized size based on a parcellation scheme. The proposed methodology was applied to reconstruct individual brain networks of 63 one-year-old infants, 41 infants with intrauterine growth restriction (IUGR) and 22 controls, showing altered network features in the IUGR group, and their association with neurodevelopmental outcome at two years of age by means of ordinal regression analysis of the network features obtained with Bayley Scale for Infant and Toddler Development, third edition. Although it must be more widely assessed, this methodology stands as a good candidate for the development of biomarkers for altered neurodevelopment in the pediatric population. © 2013 Elsevier Inc. All rights reserved.

Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

PubMed

Spiroski, A-M; Oliver, M H; Harding, J E; Bloomfield, F H

2016-01-01

Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

Haploid parthenotes express differential response to in vitro exposure of ammonia compared to normally fertilized embryos.

PubMed

Nair, Ramya; Mutalik, Srinivas; Dasappa, Jagadeesh Prasad; Kalthur, Guruprasad; Adiga, Satish Kumar

2017-04-22

In the present study, we assessed whether absence of paternal genome imparts any differential response in embryos to chemical stress such as ammonia. Parthenogenesis was induced in MII stage oocytes using 10 mM SrCl 2 in M16 medium. Parthenotes and normally fertilized embryos at 2 cell stage were exposed to different concentrations of ammonia and cultured till blastocyst. Exposure of ammonia to normally fertilized embryos resulted in significant decrease in the developmental potential (p < 0.0001) and blastocyst quality (p < 0.001). Whereas, in parthenotes, even though lower concentrations of ammonia did not have any effect, at 200 μM concentration the blastocyst rate was two times higher than control. The baseline apoptotic index was higher in parthenotes compared to normally fertilized embryos, which further increased after ammonium exposure (p < 0.001). Unlike in normally fertilized embryos ammonia exposure altered the mitochondrial distribution pattern and lead to increased expression of Oct4, Nanog and Na + /K + ion exchange channel, while the cytochrome C expression was downregulated. This indicates that haploidy and/or absence of paternal factors in the embryo results in differential tolerance to stress induced by ammonia. Copyright © 2017 Elsevier Inc. All rights reserved.

Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

PubMed

Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

2006-12-01

Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P < .01). In addition, alpha

Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles.

PubMed

Souren, Nicole Y P; Lutsik, Pavlo; Gasparoni, Gilles; Tierling, Sascha; Gries, Jasmin; Riemenschneider, Matthias; Fryns, Jean-Pierre; Derom, Catherine; Zeegers, Maurice P; Walter, Jörn

2013-05-26

Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes. Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences. Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies.

Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR).

PubMed

Gonzalez-Rodriguez, Pablo; Cantu, Jessica; O'Neil, Derek; Seferovic, Maxim D; Goodspeed, Danielle M; Suter, Melissa A; Aagaard, Kjersti M

2016-05-01

The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. Growth-restricted F2 on control diet demonstrated significant down-regulation in H19

Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth.

PubMed

Hinkle, Stefanie N; Johns, Alicia M; Albert, Paul S; Kim, Sungduk; Grantz, Katherine L

2015-07-01

Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at 17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed models. Second, the association between maternal weight changes (per 5 kg) and corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. From 0 to 17 weeks, changes in maternal weight were most strongly associated with changes in BPD [β=0.51 per 5 kg (95%CI 0.26, 0.76)] and FL [β=0.46 per 5 kg (95%CI 0.26, 0.65)]. From 17 to 28 weeks, AC [β=2.92 per 5 kg (95%CI 1.62, 4.22)] and EFW [β=58.7 per 5 kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29 kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67 kg

Long QT Syndrome–Associated Mutations in Intrauterine Fetal Death

PubMed Central

Crotti, Lia; Tester, David J.; White, Wendy M.; Bartos, Daniel C.; Insolia, Roberto; Besana, Alessandra; Kunic, Jennifer D.; Will, Melissa L.; Velasco, Ellyn J.; Bair, Jennifer J.; Ghidoni, Alice; Cetin, Irene; Van Dyke, Daniel L.; Wick, Myra J.; Brost, Brian; Delisle, Brian P.; Facchinetti, Fabio; George, Alfred L.; Schwartz, Peter J.; Ackerman, Michael J.

2013-01-01

Importance Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. Objective To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. Design, Setting, and Patients In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. Main Outcomes and Measures Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. Results The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2[1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation

Intrauterine contraception.

PubMed

Reinprayoon, D

1992-08-01

Currently 85 million women use an intrauterine device (IUD), making it the most widely used, reliable, reversible contraceptive method worldwide. Although the exact mechanisms by which copper-bearing IUDs produce contraceptive action are not completely defined, recent evidence indicates that they act primarily to prevent sperm from fertilizing ova. The future of the IUD is brighter than it has been for the past 20 years. The latest generation of IUDs, such as the TCu 380A (Paragard, GynoPharma, Somerville, NJ), are safer and more effective than ever. In World Health Organization large, multicenter trials, pregnancy rates for the TCu 380A are 1.0, 1.4, 1.6, and 1.8 at 3, 5, 7, and 9 years of use, respectively. The ectopic pregnancy rates and removal for pelvic inflammatory disease are very low. The device may soon be the major IUD available in most countries. The acceptability of IUD use can be increased by good clinical management, sympathetic counseling, careful client selection, proper device selection, careful insertion, timing of insertion, and regular follow-up with quick access to medical care.

Synovial fluid progenitors expressing CD90+ from normal but not osteoarthritic joints undergo chondrogenic differentiation without micro-mass culture.

PubMed

Krawetz, Roman J; Wu, Yiru Elizabeth; Martin, Liam; Rattner, Jerome B; Matyas, John R; Hart, David A

2012-01-01

Mesenchymal progenitor cells (MPCs) can differentiate into osteoblasts, adipocytes, and chondrocytes, and are in part responsible for maintaining tissue integrity. Recently, a progenitor cell population has been found within the synovial fluid that shares many similarities with bone marrow MPCs. These synovial fluid MPCs (sfMPCs) share the ability to differentiate into bone and fat, with a bias for cartilage differentiation. In this study, sfMPCs were isolated from human and canine synovial fluid collected from normal individuals and those with osteoarthritis (human: clinician-diagnosed, canine: experimental) to compare the differentiation potential of CD90+ vs. CD90- sfMPCs, and to determine if CD90 (Thy-1) is a predictive marker of synovial fluid progenitors with chondrogenic capacity in vitro. sfMPCs were derived from synovial fluid from normal and OA knee joints. These cells were induced to differentiate into chondrocytes and analyzed using quantitative PCR, immunofluorescence, and electron microscopy. The CD90+ subpopulation of sfMPCs had increased chondrogenic potential compared to the CD90- population. Furthermore, sfMPCs derived from healthy joints did not require a micro-mass step for efficient chondrogenesis. Whereas sfMPCs from OA synovial fluid retain the ability to undergo chondrogenic differentiation, they require micro-mass culture conditions. Overall, this study has demonstrated an increased chondrogenic potential within the CD90+ fraction of human and canine sfMPCs and that this population of cells derived from healthy normal joints do not require a micro-mass step for efficient chondrogenesis, while sfMPCs obtained from OA knee joints do not differentiate efficiently into chondrocytes without the micro-mass procedure. These results reveal a fundamental shift in the chondrogenic ability of cells isolated from arthritic joint fluids, and we speculate that the mechanism behind this change of cell behavior is exposure to the altered milieu of the OA

Adipocyte differentiation influences the proliferation and migration of normal and tumoral breast epithelial cells.

PubMed

Creydt, Virginia Pistone; Sacca, Paula Alejandra; Tesone, Amelia Julieta; Vidal, Luciano; Calvo, Juan Carlos

2010-01-01

Stromal tissue regulates the development and differentiation of breast epithelial cells, with adipocytes being the main stromal cell type. The aim of the present study was to evaluate the effect of adipocyte differentiation on proliferation and migration, as well as to assess the activity of heparanase and metalloproteinase-9 (MMP-9), in normal (NMuMG) and tumoral (LM3) murine breast epithelial cells. NMuMG and LM3 cells were grown on irradiated 3T3-L1 cells (stromal support, SS) at various degrees of differentiation [preadipocytes (preA), poorly differentiated adipocytes (pDA) and mature adipocytes (MA)] and/or were incubated in the presence of conditioned medium (CM) derived from each of these three types of differentiated cells. Cells grown on a plastic support or in fresh medium served as the controls. Cell proliferation was measured with a commercial colorimetric kit, and the motility of the epithelial cells was evaluated by means of a wound-healing assay. Heparanase activity was assessed by quantifying heparin degradation, and the expression of MMP-9 was determined using Western blotting. The results indicate that cell proliferation was increased after 24 and 48 h in the NMuMG and LM3 cells grown on preA, pDA and MA SS. In the NMuMG cells cultured on SS in the presence of all three types of CM, proliferation was enhanced. LM3 cell migration was increased in the presence of all three types of CM and in cells grown on preA SS. Heparanase activity was increased in the NMuMG cells incubated with all three types of CM, and in the LM3 cells incubated with the CM from pDA and MA. Both the NMuMG and LM3 cell lines presented basal expression of MMP-9; however, a significant increase in MMP-9 expression was observed in the LM3 cells incubated with each of the three types of CM. In conclusion, adipocyte differentiation influences normal and tumoral breast epithelial cell proliferation and migration. Heparanase and MMP-9 appear to be involved in this regulation. The

Metabolomic analysis of the longissimus from underperforming piglets suggests impaired carbohydrate metabolism, increased lipid utilization and higher protein breakdown in comparison to piglets with normal preweaning growth

USDA-ARS?s Scientific Manuscript database

The present study was designed to determine if normal birth weight pigs that grow poorly during the pre-weaning period have altered skeletal muscle metabolism, as previously reported for intrauterine growth retarded pigs relative to littermates with normal growth rates. Eight pairs of average birth...

EFFECT OF INTRAUTERINE PCB EXPOSURE ON VISUAL RECOGNITION MEMORY

EPA Science Inventory

Adverse neonatal outcomes have been associated with intrauterine exposure to polychlorinated biphenyls (PCBs). In a follow-up study of exposed and nonexposed infants, 123 infants tested at birth were administered Fagan's test of visual recognition memory at 7 months. 2 measures o...

Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

PubMed

Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

2014-09-10

Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

Evaluation of quality of life and sexual functioning of women using levonorgestrel-releasing intrauterine contraceptive system--Mirena.

PubMed

Skrzypulec, Violetta; Drosdzol, Agnieszka

2008-12-01

The advantages ensuing from the high contraceptive efficacy, positive effect on the parameters of the menstrual cycle as well as other values of the levonorgestrel-releasing intrauterine system may play an important role in women's sexual life. The aim of the study was to evaluate the effect of the levonorgestrel-releasing intrauterine system on the quality of life and sexual functioning of women. The research encompassed 200 women aged between 30 and 45. 52 women using the levonorgestrel-releasing intrauterine system were qualified to the study as the research group (Mirena Group). The control groups consisted of 48 women using a different type of intrauterine device (Control Group I--Other IUD) and 50 women using no contraception (Control Group II). A specific questionnaire with a general part concerning socio-demographic conditions, a part dealing with contraception and Polish version of self-evaluation inventories: Short Form-36 Health Survey, Female Sexual Function Index and Mell-Krat Scale was used as a research tool. Quality of life parameters for women using the Mirena system were higher than for the control groups, especially in the aspect of general health, energy/fatigue and emotional well-being. A significant beneficial effect of the levonorgestrel-releasing intrauterine system on sexual functioning (sexual desire and arousal) was also revealed in the study. Sexual dysfunctions were diagnosed in 20.8% of Other IUD, 34.7% of Control Group II and 9.6% of Mirena Group. Levonorgestrel-releasing intrauterine system increases female quality of life and sexual functioning parameters.

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.

PubMed

Joó, József Gábor; Rigó, János; Börzsönyi, Balázs; Demendi, Csaba; Kornya, László

2017-06-01

We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2 α : 0.92; p < 0.06). Within the IUGR group, no fetal gender-dependent differences were seen in placental PIGF gene expression (Ln2 α : 0.72; p = 0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2 α : -1.49; p < 0.03). We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

Two-year continuation of intrauterine devices and contraceptive implants in a mixed-payer setting: a retrospective review.

PubMed

Sanders, Jessica N; Turok, David K; Gawron, Lori M; Law, Amy; Wen, Lonnie; Lynen, Richard

2017-06-01

As the popularity of long-acting reversible contraception increases, so does the need for accurate data on method continuation in diverse clinical settings. We determined 2-year continuation rates for the levonorgestrel 52-mg intrauterine device, the copper T380A intrauterine device, and the 68-mg etonogestrel contraceptive implant in an academic healthcare system with mixed-payer reimbursement. The purpose of this study was to examine the proportion and characteristics of women who continue intrauterine device and implant use to 2 years and to relate continuation to device type when controlling for patient characteristics. This retrospective chart review assessed University of Utah Healthcare System patients who had an intrauterine device or contraceptive implant inserted between January 1, 2004, and December 31, 2012. We identified users and dates of insertions and removals by querying billing, medication, and procedural data in the Electronic Data Warehouse. Multivariable Poisson regression was conducted to estimate incidence risk ratios and to relate the probability of 2-year continuous use to device type. Data on 8603 device insertions were obtained with the following distribution: levonorgestrel 52-mg intrauterine devices (6459; 75.1%), copper T380A intrauterine devices (1136; 13.2%), and 68-mg etonogestrel implant (1008; 11.7%). Two-year continuation rates were 77.8%, 73.1%, and 75.9%, respectively. There was no statistical difference in 2-year continuation between levonorgestrel 52-mg intrauterine device users (adjusted risk ratio, 1.1; 95% confidence interval, 1.0-1.1) and 68-mg etonogestrel implant users (adjusted risk ratio, 1.1; 95% confidence interval, 1.0-1.1) compared with copper device users, after we controlled for age, Hispanic ethnicity, payer type, and year of insertion. Older-age, self-pay, or public payer insurance (reference commercial payer) and Hispanic ethnicity were associated with 2-year continuation. Three-quarters of women with an

Effects of social stress and intrauterine position on sexual phenotype in wild-type house mice (Mus musculus)

Treesearch

William J. Zielinski; John G. Vandenbergh; Monica M. Montano

1991-01-01

Wild-type house mice were used to test the effect of intrauterine position on anogenital distance (AGD) and to verify whether crowding stress would masculinize female pups, developing at all intrauterine positions, as has been demonstrated in CF-1 mice stressed by restraint, heat, and...

What is the normal response to structural differentiation within the slump and straight leg raise tests?

PubMed

Herrington, Lee; Bendix, Katie; Cornwell, Catherine; Fielden, Nicola; Hankey, Karen

2008-08-01

The purpose of the study was to assess the effect of structural differentiation or sensitising manoeuvres on responses of normal subjects to standard neurodynamic tests of straight leg raise (SLR) and slump test. Eighty-eight (39 males and 49 females) asymptomatic subjects were examined (aged 18-39 mean age 21.9+/-4.1 years). Knee flexion angle was measured using a goniometer during the slump test in two conditions cervical flexion and extension. Hip flexion angle was measured using a goniometer during SLR test in two conditions; ankle dorsi-flexion and neutral. The change in knee flexion, following addition of the structural differentiating manoeuvre to the slump test, was a significant increase in knee flexion angle for both males (change in knee angle; 6.6+/-4.7 degrees /18.7+/-17.5%, p<0.01) and females (change in knee angle 5.4+/-5.8 degrees /17.6+/-23.7%, p<0.01), though showed no difference between sides (p>0.05). During the SLR test, a significant reduction in hip flexion occurred following structural differentiation for both groups (change in hip angle; males = 9.5+/-8.3 degrees /21.5+/-18.8%, p<0.01; females = 15.2+/-9.5 degrees /25.9+/-13.9%, p<0.01), though showed no difference between sides (p>0.05). Structural differentiating manoeuvres have a significant effect on test response in terms of range of movement even in normal asymptomatic individuals. These responses should be taken into account during the assessment clinical reasoning process.

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

PubMed Central

Entringer, Sonja; Buss, Claudia; Swanson, James M.; Cooper, Dan M.; Wing, Deborah A.; Waffarn, Feizal; Wadhwa, Pathik D.

2012-01-01

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice. PMID:22655178

Training contraceptive providers to offer intrauterine devices and implants in contraceptive care: a cluster randomized trial.

PubMed

Thompson, Kirsten M J; Rocca, Corinne H; Stern, Lisa; Morfesis, Johanna; Goodman, Suzan; Steinauer, Jody; Harper, Cynthia C

2018-06-01

US unintended pregnancy rates remain high, and contraceptive providers are not universally trained to offer intrauterine devices and implants to women who wish to use these methods. We sought to measure the impact of a provider training intervention on integration of intrauterine devices and implants into contraceptive care. We measured the impact of a continuing medical education-accredited provider training intervention on provider attitudes, knowledge, and practices in a cluster randomized trial in 40 US health centers from 2011 through 2013. Twenty clinics were randomly assigned to the intervention arm; 20 offered routine care. Clinic staff participated in baseline and 1-year surveys assessing intrauterine device and implant knowledge, attitudes, and practices. We used a difference-in-differences approach to compare changes that occurred in the intervention sites to changes in the control sites 1 year later. Prespecified outcome measures included: knowledge of patient eligibility for intrauterine devices and implants; attitudes about method safety; and counseling practices. We used multivariable regression with generalized estimating equations to account for clustering by clinic to examine intervention effects on provider outcomes 1 year later. Overall, we surveyed 576 clinic staff (314 intervention, 262 control) at baseline and/or 1-year follow-up. The change in proportion of providers who believed that the intrauterine device was safe was greater in intervention (60% at baseline to 76% at follow-up) than control sites (66% at both times) (adjusted odds ratio, 2.48; 95% confidence interval, 1.13-5.4). Likewise, for the implant, the proportion increased from 57-77% in intervention, compared to 61-65% in control sites (adjusted odds ratio, 2.57; 95% confidence interval, 1.44-4.59). The proportion of providers who believed they were experienced to counsel on intrauterine devices also increased in intervention (53-67%) and remained the same in control sites (60

Cost-effectiveness analysis of a low-dose contraceptive levonorgestrel intrauterine system in Sweden.

PubMed

Henry, Nathaniel; Hawes, Charlie; Lowin, Julia; Lekander, Ingrid; Filonenko, Anna; Kallner, Helena K

2015-08-01

To evaluate the cost-effectiveness of a novel intrauterine system, levonorgestrel intrauterine system 13.5 mg vs. oral contraception, in women at risk of unintended pregnancy. Cost-effectiveness model using efficacy and discontinuation data from published articles. Societal perspective including direct and indirect costs. Women at risk of unintended pregnancy using reversible contraception. An economic analysis was conducted by modeling the different health states of women using contraception over a 3-year period. Typical use efficacy rates from published articles were used to determine unintended pregnancy events. Discontinuation rates were used to account for method switching. Cost-effectiveness was evaluated in terms of the incremental cost per unintended pregnancy avoided. In addition, the incremental cost per quality-adjusted life-year was calculated. Levonorgestrel intrauterine system 13.5 mg generated costs savings of € 311,000 in a cohort of 1000 women aged 15-44 years. In addition, there were fewer unintended pregnancies (55 vs. 294) compared with women using oral contraception. Levonorgestrel intrauterine system 13.5 mg is a cost-effective method when compared with oral contraception. A shift in contraceptive use from oral contraception to long-acting reversible contraception methods could result in fewer unintended pregnancies, quality-adjusted life-year gains, as well as cost savings. © 2015 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

The potential role of elastography in differentiating between endometrial polyps and submucosal fibroids: a preliminary study

PubMed Central

2015-01-01

Endometrial polyps and submucosal fibroids are common causes of abnormal uterine bleeding (AUB) and less commonly infertility. The prevalence of such intrauterine lesions increases with age during the reproductive years, and usually decreases after menopause. The first-line imaging examination in the diagnosis of endometrial polyps as well as submucosal fibroidsis ultrasound, but its accuracy is not obvious. Elastography is an ultrasound-based imaging modality that is used to assess the stiffness of examined tissues. Considering the fact that endometrial polyps derive from soft endometrial tissue and submucosal fibroids are made of hard muscle tissue, elastography seems a perfect tool to differentiate between such lesions. I present two groups of patients with AUB and intrauterine lesions suspected on ultrasound. In the first group of patients, elastography showed that the stiffness of the lesion was similar to the endometrium and softer than the myometrium. During hysteroscopies endometrial polyps were removed. In the second group of patients, elastography showed that the stiffness of the lesion was similar to the myometrium and harder than the endometrium. During hysteroscopies submucosal fibroids were removed. In both groups, the diagnosis was confirmed by the pathological examination in all cases. It was demonstrated that with the use of elastography it is possible to assess the stiffness of intrauterine lesions, which may be useful in differentiating between endometrial polyps and submucosal fibroids. PMID:26327901

The potential role of elastography in differentiating between endometrial polyps and submucosal fibroids: a preliminary study.

PubMed

Woźniak, Sławomir

2015-06-01

Endometrial polyps and submucosal fibroids are common causes of abnormal uterine bleeding (AUB) and less commonly infertility. The prevalence of such intrauterine lesions increases with age during the reproductive years, and usually decreases after menopause. The first-line imaging examination in the diagnosis of endometrial polyps as well as submucosal fibroidsis ultrasound, but its accuracy is not obvious. Elastography is an ultrasound-based imaging modality that is used to assess the stiffness of examined tissues. Considering the fact that endometrial polyps derive from soft endometrial tissue and submucosal fibroids are made of hard muscle tissue, elastography seems a perfect tool to differentiate between such lesions. I present two groups of patients with AUB and intrauterine lesions suspected on ultrasound. In the first group of patients, elastography showed that the stiffness of the lesion was similar to the endometrium and softer than the myometrium. During hysteroscopies endometrial polyps were removed. In the second group of patients, elastography showed that the stiffness of the lesion was similar to the myometrium and harder than the endometrium. During hysteroscopies submucosal fibroids were removed. In both groups, the diagnosis was confirmed by the pathological examination in all cases. It was demonstrated that with the use of elastography it is possible to assess the stiffness of intrauterine lesions, which may be useful in differentiating between endometrial polyps and submucosal fibroids.

Fetal tissue Doppler imaging in pregnancies complicated with preeclampsia with or without intrauterine growth restriction.

PubMed

Zhou, Qiongjie; Ren, Yunyun; Yan, Yingliu; Chu, Chen; Gui, Yonghao; Li, Xiaotian

2012-11-01

This study's aim was to evaluate the effect of preeclampsia and intrauterine growth restriction (IUGR) on fetal cardiac function, and the relationship of the latter with adverse pregnancy outcomes. We did a cross-sectional study of 132 women with uncomplicated singleton pregnancies, 34 with preeclampsia without IUGR, and 12 with preeclampsia and IUGR. Fetal cardiac structure and function were evaluated using fetal two-dimension ultrasound, pulsed wave Doppler and tissue Doppler imaging (TDI). Data were analyzed by t-tests, ANOVA, Chi-square tests, or Wilcoxon rank-sum test. Compared with the normal pregnancy group, mitral/tricuspid early systolic peak velocity of annulus/late diastolic peak velocity of annulus (Sa) and left ventricular (LV)/right ventricular (RV) early diastolic peak velocity at the annulus (Ea) in TDI decreased in preeclampsia with or without IUGR (P < 0.05). LV/RV Ea underwent a gestational decrease in preeclampsia with or without IUGR (P < 0.05). The changes in mitral/tricuspid Sa and LV Sa associated with preeclampsia were even more pronounced with preterm delivery at less than 34 gestational weeks and stillbirth (P < 0.05). Intrauterine growth restriction influences fetal cardiac function in the presence of preeclampsia, and TDI may be a sensitive and preferable method to detect such changes. Fetal LV/RV Ea is a potential marker for early fetal cardiac diastolic impairment, and mitral/tricuspid Sa and LV Sa may be predictors for adverse pregnancy outcomes. © 2012 John Wiley & Sons, Ltd.

Medium-chain TAG improve energy metabolism and mitochondrial biogenesis in the liver of intra-uterine growth-retarded and normal-birth-weight weanling piglets.

PubMed

Zhang, Hao; Li, Yue; Hou, Xiang; Zhang, Lili; Wang, Tian

2016-05-01

We previously reported that medium-chain TAG (MCT) could alleviate hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). There is a relationship between oxidative status and energy metabolism, a process involved in substrate availability and glucose flux. Therefore, the aim of this study was to investigate the effects of IUGR and MCT on hepatic energy metabolism and mitochondrial function in weanling piglets. Twenty-four IUGR piglets and twenty-four normal-birth-weight (NBW) piglets were fed a diet of either soyabean oil (SO) or MCT from 21 d of postnatal age to 49 d of postnatal age. Then, the piglets' biochemical parameters and gene expressions related to energy metabolism and mitochondrial function were determined (n 4). Compared with NBW, IUGR decreased the ATP contents and succinate oxidation rates in the liver of piglets, and reduced hepatic mitochondrial citrate synthase (CS) activity (P<0·05). IUGR piglets exhibited reductions in hepatic mitochondrial DNA (mtDNA) contents and gene expressions related to mitochondrial biogenesis compared with NBW piglets (P<0·05). The MCT diet increased plasma ghrelin concentration and hepatic CS and succinate dehydrogenase activities, but decreased hepatic pyruvate kinase activity compared with the SO diet (P<0·05). The MCT-fed piglets showed improved mtDNA contents and PPARγ coactivator-1α expression in the liver (P<0·05). The MCT diet alleviated decreased mRNA abundance of the hepatic PPARα induced by IUGR (P<0·05). It can therefore be postulated that MCT may have beneficial effects in improving energy metabolism and mitochondrial function in weanling piglets.

21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Intrauterine pressure monitor and accessories. 884.2700 Section 884.2700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... include the following accessories: signal analysis and display equipment, patient and equipment supports...

21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intrauterine pressure monitor and accessories. 884.2700 Section 884.2700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... include the following accessories: signal analysis and display equipment, patient and equipment supports...

21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intrauterine pressure monitor and accessories. 884.2700 Section 884.2700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... include the following accessories: signal analysis and display equipment, patient and equipment supports...

Hormonal and intrauterine methods for contraception for women aged 25 years and younger.

PubMed

Krashin, Jamie; Tang, Jennifer H; Mody, Sheila; Lopez, Laureen M

2015-08-17

Women between the ages of 15 and 24 years have high rates of unintended pregnancy; over half of women in this age group want to avoid pregnancy. However, women under age 25 years have higher typical contraceptive failure rates within the first 12 months of use than older women. High discontinuation rates may also be a problem in this population. Concern that adolescents and young women will not find hormonal or intrauterine contraceptives acceptable or effective might deter healthcare providers from recommending these contraceptive methods. To compare the contraceptive failure (pregnancy) rates and to examine the continuation rates for hormonal and intrauterine contraception among young women aged 25 years and younger. We searched until 4 August 2015 for randomized controlled trials (RCTs) that compared hormonal or intrauterine methods of contraception in women aged 25 years and younger. Computerized databases included the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS. We also searched for current trials via ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We considered RCTs in any language that reported the contraceptive failure rates for hormonal or intrauterine contraceptive methods, when compared with another contraceptive method, for women aged 25 years and younger. The other contraceptive method could have been another intrauterine contraceptive, another hormonal contraceptive or different dose of the same method, or a non-hormonal contraceptive. Treatment duration must have been at least three months. Eligible trials had to include the primary outcome of contraceptive failure rate (pregnancy). The secondary outcome was contraceptive continuation rate. One author conducted the primary data extraction and entered the information into Review Manager. Another author performed an independent data extraction and verified the initial entry. For dichotomous outcomes, we computed the

Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

PubMed Central

Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

2013-01-01

Abstract Objective: This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. Materials and methods: We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. Results: During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit – 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Conclusion: Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. PMID:24868262

Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

PubMed

Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

2013-01-01

This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit - 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease.

[Intrauterine growth restriction: endocrinological perspective. Update of the 2007 version (Arch Argent Pediatr 2007;105(1):71-73)].

PubMed

2017-06-01

Most children born with low weight or intrauterine growth restriction develop catch-up growth that allows them to reach a final height according to their genetic target height. However, in about 15% of children this growth is insufficient. In both, children who have adequate compensatory growth and therefore normal height and children who remain low in childhood, it is necessary to take into account that if puberty starts early, the final height could be compromised. Timely and appropriate intervention could improve it. Control of body weight is also important, as an excessive gain in childhood is associated with metabolic complications in adolescence and adult life. Sociedad Argentina de Pediatría.

Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

PubMed Central

2013-01-01

Background Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes. Results Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences. Conclusions Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. PMID:23706164

Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats.

PubMed

Liu, Xiaomei; Qi, Ying; Gao, Hong; Jiao, Yisheng; Gu, Hui; Miao, Jianing; Yuan, Zhengwei

2013-01-01

It is well recognized that intrauterine growth restriction leads to the development of insulin resistance and type 2 diabetes mellitus in adulthood. To investigate the mechanisms behind this "metabolic imprinting" phenomenon, we examined the impact of maternal undernutrition on insulin signaling pathway and the ATP sensitive potassium channel expression in the hypothalamus of intrauterine growth restriction fetus. Intrauterine growth restriction rat model was developed through maternal low protein diet. The expression and activated levels of insulin signaling molecules and K(ATP) protein in the hypothalami which were dissected at 20 days of gestation, were analyzed by western blot and real time PCR. The tyrosine phosphorylation levels of the insulin receptor substrate 2 and phosphatidylinositol 3'-kinase p85α in the hypothalami of intrauterine growth restriction fetus were markedly reduced. There was also a downregulation of the hypothalamic ATP sensitive potassium channel subunit, sulfonylurea receptor 1, which conveys the insulin signaling. Moreover, the abundances of gluconeogenesis enzymes were increased in the intrauterine growth restriction livers, though no correlation was observed between sulfonylurea receptor 1 and gluconeogenesis enzymes. Our data suggested that aberrant intrauterine milieu impaired insulin signaling in the hypothalamus, and these alterations early in life might contribute to the predisposition of the intrauterine growth restriction fetus toward the adult metabolic disorders.

Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

PubMed Central

Pfeifer, A M; Lechner, J F; Masui, T; Reddel, R R; Mark, G E; Harris, C C

1989-01-01

The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells. PMID:2538323

[Twin pregnancy with intrauterine death of one fetus: maternal and neonatal outcome of surviving fetus].

PubMed

Fernández-Miranda, María de la Calle; Cruceyra Bertriu, Mireia; Rodríuez-González, Roberto; Magdaleno-Dans, Fernando; Omeñaca Teres, Félix; González González, Antonio

2012-04-01

happens in the womb when the death of one of the twins, it is necessary to consider the factors that influence the perinatal outcome of surviving fetus. To review the outcome of twin pregnancies complicated by single fetal intrauterine death and how it can increase morbidity to its co-twin and its mother. A retrospective analysis of the fifty one twin pregnancies complicated by single fetal intrauterine death in the second or third trimester in our centre from December 1999 to December 2010. Of the total amount of 1996 twin pregnancies attended in our centre, 51 were complicated by single fetal intrauterine death (2.5%). In 68.7% of the cases we found several maternal complications, such as 12.2% of preeclampsia and 12% of coagulopathies. As for the dead foetus, there was a 47% of malformations, a 19.6% of intrauterine fetal growth restriction and there was a 9.8% of cases complicated by twin-twin transfusion syndrome. In the group of the surviving co-twin, 9.8% developed intrauterine growth restriction, 9.8% oligohydramnios and 9.8% Doppler alterations. There was a high risk of prematurity with 43.1% of the births under 34 weeks and 13.7% under 30 weeks of pregnancy. The percentage of caesarean was 64.7%. There was 3 cases of co-twin died intra-uterus, and one more died postpartum. A 10% of the newborns had some kind of neurological disability. It seems that surviving co-twin prognosis is mainly compromised by prematurity and its consequences. There should be more prospective research to inform decision-making and evaluate and control the potential maternal and fetal risks.

Increased aggressive and affiliative display behavior in intrauterine growth restricted (IUGR) baboons

PubMed Central

Huber, Hillary F; Ford, Susan M; Bartlett, Thad Q; Nathanielsz, Peter W

2016-01-01

Background We hypothesized intrauterine growth restricted offspring (IUGR) demonstrate higher rates of aggression and higher dominance ranks than control (CTR) offspring with normal weight at term; if aggressive behavior is advantageous during resource scarcity, developmental programming may lead to an association between aggression and IUGR. Methods We studied 22 group-housed baboons (ages 3-5 years). CTR (male n=8, female n=5) mothers ate ad libitum. IUGR (male n=4, female n=5) mothers were fed 70% feed eaten by CTR mothers during pregnancy and lactation. Results IUGR showed higher rates of aggressive displays (p<0.01) and friendly displays (p<0.02). Dominance ranks and physical aggression rates did not differ between groups. Conclusions High rates of IUGR aggressive display might reflect developmental programming of behavioral phenotypes enhancing fitness. Friendly displays may reflect reconciliation. Potential mechanisms include neurodevelopment and learning. Exploration of IUGR as a risk factor for behavioral patterns is important for developing diagnostic and therapeutic strategies. PMID:25891005

A study investigating obstetricians' and gynaecologists' management of women requesting an intrauterine device.

PubMed

Black, Kirsten I; Sakhaei, Tahereh; Garland, Suzanne M

2010-04-01

Intrauterine methods including the copper intrauterine device (Cu-IUD) and the levonorgestrel intrauterine system (LNG-IUS) provide highly effective long-term reversible contraception. The reasons for relative low use of these methods in Australia compared to many European countries are not clear, but may in part relate to provider reluctance because of outdated knowledge about their safety and efficacy. The aim of this study was to survey Australian Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists about their knowledge of the risks, benefits and mechanisms of action of intrauterine methods. In 2008, we undertook a cross-sectional survey of all Australian Fellows not registered as a subspecialist. The survey was mailed to 1050 practitioners and 701 were returned, comprising a response rate of 67%. Knowledge about the LNG-IUS was significantly better than for the Cu-IUD in terms of correct understanding about mechanism of action (89.3% vs. 30%; P < 0.001) and efficacy (63.2% vs. 33.5%; P < 0.001). According to the WHO, both methods are considered suitable for use in nulliparous women, yet only 39.1% of providers believed the Cu-IUD suitable compared to 69.4% for the LNG-IUS (P < 0.001). When responses were analysed according to time from graduation, many aspects of knowledge about these devices showed a linear trend, with greater accuracy in recent graduates (<10 years) compared with graduates of more than 30 years. Both methods are highly effective, non-user dependent and reversible and deserve greater understanding and consideration for use by Australian practitioners and women.

Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study.

PubMed

Raia-Barjat, Tiphaine; Prieux, Carole; Gris, Jean-Christophe; Chapelle, Céline; Laporte, Silvy; Chauleur, Céline

2017-09-22

The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. Forty-five patients developed a placenta-mediated adverse pregnancy outcome. Plasma levels of sFlt1 and sEng were higher in patients who will experience a preeclampsia at 28, 32, and 36 weeks compared with patients with no complication. The same results were observed for intrauterine growth restriction. Plasma levels of sFlt1 and sEng were not significantly different for patients with preeclampsia compare to patients with intrauterine growth restriction. Patients with early pre-eclampsia (PE) had very high rates of angiogenic factors at 20, 24, and 28 weeks. Patients with late PE and early and late intrauterine growth retardation (IUGR) had high rates at 32 and 36 weeks. In high-risk women, angiogenic factors are disturbed before the onset of preeclampsia and this is true for intrauterine growth restriction.

Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome.

PubMed

Simões, Rui V; Muñoz-Moreno, Emma; Cruz-Lemini, Mónica; Eixarch, Elisenda; Bargalló, Núria; Sanz-Cortés, Magdalena; Gratacós, Eduard

2017-01-01

Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment. The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years. A total of 26 prematurely born intrauterine growth restriction infants (birthweight <10th centile for gestational age), 22 prematurely born but adequate for gestational age controls, and 26 term adequate-for-gestational-age infants underwent brain magnetic resonance imaging and magnetic resonance spectroscopy at 1 year of age during natural sleep, on a 3 Tesla scanner. All brain T1-weighted and diffusion-weighted images were acquired along with short echo time single-voxel proton spectra from the frontal lobe. Magnetic resonance imaging/magnetic resonance spectroscopy data were processed to derive structural, biophysical, and metabolic information, respectively. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales 3rd edition, assessing cognitive, language, motor, socioemotional, and adaptive behavior. Prematurely born intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also

Intrauterine administration of plant oils inhibits luteolysis in the mare.

PubMed

Wilsher, S; Allen, W R

2011-01-01

The maternal recognition of pregnancy (MRP) signal in the mare has not been determined, although oestrogens have been proposed as a potential candidate. To determine effects of intrauterine administration of oestrogen and various oils on cyclic luteolysis in the mare. Intrauterine oestradiol or fatty acids may suppress luteolysis in the cycling mare when administered during late dioestrus. A single 1 ml dose of slow-release oestradiol (10 mg/ml) in fractionated coconut oil was infused into the uterine lumen of cycling mares on Days 6, 8, 10, 12 or 14 post ovulation (n=12 in each group). Four further groups, each of 12 mares, received an intrauterine infusion of either 1 ml of fractionated coconut oil, peanut oil, mineral oil or a slow-release preparation of oestradiol (10 mg/ml) in mineral oil on Day 10 post ovulation. Serial blood samples were assayed for progesterone concentrations to monitor luteal function. Intrauterine administration of oestradiol in fractionated coconut oil showed peak efficacy at Day 10 when luteolysis was delayed in 11/12 (92%) mares. The ability of the treatment to delay luteolysis was not significantly different when administered on Days 8 (9/12; 75%), 12 (10/12; 83%) or 14 (6/12; 50%) of dioestrus, but declined significantly when given on Day 6 (3/12; 25%). Oestradiol was not needed to initiate luteostasis since fractionated coconut oil alone or peanut oil administered at Day 10 induced the same high rate of luteal persistence (11/12; 92% for both oils). In contrast, mineral oil did not prolong luteal lifespan, either when administered alone (2/12; 17%) or combined with oestradiol (3/12; 25%). These results do not unequivocally rule out a possible involvement of embryonic oestrogens in MRP in the mare but suggest it is unlikely. The results demonstrate that plant oils can postpone luteolysis, suggesting they may modulate synthesis or release of prostaglandins from the mare's endometrium. Administration of fractionated coconut or peanut

Activation of peroxisome proliferator-activated receptor-gamma reverses squamous metaplasia and induces transitional differentiation in normal human urothelial cells.

PubMed

Varley, Claire Lucy; Stahlschmidt, Jens; Smith, Barbara; Stower, Michael; Southgate, Jennifer

2004-05-01

We observed that in urothelium, both cornifying and noncornifying forms of squamous metaplasia are accompanied by changes in the localization of the nuclear hormone receptors, peroxisome proliferator activated receptor gamma (PPAR-gamma) and retinoid X receptor (RXR-alpha). To obtain objective evidence for a role for PPAR-gamma-mediated signaling in urothelial differentiation, we examined expression of the cytokeratin isotypes CK13, CK20, and CK14 as indicators of transitional, terminal transitional, and squamous differentiation, respectively, in cultures of normal human urothelial cells. In control culture conditions, normal human urothelial cells showed evidence of squamous differentiation (CK14+, CK13-, CK20-). Treatment with the high-affinity PPAR-gamma agonist, troglitazone (TZ), resulted in gain of CK13 and loss of CK14 protein expression. The effect of TZ was significantly augmented when the autocrine-stimulated epidermal growth factor receptor pathway was inhibited and this resulted in induction of CK20 expression. The RXR-specific inhibitors PA452, HX531, and HX603 inhibited the TZ-induced CK13 expression, supporting a role for RXR in the induction of CK13 expression. Thus, signaling through PPAR-gamma can mediate transitional differentiation of urothelial cells and this is modulated by growth regulatory programs.

Differential Receptor for Advanced Glycation End Products Expression in Preeclamptic, Intrauterine Growth Restricted, and Gestational Diabetic Placentas.

PubMed

Alexander, Kristen L; Mejia, Camilo A; Jordan, Clinton; Nelson, Michael B; Howell, Brian M; Jones, Cameron M; Reynolds, Paul R; Arroyo, Juan A

2016-02-01

Receptor for advanced glycation end products (RAGE) is a receptor implicated in the modulation of inflammation. Inflammation has been associated with pregnancy pathologies including preeclampsia (PE), intrauterine growth restriction (IUGR), and gestational diabetes mellitus (GDM). Our objective was to examine placental RAGE expression in PE, IUGR, and GDM complications. Human placental tissues were obtained for RAGE determination using Q-PCR, immunohistochemistry, and Western blot. Invasive trophoblast cells were cultured and treated with AGES for RAGE activation studies. Compared to control placenta, we observed: (i) decreased RAGE gene expression during GDM, (ii) increased RAGE protein in the PE placenta, and (iii) decreased RAGE protein in the IUGR placenta. In trophoblast cells exposed AGEs, we observed: (i) decreased trophoblast invasion, (ii) increased c-Jun N-terminal kinases (JNK) and Extracellular signal-regulated kinases (ERK), and (iii) increased TNF-α and IL-1β secretion. We conclude that placental RAGE is activated during PE and that RAGE-mediated inflammation in the trophoblast involves increased pro-inflammatory cytokine secretion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination.

PubMed

Lemmens, Louise; Kos, Snjezana; Beijer, Cornelis; Brinkman, Jacoline W; van der Horst, Frans A L; van den Hoven, Leonie; Kieslinger, Dorit C; van Trooyen-van Vrouwerff, Netty J; Wolthuis, Albert; Hendriks, Jan C M; Wetzels, Alex M M

2016-06-01

To investigate the value of sperm parameters to predict an ongoing pregnancy outcome in couples treated with intrauterine insemination (IUI), during a methodologically stable period of time. Retrospective, observational study with logistic regression analyses. University hospital. A total of 1,166 couples visiting the fertility laboratory for their first IUI episode, including 4,251 IUI cycles. None. Sperm morphology, total progressively motile sperm count (TPMSC), and number of inseminated progressively motile spermatozoa (NIPMS); odds ratios (ORs) of the sperm parameters after the first IUI cycle and the first finished IUI episode; discriminatory accuracy of the multivariable model. None of the sperm parameters was of predictive value for pregnancy after the first IUI cycle. In the first finished IUI episode, a positive relationship was found for ≤4% of morphologically normal spermatozoa (OR 1.39) and a moderate NIPMS (5-10 million; OR 1.73). Low NIPMS showed a negative relation (≤1 million; OR 0.42). The TPMSC had no predictive value. The multivariable model (i.e., sperm morphology, NIPMS, female age, male age, and the number of cycles in the episode) had a moderate discriminatory accuracy (area under the curve 0.73). Intrauterine insemination is especially relevant for couples with moderate male factor infertility (sperm morphology ≤4%, NIPMS 5-10 million). In the multivariable model, however, the predictive power of these sperm parameters is rather low. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Caspase Activation in Fetal Rat Brain Following Experimental Intrauterine Inflammation

PubMed Central

Sharangpani, Aditi; Takanohashi, Asako; Bell, Michael J.

2009-01-01

Intrauterine inflammation has been implicated in developmental brain injuries, including the development of periventricular leukomalacia (PVL) and cerebral palsy (CP). Previous studies in our rat model of intrauterine inflammation demonstrated apoptotic cell death in fetal brains within the first 5 days after lipopolysaccharide (LPS) administration to mothers and eventual dysmyelination. Cysteine-containing, aspartate-specific proteases, or caspases, are proteins involved with apoptosis through both intracellular (intrinsic pathway) and extracellular (extrinsic pathway) mechanisms. We hypothesized that cell death in our model would occur mainly via activation of the extrinsic pathway. We further hypothesized that Fas, a member of the tumor necrosis factor receptor (TNFR) superfamily, would be increased and the death inducing signaling complex (DISC) would be detectable. Pregnant rats were injected intracervically with LPS at E15 and immunoblotting, immunohistochemical and immunoprecipitation analyses were performed. The presence of the activated form of the effector caspase (caspase-3) was observed 24 h after LPS administration. Caspase activity assays demonstrated rapid increases in (i) caspases-9 and -10 within 1 h, (ii) caspase-8 at 2 h and (iii) caspase-3 at 4 h. At 24 h after LPS, activated caspase-3+/Fas+ cells were observed within the developing white matter. Lastly, the DISC complex (caspase-8, Fas and Fas-associated Death Domain (FADD)) was observed within 30 min by immunoprecipitation. Apoptosis in our model occurs via both extrinsic and intrinsic pathways, and activation of Fas may play a role. Understanding the mechanisms of cell death in models of intrauterine inflammation may affect development of future strategies to mitigate these injuries in children. PMID:18289516

Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

PubMed Central

Sterle, Igor; Zupančič, Daša; Romih, Rok

2014-01-01

Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns. PMID:24868547

Correlation between urothelial differentiation and sensory proteins P2X3, P2X5, TRPV1, and TRPV4 in normal urothelium and papillary carcinoma of human bladder.

PubMed

Sterle, Igor; Zupančič, Daša; Romih, Rok

2014-01-01

Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

Fluorescence Spectrum and Decay Measurement for Hsil VS Normal Cytology Differentiation in Liquid Pap Smear Supernatant

NASA Astrophysics Data System (ADS)

Vaitkuviene, A.; Gegzna, V.; Juodkazis, S.; Jursenas, S.; Miasojedovas, S.; Kurtinaitiene, R.; Rimiene, J.; Vaitkus, J.

2009-06-01

Cervical smear material contains endo and exocervical cells, mucus and inflammative, immune cells in cases of pathology. Just not destroyed keratinocytes lay on the glass for microscopy. Liquid cytology supernatant apart other diagnostics could be used for photodiagnostic. The spectroscopic parameters suitable for Normal and HSIL cytology groups supernatant differentiation are demonstrated. The dried liquid PAP supernatant fractions—sediment and liquid were investigated. Excitation and emission matrices (EEM), supernatant fluorescence decay measured under 280 nm diode short pulse excitation and fluorescence spectroscopy by excitation with 355 nm laser light were analyzed. The differences between Normal and HSIL groups were statistically proven in the certain spectral regions. Fluorescence decay peculiarities show spectral regions consisting of few fluorophores. Obtained results on fluorescence differences in Normal and HSIL groups' supernatant shows the potency of photodiagnosis application in cervical screening.

Study of molecular mechanisms of learning and memory impairment in neonatal rats post intrauterine distress via the pathway of Tau protein hyperphosphorylation.

PubMed

Wang, X-S; Huang, H

2018-05-01

To explore the reversion of the excitatory amino acid receptor antagonists against the impairment of learning-memory and the hyperphosphorylation of protein Tau induced by fetal intrauterine distress in neonatal rats. The analysis of variance of factorial design set up two intervention factors, fetal intrauterine distress (two levels: no fetal intrauterine distress and a course of fetal intrauterine distress) and the excitatory amino acid receptor antagonists (three levels: Saline; NMDA receptor antagonist MK-801; astragalosides). Forty-eight pregnant rats were randomly divided into six experimental groups (n=8, in each group). After the end of the fetal intrauterine distress, the pregnant rats continued until the birth of newborn rats. When the neonatal rats grow to 12W, the Morris water maze test started in order to evaluate learning-memory. The hippocampus was removed from newborn rats within 1 day after the Morris water maze test finished. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. Besides, the content of protein Tau including Tau5 (total protein Tau), p-PHF1Ser396/404, p-AT8Ser199/202, p-12E8Ser262 in the hippocampus of rats, was examined with the method of immunohistochemistry (IHC) staining (SP). Fetal intrauterine distress and the glutamate ionic receptor blockers could induce the impairment of learning-memory in neonatal rats, extending the evasive latency time and shorten the space exploration time. Both influences present subtract effect. Fetal intrauterine distress could significantly up-regulate the content of glutamate in the hippocampus of neonatal rats, which was not affected by the glutamate ionic receptor blockers. Fetal intrauterine distress and the glutamate ionic receptor blockers did not affect the total protein Tau in the hippocampus of rats. Moreover, fetal intrauterine distress could increase the hyperphosphorylation of protein Tau in the hippocampus of neonatal rats, which

A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures.

PubMed

Huang, Pinxiu; Wei, Lihong; Li, Xinlin

2017-01-01

To investigate the effect of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer (FET) after two or more implantation failures (TIFs). The study was a prospective randomized single-blind study of 161 cycles in patients undergoing FET who had TIFs. The intervention group received an intrauterine injection of 1000 IU of hCG before embryo transfer (ET) (n = 62). A placebo group (n = 49) received an intrauterine injection of physiological saline before ET. A control group (n = 50) did not receive an intrauterine injection. Clinical pregnancy rates, abortion rates, and ongoing pregnancy rates were compared between the three groups. The clinical pregnancy rates were 59.68%, 53.06%, and 32.00% in the hCG group, placebo group, and control group, respectively. The clinical pregnancy rates were significantly higher in the hCG and placebo groups than in the control group. There were no significant differences in the abortion rates among the three groups. An intrauterine administration of hCG before FET significantly improved the pregnancy rates after TIFs. But local injury caused by the operation of intrauterine perfusion may play an important role in improving clinical pregnancy rates.

Chitosan/alginate multilayer film for controlled release of IDM on Cu/LDPE composite intrauterine devices.

PubMed

Tian, Kuan; Xie, Changsheng; Xia, Xianping

2013-09-01

To reduce such side effects as pain and bleeding caused by copper-containing intrauterine device (Cu-IUD), a novel medicated intrauterine device, which is coated with an indomethacin (IDM) delivery system on the surface of copper/low-density polyethylene (Cu/LDPE) composite intrauterine device, has been proposed and developed in the present work. The IDM delivery system is a polyelectrolyte multilayer film, which is composed of IDM containing chitosan and alginate layer by layer, is prepared by using self-assembled polyelectrolyte multilayer method, and the number of the layers of this IDM containing chitosan/alginate multilayer film can be tailored by controlling the cyclic repetition of the deposition process. After the IDM containing chitosan/alginate multilayer film is obtained on the surface of Cu/LDPE composite intrauterine device, its release behavior of both IDM and cupric ion has been studied in vitro. The results show that the release duration of IDM increase with the increasing of thickness of the IDM containing chitosan/alginate multilayer film, and the initial burst release of cupric ion cannot be found in this novel medicated Cu/LDPE composite IUD. These results can be applied to guide the design of novel medicated Cu-IUD with minimal side effects for the future clinical use. Copyright © 2013 Elsevier B.V. All rights reserved.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

PubMed

Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

2018-05-02

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

Normal and Differential SAR Interferometry

DTIC Science & Technology

2005-02-01

incorporating the use of a rough DEM. [ Adragna 1995]. The same technique is also used for flat Earth removal, and for differential interferometry (Cap.5...and F. Adragna , 1994. Radar Interferometric Mapping of Deformation in the Year After the Landers Earthquake, Nature, Vol. 369, pp. 227-230 Massonnet...D., M. Rossi, C. Carmona, F. Adragna , G. Peltzer, K. Feigi, and T. Rabaute, 1993. The Displacement Field of the Landers Earthquake Mapped by Radar

Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression.

PubMed

Yamashita, Michiko; Inoue, Kazuki; Saeki, Noritaka; Ideta-Otsuka, Maky; Yanagihara, Yuta; Sawada, Yuichiro; Sakakibara, Iori; Lee, Jiwon; Ichikawa, Koichi; Kamei, Yoshiaki; Iimura, Tadahiro; Igarashi, Katsuhide; Takada, Yasutsugu; Imai, Yuuki

2018-01-08

Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice ( Uhrf1 Δ Limb/ Δ Limb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1 Δ Limb/ Δ Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1 , which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation. © 2018. Published by The Company of Biologists Ltd.

Optimized surgical treatment for normal pressure hydrocephalus: comparison between gravitational and differential pressure valves.

PubMed

Suchorska, B; Kunz, M; Schniepp, R; Jahn, K; Goetz, C; Tonn, J C; Peraud, A

2015-04-01

In idiopathic normal pressure hydrocephalus (NPH) ventriculoperitoneal (VP) shunt insertion is the method of choice to improve cardinal symptoms such as gait disturbance, urge incontinence and/or dementia. With reduced compliance, the brain of the elderly is prone for overdrainage complications. This was especially true with the use of differential pressure valve implantation. The present study compares clinical outcome and complication rates after VP shunt insertion with differential pressure valves in the early years and gravitational valves since 2005. The authors reviewed patients treated at our institution for NPH since 1995. Differential pressure valves were solely used in the initial years, while the treatment regimen changed to gravitational valves in 2005. Clinical improvement/surgical success rates as well as complications were compared between the two groups. Eighty-nine patients were enrolled for the present study. Mean age at the time of surgery was 73.5 ± 6.3 years. Male patients predominated with 73, compared with 16 female patients. Median follow-up time was 28 ± 26 months. Date of last follow-up was 1st October 2013. Forty-nine patients received a gravitational valve, while 40 were treated with differential pressure valves. In the gravitational group a significant improvement was observed after shunt insertion for gait disorder, cognitive impairment and urge incontinence (p < 0.0001, resp. p = 0.004), while a significant change in the differential pressure group was only seen for gait disorder (p = 0.03) but not for cognition or urinary incontinency (p > 0.05). The risk of hygroma as a sign of shunt overdrainage requiring surgical intervention was significantly higher in the differential pressure group (5 versus 0 in the gravitational group). Patients with NPH treated with gravitational valves in the present cohort showed a more profound improvement in their initial symptoms, including gait disorder, cognitive impairment

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

PubMed

von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

2011-04-01

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Normal and Differential SAR Interferometry

DTIC Science & Technology

2007-02-01

incorporating the use of a rough DEM. [ Adragna 1995]. The same technique is also used for flat Earth removal, and for differential Interferometry (Chap..5...available at http://www.estec.esa.nl/confannoun/99b02/index.html Massonnet, D., K. Feigi, M. Rossi, and F. Adragna , 1994. Radar Interferometric Mapping...of Deformation in the Year After the Landers Earthquake, Nature, Vol. 369, pp. 227-230 Massonnet, D., M. Rossi, C. Carmona, F. Adragna , G. Peltzer

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats

PubMed Central

Goodspeed, Danielle; Seferovic, Maxim D.; Holland, William; Mcknight, Robert A.; Summers, Scott A.; Branch, D. Ware; Lane, Robert H.; Aagaard, Kjersti M.

2015-01-01

Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P < 0.0001) and obese by adulthood (p160: 613 vs. 510 g; P < 0.0001). Dual energy X-ray absorptiometry studies revealed increased central fat mass (Δ+40 g), accompanied by dyslipidemic (>30% elevated, P < 0.05) serum triglycerides (139 mg/dl), very-LDLs (27.8 mg/dl), and fatty acids (632 µM). Hyperglycemic-euglycemic clamp studies and glucose tolerance testing revealed insulin resistance. Conversely, IUGR lineage ENS-fed rats did not manifest MetS, with significantly lower body weight (p160: 410 g), >5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and very-LDLs compared with IUGR control-fed F2 offspring (P < 0.01). Moreover, increased methylation of the IGF-1 P2 transcriptional start site among IUGR lineage F2 offspring was reversed in ENS (P < 0.04). This is an initial demonstration that supplementation along the one-carbon pathway abrogates adult morbidity and associated epigenomic modifications of IGF-1 in a rodent model of multigenerational MetS.—Goodspeed, D., Seferovic, M. D., Holland, W., Mcknight, R. A., Summers, S. A., Branch, D. W., Lane, R. H., Aagaard, K. M. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. PMID:25395450

Progesterone levels and days to luteolysis in mares treated with intrauterine fractionated coconut oil.

PubMed

Diel de Amorim, Mariana; Nielsen, Kayla; Cruz, Raissa Karolliny Salgueiro; Card, Claire

2016-07-15

Intrauterine plant oil infusion, including fractionated coconut oil, has been previously found to be a safe, inexpensive, and reversible method of prolonging the luteal phase in mares when administered on Day 10 of the estrous cycle. Our objective was to understand the uteroovarian response to the administration of fractionated coconut oil infusion in the uterus of diestrous mares. We hypothesized that intrauterine coconut oil administration on Day 10 would prolong luteal life span in a dose-dependent fashion and would result in higher serum progesterone levels than untreated mares at the expected time of luteolysis. Light-horse mares (n = 18) were examined using transrectal palpation and ultrasonography to determine if they had a normal interovulatory interval and were then examined daily in estrus until the day of ovulation (Day 0) and then every other day during an estrous cycle. Jugular blood was drawn on Day 11, Day 13, Day 15, and Day 17, centrifuged, and serum stored until assayed for progesterone (P4; Siemens Coat-a-Count Progesterone RIA, Los Angeles, CA, USA). Mares were randomly assigned to treatment and studied over one to two estrous cycles with a rest cycle after each treatment cycle. Groups were: control (n = 5), fractionated coconut oil 1.0 mL (Miglyol 810; Sasol Oil, Witten, Germany) infused in the uterus with an artificial insemination pipette on Day 10 (Group 1; n = 5) and fractionated coconut oil 0.5 mL infused in the uterus with an embryo transfer gun, on Day 10 (Group 2; n = 5). All statistical analyses were performed using analytical software (Stata SE, version 13.1, College Station, TX, USA) at P < 0.05. Data were first evaluated using the Shapiro-Wilk test for normality. Differences between groups in days to luteolysis (DTL) were examined using analysis of variance and Bonferroni, and the effect of day and treatment on P4 levels were examined using the Kruskal-Wallis and Dunn's all pairwise test. There was a significant

Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

PubMed

McNicholas, Colleen; Swor, Erin; Wan, Leping; Peipert, Jeffrey F

2017-06-01

levonorgestrel intrauterine device is calculated as 0.25 (95% confidence interval, 0.04-1.42) per 100 woman-years; failure rate during the seventh year is 0.43 (95% confidence interval, 0.08-2.39) per 100 woman-years. Among implant users with serum etonogestrel results, the median etonogestrel level was 207.7 pg/mL (range 63.8-802.6 pg/mL) at the time of method expiration, 166.1 pg/mL (range 67.9 25.0-470.5 pg/mL) at the end of the fourth year, and 153.0 pg/mL (range 72.1-538.8 pg/mL) at the end of the fifth year. Median etonogestrel levels were compared by body mass index at each time point and a statistical difference was noted at the end of 4 years of use with overweight women having the highest serum etonogestrel (195.9; range 25.0-450.5 pg/mL) when compared to normal (178.9; range 87.0-463.7 pg/mL) and obese (137.9; range 66.0-470.5 pg/mL) women (P = .04). This study indicates that the contraceptive implant and 52-mg hormonal intrauterine device continue to be highly effective for at least 2 additional years of use. Serum etonogestrel evaluation demonstrates median levels remain above the ovulation threshold of 90 pg/mL for women in all body mass index classes. Copyright © 2017 Elsevier Inc. All rights reserved.

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

PubMed

Zhou, Huimei; Cao, Dongyan; Yang, Jiaxin; Shen, Keng; Lang, Jinghe

2017-07-01

The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is

Raman spectroscopy differentiates squamous cell carcinoma (SCC) from normal skin following treatment with a high-powered CO2 laser.

PubMed

Fox, Sara A; Shanblatt, Ashley A; Beckman, Hugh; Strasswimmer, John; Terentis, Andrew C

2014-12-01

The number of cases of non-melanoma skin cancer (NMSC), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), continues to rise as the aging population grows. Mohs micrographic surgery has become the treatment of choice in many cases but is not always necessary or feasible. Ablation with a high-powered CO2 laser offers the advantage of highly precise, hemostatic tissue removal. However, confirmation of complete cancer removal following ablation is difficult. In this study we tested for the first time the feasibility of using Raman spectroscopy as an in situ diagnostic method to differentiate NMSC from normal tissue following partial ablation with a high-powered CO2 laser. Twenty-five tissue samples were obtained from eleven patients undergoing Mohs micrographic surgery to remove NMSC tumors. Laser treatment was performed with a SmartXide DOT Fractional CO2 Laser (DEKA Laser Technologies, Inc.) emitting a wavelength of 10.6 μm. Treatment levels ranged from 20 mJ to 1200 mJ total energy delivered per laser treatment spot (350 μm spot size). Raman spectra were collected from both untreated and CO2 laser-treated samples using a 785 nm diode laser. Principal Component Analysis (PCA) and Binary Logistic Regression (LR) were used to classify spectra as originating from either normal or NMSC tissue, and from treated or untreated tissue. Partial laser ablation did not adversely affect the ability of Raman spectroscopy to differentiate normal from cancerous residual tissue, with the spectral classification model correctly identifying SCC tissue with 95% sensitivity and 100% specificity following partial laser ablation, compared with 92% sensitivity and 60% selectivity for untreated NMSC tissue. The main biochemical difference identified between normal and NMSC tissue was high levels of collagen in the normal tissue, which was lacking in the NMSC tissue. The feasibility of a combined high-powered CO2 laser ablation, Raman diagnostic procedure for the

Control of intrauterine fluid pressure during operative hysteroscopy.

PubMed

Shirk, G J; Gimpelson, R J

1994-05-01

To evaluate the safety of a commonly used piston pump that controls the infusion pressure of low-viscosity fluids in a continuous-flow hysteroscopic system during operative hysteroscopy. Consecutive patients requiring operative hysteroscopy. Three hospital facilities in the Midwest. Sequential sample of 250 women who underwent operative hysteroscopy. Endometrial ablations, resection of submucosal or pedunculated uterine leiomyomata with or without endometrial ablation, polyp resections, metroplasty, and lysis of synechiae. The most serious complication of operative hysteroscopy is fluid overload due to intravasation into the patient's vascular system. Low-viscosity fluids were infused by the Zimmer Controlled Distention Irrigation System. The instrument uses a closed-feedback loop to monitor cavity pressure and automatically regulates the flow to maintain the set point pressure. It is designed to operate in a pressure range of 0 to 80 mm Hg and at flows in excess of 450 ml/minute. In 250 operative hysteroscopies no fluid complications occurred when intrauterine pressure was maintained below 80 mm Hg. No clinically significant differences in intravasation were seen in any type of operative hysteroscopy. This controlled mechanical pump system with exact intrauterine pressure measurement reduced many technical difficulties associated with low-viscosity media, and created a safe environment for the media's use in operative hysteroscopy.

Increased nuchal traslucency in normal karyotype fetuses

PubMed Central

De Domenico, Roberta; Faraci, Marianna; Hyseni, Entela; Di Prima, Fosca A. F.; Valenti, Oriana; Monte, Santo; Giorgio, Elsa; Renda, Eliana

2011-01-01

Nuchal traslucency (NT) measurement between 11 and 14 weeks’ gestation is a reliable marker for chromosomal abnormalities, including trisomy 21. However, even if conventional karyotyping is normal, increased NT is a predictive value of adverse pregnancy outcome, because it is associated with several fetal malformations, congenital heart defects, genetic syndromes, intrauterine death and miscarriages; the majority of these structural anomalies are undetectable before birth. The risk is proportional to the nuchal translucency thickness, in fact it statistically increases after measurement reaching 3.5 mm or more. However, when these chromosomally normal fetuses with an enlarged NT survive, even if a detailed ultrasound examination and echocardiography fail to reveal any abnormalities, their uneventful outcome and postnatal developmental delay will be not statistically increased when compared to the general population. These parents should be confidently reassured that the residual chance of structural anomalies and abnormal neurodevelopment may not be higher than in the general population. PMID:22439071

Neurodegenerative changes and apoptosis induced by intrauterine and extrauterine exposure of radiofrequency radiation.

PubMed

Güler, Göknur; Ozgur, Elcin; Keles, Hikmet; Tomruk, Arin; Vural, Sevil Atalay; Seyhan, Nesrin

2016-09-01

Adverse health effects of radiofrequency radiation (RFR) on the ongoing developmental stages of children from conception to childhood are scientifically anticipated subject. This study was performed to identify the effects of global system for mobile communications (GSM) modulated mobile phone like RFR in 1800MHz frequency on oxidative DNA damage and lipid peroxidation beside the apoptotic cell formation, using histopathological and immunohistochemical methods in the brain tissue of 1-month-old male and female New Zealand White rabbits that were exposed to these fields at their mother's womb and after the birth. Oxidative DNA damage and lipid peroxidation levels were investigated by measuring the 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels, respectively. Histopathological changes were observed using by hematoxylin and eosin (HE) staining. Apoptotic cells were detected in the examined organs by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. For both male and female infants; 8-OHdG levels increased in the group exposed to RFR in both intrauterine and extrauterine periods compared to the infants that were never exposed to RFR and the ones were exposed when they reached one month of age (p<0.05). MDA results were different for male and female rabbits. There was no difference between all female infant groups (p>0.05), while only intrauterine exposure significantly causes MDA level increase for the male infants. HE staining revealed mild lessions in neuronal necrobiosis in brain tissues of female rabbits that had only intaruterine exposure and male rabbits had only extrauterine exposure. Gliosis were mildly positive in brain tissues of rabbits that are exposed only intrauterine period, also the group exposed both intrauterine and extrauterine periods. However, there was no apoptotic change detected by TUNEL staining in the brain tissues of all groups. Copyright © 2015 Elsevier B.V. All rights reserved.

Predicting the intrauterine fetal death of fetuses with cystic hygroma in early pregnancy.

PubMed

Shimura, Mai; Ishikawa, Hiroshi; Nagase, Hiromi; Mochizuki, Akihiko; Sekiguchi, Futoshi; Koshimizu, Naho; Itai, Toshiyuki; Odagami, Mizuha

2018-01-11

We investigated whether it was possible to predict the prognosis of fetuses with cystic hygroma in early pregnancy based on the degree of neck thickening. We retrospectively analyzed 57 singleton pregnancies with fetuses with cystic hygroma who were examined before the 22nd week of pregnancy. The fetuses were categorized according to the outcome, structural abnormalities at birth, and chromosomal abnormalities. Here, we proposed a new sonographic predictor with which we assessed neck thickening by dividing the width of the neck thickening by the biparietal diameter, which is expressed as the cystic hygroma width/biparietal diameter ratio. The median cystic hygroma width/biparietal diameter ratio in the intrauterine fetal death group (0.51) was significantly higher than that in the live birth group (0.27). No significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the structural abnormalities group at birth and the no structural abnormalities group, and no significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the chromosomal abnormality group and the no chromosomal abnormality group. We used receiver operating characteristic analysis to evaluate the cystic hygroma width/biparietal diameter ratio to predict intrauterine fetal death. When the cystic hygroma width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is possible to predict intrauterine fetal death in fetuses with cystic hygroma in early pregnancy if cystic hygroma width/biparietal diameter ratio is measured. However, even if cystic hygroma width/biparietal diameter ratio is measured, predicting the presence or absence of a structural abnormality at birth or a chromosomal abnormality is difficult. © 2018 Japanese Teratology Society.

Predictive factors for intrauterine growth restriction.

PubMed

Albu, A R; Anca, A F; Horhoianu, V V; Horhoianu, I A

2014-06-15

Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies.

Intrauterine photoacoustic and ultrasound imaging probe

NASA Astrophysics Data System (ADS)

Miranda, Christopher; Barkley, Joel; Smith, Barbara S.

2018-04-01

Intrauterine photoacoustic and ultrasound imaging are probe-based imaging modalities with translational potential for use in detecting endometrial diseases. This deep-tissue imaging probe design allows for the retrofitting of commercially available endometrial sampling curettes. The imaging probe presented here has a 2.92-mm diameter and approximate length of 26 cm, which allows for entry into the human endometrial cavity, making it possible to use photoacoustic imaging and high-resolution ultrasound to characterize the uterus. We demonstrate the imaging probes' ability to provide structural information of an excised pig uterus using ultrasound imaging and detect photoacoustic signals at a radial depth of 1 cm.

Intrauterine hematomas in the second and third trimesters associated with adverse pregnancy outcomes: a retrospective study.

PubMed

Ji, Wanqing; Li, Weidong; Mei, Shanshan; He, Ping

2017-09-01

To carry out a retrospective study of the clinical features of patients with intrauterine hematoma in the second and third trimesters, and discuss the risk factors for poor pregnancy outcomes. A total of 398 patients who underwent routine examination in our hospital from January 2011 to December 2015 were classified into normal pregnancy (NP) group (N = 265) and adverse pregnancy (AP) group (N = 133), according to their pregnancy outcomes. Maternal clinical demographics, gestational age, location of hematoma, volume of hematoma, and accompanying contraction and vaginal bleeding were recorded. The average age of pregnant women in the NP and AP groups was 28.25 ± 4.06 and 29.5 ± 5.06 years, respectively (p = 0.007). Gestational age at first detection of hematoma was 15.11 ± 5.13 weeks in the NP group compared with 21.22 ± 8.25 weeks in the AP group (p < 0.001). In the AP group, the incidence of retroplacental hematoma (54.1%) and palpable contractions (62.8%) was significantly higher than in the NP group (25.7% and 12.1%, respectively; p < 0.01). However, similar maternal parity or history of delivery, volume of hematoma and incidence of vaginal bleeding were found. Intrauterine hematoma in the second and third trimesters is a sign of pathological pregnancy, resulting in adverse outcomes. Maternal age, gestational age at first diagnosis, location of hematoma and accompanying contraction are risk factors for poor pregnancy outcomes.

Soluble CD30 in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2010-11-01

This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Placental pathology in early intrauterine growth restriction associated with maternal hypertension.

PubMed

Veerbeek, J H W; Nikkels, P G J; Torrance, H L; Gravesteijn, J; Post Uiterweer, E D; Derks, J B; Koenen, S V; Visser, G H A; Van Rijn, B B; Franx, A

2014-09-01

To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities. Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth <34 weeks of a baby with a weight <10th percentile for gestational age. Umbilical artery end diastolic flow was classified as being either present or absent/reversed (AREDF). Data were stratified into intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria. Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p < 0.05). Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Does intrauterine injection of low-molecular-weight heparin improve the clinical pregnancy rate in intracytoplasmic sperm injection?

PubMed Central

El-Faissal, Yahia; Aboulghar, Mona; Mansour, Ragaa; Serour, Gamal I; Aboulghar, Mohamed

2016-01-01

Objective Heparin can modulate proteins, and influence processes involved in implantation and trophoblastic development. This study aimed to assess the improvement of clinical pregnancy and implantation rates after local intrauterine injection of low-molecular-weight heparin (LMWH) in patients undergoing intracytoplasmic sperm injection (ICSI). Methods A randomised case/control design was followed in women scheduled for ICSI. The study arm was injected with intrauterine LMWH during mock embryo transfer immediately following the ovum pickup procedure, while the control arm was given an intrauterine injection with a similar volume of tissue culture media. Side effects, the clinical pregnancy rate, and the implantation rate were recorded. Results The pregnancy rate was acceptable (33.9%) in the LMWH arm with no significant reported side effects, confirming the safety of the intervention. No statistically significant differences were found in the clinical pregnancy and implantation rates between both groups (p=0.182 and p=0.096, respectively). The odds ratio of being pregnant after intrauterine injection with LMWH compared to the control group was 0.572 (95% confidence interval [CI], 0.27−1.22), while the risk ratio was 0.717 (95% CI, 0.46−1.13; p=0.146). No statistical significance was found between the two groups in other factors affecting implantation, such as day of transfer (p=0.726), number of embryos transferred (p=0.362), or embryo quality. Conclusion Intrauterine injection of LMWH is a safe intervention, but the dose used in this study failed to improve the outcome of ICSI. Based on its safety, further research involving modification of the dosage and/or the timing of administration could result in improved ICSI success rates. PMID:28090465

The Local and Systemic Immune Response to Intrauterine LPS in the Prepartum Mouse1

PubMed Central

Edey, Lydia F.; O'Dea, Kieran P.; Herbert, Bronwen R.; Hua, Renyi; Waddington, Simon N.; MacIntyre, David A.; Bennett, Philip R.; Takata, Masao; Johnson, Mark R.

2016-01-01

Inflammation plays a key role in human term and preterm labor (PTL). Intrauterine LPS has been widely used to model inflammation-induced complications of pregnancy, including PTL. It has been shown to induce an intense myometrial inflammatory cell infiltration, but the role of LPS-induced inflammatory cell activation in labor onset and fetal demise is unclear. We investigated this using a mouse model of PTL, where an intrauterine injection of 10 μg of LPS (serotype 0111:B4) was given at E16 of CD1 mouse pregnancy. This dose induced PTL at an average of 12.7 h postinjection in association with 85% fetal demise. Flow cytometry showed that LPS induced a dramatic systemic inflammatory response provoking a rapid and marked leucocyte infiltration into the maternal lung and liver in association with increased cytokine levels. Although there was acute placental inflammatory gene expression, there was no corresponding increase in fetal brain inflammatory gene expression until after fetal demise. There was marked myometrial activation of NFκB and MAPK/AP-1 systems in association with increased chemokine and cytokine levels, both of which peaked with the onset of parturition. Myometrial macrophage and neutrophil numbers were greater in the LPS-injected mice with labor onset only; prior to labor, myometrial neutrophils and monocytes numbers were greater in PBS-injected mice, but this was not associated with an earlier onset of labor. These data suggest that intrauterine LPS induces parturition directly, independent of myometrial inflammatory cell infiltration, and that fetal demise occurs without fetal inflammation. Intrauterine LPS provokes a marked local and systemic inflammatory response but with limited inflammatory cell infiltration into the myometrium or placenta. PMID:27760748

Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth.

PubMed

Burd, Irina; Zhang, Fan; Dada, Tahani; Mishra, Manoj K; Borbiev, Talaibek; Lesniak, Wojciech G; Baghlaf, Haitham; Kannan, Sujatha; Kannan, Rangaramanujam M

2014-08-01

Intrauterine inflammation is associated with preterm birth and can lead to fetal neuroinflammation and neurobehavioral disorders in newborns. Dendrimers can intrinsically target and deliver drugs for the treatment of neuroinflammation. We explore whether hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines can be delivered to the fetus by intra-amniotic administration, in a mouse model of intrauterine inflammation. The time-dependent accumulation of G4-OH-fluorophore conjugate was quantified by fluorescence. These studies suggest that, after intra-amniotic administration, there is significant accumulation of dendrimer in the fetus gut and brain. In addition, there is some fetal-maternal transport of the dendrimer. Confocal microscopy confirmed the presence of G4-OH in the fetal brain, with a large accumulation in the brain blood vessels and the brain parenchyma, and some microglial uptake. We believe that intra-amniotic administration of G4-OH-drug nanomedicines may enable the treatment of diseases related to intrauterine inflammation and fetal neuroinflammation. Using a mouse model of intrauterin inflammation leading to neuroinflammation in the fetus, these investigators demonstrate that intra-amniotic delivery of hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines may provide an effective method in preventing this complication. Copyright © 2014 Elsevier Inc. All rights reserved.

ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR.

PubMed

Wu, Yanming; Chen, Xiao; Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

2014-01-01

Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

ITE and TCDD Differentially Regulate the Vascular Remodeling of Rat Placenta via the Activation of AhR

PubMed Central

Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

2014-01-01

Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

Comparing the normalization methods for the differential analysis of Illumina high-throughput RNA-Seq data.

PubMed

Li, Peipei; Piao, Yongjun; Shon, Ho Sun; Ryu, Keun Ho

2015-10-28

, Med, TMM, DESeq, and Q did not noticeably improve gene expression normalization, regardless of read length. Other normalization methods were more efficient when alignment accuracy was low; Sailfish with RPKM gave the best normalization results. When alignment accuracy was high, RC was sufficient for gene expression calculation. And we suggest ignoring poly-A tail during differential gene expression analysis.

Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility.

PubMed

Styer, Aaron K; Jin, Susan; Liu, Dan; Wang, Baisong; Polotsky, Alex J; Christianson, Mindy S; Vitek, Wendy; Engmann, Lawrence; Hansen, Karl; Wild, Robert; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Christy, Alicia; Diamond, Michael P; Eisenberg, Esther; Zhang, Heping; Santoro, Nanette

2017-03-01

To investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility. Secondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI. Reproductive Medicine Network clinical sites. Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved. Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates. A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids. No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility. NCT01044862. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Differentiating normal and disordered personality using the General Assessment of Personality Disorder (GAPD).

PubMed

Hentschel, Annett G; John Livesley, W

2013-05-01

Criteria to differentiate personality disorder from extremes of normal personality variations are important given growing interest in dimensional classification because an extreme level of a personality dimension does not necessarily indicate disorder. The DSM-5 proposed classification of personality disorder offers a definition of general personality disorder based on chronic interpersonal and self/identity pathology. The ability of this approach to differentiate personality disorder from other mental disorders was evaluated using a self-report questionnaire, the General Assessment of Personality Disorder (GAPD). This measure was administered to a sample of psychiatric patients (N = 149) from different clinical sub-sites. Patients were divided into personality disordered and non-personality disordered groups on the basis of the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). The results showed a hit rate of 82% correct identified patients and a good accuracy of the predicted model. There was a substantial agreement between SCID-II interview and GAPD personality disorder diagnoses. The GAPD appears to predict personality disorder in general, which provides support of the DSM-5 general diagnostic criteria of personality disorder. Copyright © 2012 John Wiley & Sons, Ltd.

Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice.

PubMed

Yin, Jinbao; Liu, Su; Yu, Jing; Wu, Bing

2017-07-01

Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and β-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.

Data Mining of Determinants of Intrauterine Growth Retardation Revisited Using Novel Algorithms Generating Semantic Maps and Prototypical Discriminating Variable Profiles

PubMed Central

Buscema, Massimo; Grossi, Enzo; Montanini, Luisa; Street, Maria E.

2015-01-01

Objectives Intra-uterine growth retardation is often of unknown origin, and is of great interest as a “Fetal Origin of Adult Disease” has been now well recognized. We built a benchmark based upon a previously analysed data set related to Intrauterine Growth Retardation with 46 subjects described by 14 variables, related with the insulin-like growth factor system and pro-inflammatory cytokines, namely interleukin -6 and tumor necrosis factor -α. Design and Methods We used new algorithms for optimal information sorting based on the combination of two neural network algorithms: Auto-contractive Map and Activation and Competition System. Auto-Contractive Map spatializes the relationships among variables or records by constructing a suitable embedding space where ‘closeness’ among variables or records reflects accurately their associations. The Activation and Competition System algorithm instead works as a dynamic non linear associative memory on the weight matrices of other algorithms, and is able to produce a prototypical variable profile of a given target. Results Classical statistical analysis, proved to be unable to distinguish intrauterine growth retardation from appropriate-for-gestational age (AGA) subjects due to the high non-linearity of underlying functions. Auto-contractive map succeeded in clustering and differentiating completely the conditions under study, while Activation and Competition System allowed to develop the profile of variables which discriminated the two conditions under study better than any other previous form of attempt. In particular, Activation and Competition System showed that ppropriateness for gestational age was explained by IGF-2 relative gene expression, and by IGFBP-2 and TNF-α placental contents. IUGR instead was explained by IGF-I, IGFBP-1, IGFBP-2 and IL-6 gene expression in placenta. Conclusion This further analysis provided further insight into the placental key-players of fetal growth within the insulin-like growth

Exposure to intrauterine inflammation alters metabolomic profiles in the amniotic fluid, fetal and neonatal brain in the mouse

PubMed Central

Barila, Guillermo O.; Hester, Michael S.; Elovitz, Michal A.

2017-01-01

Introduction Exposure to prenatal inflammation is associated with diverse adverse neurobehavioral outcomes in exposed offspring. The mechanism by which inflammation negatively impacts the developing brain is poorly understood. Metabolomic profiling provides an opportunity to identify specific metabolites, and novel pathways, which may reveal mechanisms by which exposure to intrauterine inflammation promotes fetal and neonatal brain injury. Therefore, we investigated whether exposure to intrauterine inflammation altered the metabolome of the amniotic fluid, fetal and neonatal brain. Additionally, we explored whether changes in the metabolomic profile from exposure to prenatal inflammation occurs in a sex-specific manner in the neonatal brain. Methods CD-1, timed pregnant mice received an intrauterine injection of lipopolysaccharide (50 μg/dam) or saline on embryonic day 15. Six and 48 hours later mice were sacrificed and amniotic fluid, and fetal brains were collected (n = 8/group). Postnatal brains were collected on day of life 1 (n = 6/group/sex). Global biochemical profiles were determined using ultra performance liquid chromatography/tandem mass spectrometry (Metabolon Inc.). Statistical analyses were performed by comparing samples from lipopolysaccharide and saline treated animals at each time point. For the P1 brains, analyses were stratified by sex. Results/Conclusions Exposure to intrauterine inflammation induced unique, temporally regulated changes in the metabolic profiles of amniotic fluid, fetal brain and postnatal brain. Six hours after exposure to intrauterine inflammation, the amniotic fluid and the fetal brain metabolomes were dramatically altered with significant enhancements of amino acid and purine metabolites. The amniotic fluid had enhanced levels of several members of the (hypo) xanthine pathway and this compound was validated as a potential biomarker. By 48 hours, the number of altered biochemicals in both the fetal brain and the amniotic

Role of peripheral blood mononuclear cell transportation from mother to baby in HBV intrauterine infection.

PubMed

Shao, Qingliang; Zhao, Xiaxia; Yao Li, M D

2013-12-01

We aimed to investigate the role of peripheral blood mononuclear cell transportation from mother to baby in hepatitis B virus (HBV) intrauterine infection. Thirty HBsAg-positive pregnant women in the second trimester and their aborted fetuses were included in this study. Enzyme-linked-immunosorbent-assay was utilized to detect HBsAg in the peripheral blood of pregnant women and the femoral vein blood of their aborted fetuses. HBV-DNA in serum and peripheral blood mononuclear cells (PBMC) and GSTM1 alleles of pregnant women and their aborted fetuses were detected by nested polymerase chain reaction (PCR) and seminested PCR, respectively. We also examined the location of placenta HBsAg and HBcAb using immunohistochemical staining. The expression of placenta HBV-DNA was detected by in situ hybridization. For the 30 aborted fetuses, the HBV intrauterine infection rate was 43.33%. The HBV-positive rates of HBsAg in peripheral blood, serum, and PBMC were 10% (3/30), 23.33% (7/30), and 33.33% (10/30), respectively. Maternal-fetal PBMC transport was significantly positively correlated with fetal PBMC HBV-DNA (P = 0.004). Meanwhile, the rates of HBV infection gradually decreased from the maternal side to the fetus side of placenta (decidual cells > trophoblastic cells > villous mesenchymal cells > villous capillary endothelial cells). However, no significant correlation between placenta HBV infection and HBV intrauterine infection was observed (P = 0.410). HBV intrauterine infection was primarily due to peripheral blood mononuclear cell maternal-fetal transportation in the second trimester in pregnant women.

Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis.

PubMed

Chen, Juncao; Gong, Xiaoyuan; Chen, Pingyang; Luo, Kaiju; Zhang, Xiuquan

2016-08-16

Intrauterine growth restriction (IUGR) is associated with perinatal morbidity and mortality. Several clinical trials have reported L-arginine and sildenafil citrate had effect on intrauterine growth restriction fetuses. A meta-analysis of available randomized controlled trials (RCTs) was conducted to investigate the effects of L-arginine and sildenafil citrate on major clinical outcomes of IUGR fetuses. Systematically searched Medline, Embase, the Cochrane Library, and Clinical Trials, references of retrieved articles, and conference proceedings from 1960 to 2015. We included randomized controlled trials assessing the effects of L-arginine and sildenafil citrate on IUGR. Outcomes analyzed were the birth weight, gestational age at labor, Apgar score at 1and 5 min, the ratio of NRDS, the ratio of ICH and neonatal death, etc. Ten trials were included. Nine trials (576 patients) compared L-arginine with either placebo or no intervention. In the L-arginine treatment groups of the L-arginine trials, there was a significant increase in fetal birth weight (SMD 0.41, 95 % CI [0.24,0.58]), gestational age (SMD 0.30, 95 % CI [0.07,0.54]); L-arginine treatment group have a significant reduction in the ratio of neonatal respiratory distress syndrome (P = 0.009), intracranial hemorrhage of fetuses (P = 0.002), but the number of included studies and people on these outcomes are small. As only one trial (41 patients) compared sildenafil citrate with placebo, it was too small for reliable conclusions about possible differential effects could be drawn. The results of this meta-analysis showed that L-arginine increased birth weight and prolonged gestational age at labor of IUGR fetuses. However, further large-scale RCTs are needed to adequately assess the effect of L-arginine and Sildenafil citrate on clinical outcomes, because the number of study may be small.

Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery.

PubMed

Maul, H; Maner, W L; Olson, G; Saade, G R; Garfield, R E

2004-05-01

The study was conducted to investigate whether the strength of uterine contractions monitored invasively by intrauterine pressure catheter could be determined from transabdominal electromyography (EMG) and to estimate whether EMG is a better predictor of true labor compared to tocodynamometry (TOCO). Uterine EMG was recorded from the abdominal surface in laboring patients simultaneously monitored with an intrauterine pressure catheter (n = 13) or TOCO (n = 24). Three to five contractions per patient and corresponding electrical bursts were randomly selected and analyzed (integral of intrauterine pressure; integral, frequency, amplitude of contraction curve on TOCO; burst energy for EMG). The Mann-Whitney test, Spearman correlation and receiver operator characteristics (ROC) analysis were used as appropriate (significance was assumed at a value of p < 0.05). EMG correlated strongly with intrauterine pressure (r = 0.764; p = 0.002). EMG burst energy levels were significantly higher in patients who delivered within 48 h compared to those who delivered later (median [25%/75%]: 96,640 [26,520-322,240] vs. 2960 [1560-10,240]; p < 0.001), whereas none of the TOCO parameters were different. In addition, burst energy levels were highly predictive of delivery within 48 h (AUC = 0.9531; p < 0.0001). EMG measurements correlated strongly with the strength of contractions and therefore may be a valuable alternative to invasive measurement of intrauterine pressure. Unlike TOCO, transabdominal uterine EMG can be used reliably to predict labor and delivery.

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy.

PubMed

Cohen, Emily; Wong, Flora Y; Horne, Rosemary S C; Yiallourou, Stephanie R

2016-06-01

Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease.

Differential diagnosis of normal pressure hydrocephalus by MRI mean diffusivity histogram analysis.

PubMed

Ivkovic, M; Liu, B; Ahmed, F; Moore, D; Huang, C; Raj, A; Kovanlikaya, I; Heier, L; Relkin, N

2013-01-01

Accurate diagnosis of normal pressure hydrocephalus is challenging because the clinical symptoms and radiographic appearance of NPH often overlap those of other conditions, including age-related neurodegenerative disorders such as Alzheimer and Parkinson diseases. We hypothesized that radiologic differences between NPH and AD/PD can be characterized by a robust and objective MR imaging DTI technique that does not require intersubject image registration or operator-defined regions of interest, thus avoiding many pitfalls common in DTI methods. We collected 3T DTI data from 15 patients with probable NPH and 25 controls with AD, PD, or dementia with Lewy bodies. We developed a parametric model for the shape of intracranial mean diffusivity histograms that separates brain and ventricular components from a third component composed mostly of partial volume voxels. To accurately fit the shape of the third component, we constructed a parametric function named the generalized Voss-Dyke function. We then examined the use of the fitting parameters for the differential diagnosis of NPH from AD, PD, and DLB. Using parameters for the MD histogram shape, we distinguished clinically probable NPH from the 3 other disorders with 86% sensitivity and 96% specificity. The technique yielded 86% sensitivity and 88% specificity when differentiating NPH from AD only. An adequate parametric model for the shape of intracranial MD histograms can distinguish NPH from AD, PD, or DLB with high sensitivity and specificity.

Human cytomegalovirus infection interferes with the maintenance and differentiation of trophoblast progenitor cells of the human placenta.

PubMed

Tabata, Takako; Petitt, Matthew; Zydek, Martin; Fang-Hoover, June; Larocque, Nicholas; Tsuge, Mitsuru; Gormley, Matthew; Kauvar, Lawrence M; Pereira, Lenore

2015-05-01

impairment, and pregnancy complications, including intrauterine growth restriction, preterm delivery, and stillbirth. Currently, there is neither a vaccine nor any approved treatment for congenital HCMV infection during gestation. The molecular mechanisms underlying structural deficiencies in the placenta that undermine fetal development are poorly understood. Here we report that HCMV replicates in trophoblast progenitor cells (TBPCs)-precursors of the mature placental cells, syncytiotrophoblasts and cytotrophoblasts, in chorionic villi-in clinical cases of congenital infection. Virus replication in TBPCs in vitro dysregulates key proteins required for self-renewal and differentiation and inhibits normal division and development into mature placental cells. Our findings provide insights into the underlying molecular mechanisms by which HCMV replication interferes with placental maturation and transport functions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Reduced angiogenic factor expression in intrauterine fetal growth restriction using semiquantitative immunohistochemistry and digital image analysis.

PubMed

Alahakoon, Thushari I; Zhang, Weiyi; Arbuckle, Susan; Zhang, Kewei; Lee, Vincent

2018-05-01

To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining. © 2018 Japan Society of Obstetrics and Gynecology.

Committee Opinion No. 642: Increasing Access to Contraceptive Implants and Intrauterine Devices to Reduce Unintended Pregnancy.

PubMed

2015-10-01

Unintended pregnancy persists as a major public health problem in the United States. Although lowering unintended pregnancy rates requires multiple approaches, individual obstetrician-gynecologists may contribute by increasing access to contraceptive implants and intrauterine devices. Obstetrician-gynecologists should encourage consideration of implants and intrauterine devices for all appropriate candidates, including nulliparous women and adolescents. Obstetrician-gynecologists should adopt best practices for long-acting reversible contraception insertion. Obstetrician-gynecologists are encouraged to advocate for coverage and appropriate payment and reimbursement for every contraceptive method by all payers in all clinically appropriate circumstances.

Endometrial Injury May Increase the Pregnancy Rate in Patients Undergoing Intrauterine Insemination: An Interventional Randomized Clinical Trial.

PubMed

Bahaa Eldin, Ahmed M; Abdelmaabud, Karim H; Laban, Mohamed; Hassanin, Alaa S; Tharwat, Ahmed A; Aly, Tarek R; Elbohoty, Ahmed E; Elsayed, Helmy M; Ibrahim, Ahmed M; Ibrahim, Mohammed E; Sabaa, Haitham M; Abdelrazik, Azza A; Abdelhady, Ibrahim

2016-10-01

This study aimed to investigate the effect of endometrial injury using Pipelle catheter in the follicular phase (cycle day 5, 6, or 7) of the stimulation cycle on pregnancy rates in patients undergoing intrauterine insemination. This prospective randomized controlled study was carried out in the Assisted Reproductive Technology Unit of Ain Shams University Maternity Hospital, Cairo, Egypt, from July 1, 2013 to August 31, 2015. Three hundred sixty women, 20 to 35 years of age, with patent fallopian tubes, mild male factor infertility, or unexplained infertility were recruited. Participants were allocated randomly into 2 groups: experimental arm and control arm. Women in the experimental arm underwent endometrial biopsy using a Pipelle catheter on day 5, 6, or 7 of the stimulation cycle combined with intrauterine insemination. Women in the control group underwent intrauterine insemination with no endometrial biopsy done. The primary outcomes were the clinical and chemical pregnancy rates. Data of 344 participants were statistically analyzed. The chemical pregnancy rate was 23.66% in the experimental arm and 10.85% in the control arm (P = .002). The clinical pregnancy rate was 18.93% in the experimental arm and 7.42% in the control arm (P = .003). Endometrial injury using a Pipelle catheter in the stimulation cycle may improve pregnancy rates in women undergoing intrauterine insemination. © The Author(s) 2016.

Intrauterine Inflated Foley's Catheter Balloon in the Management of Abnormally Invasive Placenta Previa: A Case-Control Study.

PubMed

Thabet, Mahmoud; Abdelhafez, Mohamed Sayed; Fyala, Emad Ahmed

2018-06-01

To describe the use of intrauterine inflated Foley's catheter balloon for control of postpartum hemorrhage (PPH) during cesarean section (CS) in cases of abnormally invasive placenta previa aiming to preserve the uterus. Retrospective case-control study of the data of women who underwent elective CS on abnormally adherent placenta previa was carried out. Women in whom inflated Foley's catheter balloon was used for control of PPH during CS ( n  = 40) were compared with a control group of women who underwent elective CS by the same technique but without use of intrauterine catheter balloon ( n  = 38). Use of intrauterine inflated Foley's catheter balloon significantly reduced the estimated amount of blood loss ( P  = 0.008), amounts of crystalloids, colloids and packed red blood cells transfusion ( P  = 0.025, 0.017 and 0.022, respectively), and the need for bilateral internal iliac artery (IIA) ligation ( P  = 0.016). No significant difference was observed between both groups regarding the use of massive transfusion protocol, performing cesarean hysterectomy, relaparotomy, and admission to the intensive care unit. Application of an intrauterine inflated Foley's catheter balloon during CS in cases of morbidly adherent placenta previa helps to control PPH with preservation of the uterus and decreases the need for the invasive IIA ligation.

Kell hemolytic disease of the fetus. Combination treatment with plasmapheresis and intrauterine blood transfusion.

PubMed

Lakhwani, S; Machado, P; Pecos, P; Coloma, M; Rebollo, S; Raya, J M

2011-08-01

We report the case of a 36-year old pregnant woman with a Kell alloimmunization (anti-K1), probably secondary to a previous blood transfusion, and a severe hemolytic disease of the fetus. Once the first fetal blood transfusion by cordocentesis was performed, we started treatment with repeated plasmapheresis to maintain anti-K1 titer below 1:32. With this scheme we did not need to perform a second intrauterine fetal blood transfusion and only mild anemia was found in the newborn. Taking into account that the rate of serious complications with plasmapheresis is lower than that related with intrauterine blood transfusion, this could be an alternative approach to repeated transfusions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana.

PubMed

Rivkin, Michael J; Davis, Peter E; Lemaster, Jennifer L; Cabral, Howard J; Warfield, Simon K; Mulkern, Robert V; Robson, Caroline D; Rose-Jacobs, Ruth; Frank, Deborah A

2008-04-01

The objective of this study was to use volumetric MRI to study brain volumes in 10- to 14-year-old children with and without intrauterine exposure to cocaine, alcohol, cigarettes, or marijuana. Volumetric MRI was performed on 35 children (mean age: 12.3 years; 14 with intrauterine exposure to cocaine, 21 with no intrauterine exposure to cocaine) to determine the effect of prenatal drug exposure on volumes of cortical gray matter; white matter; subcortical gray matter; cerebrospinal fluid; and total parenchymal volume. Head circumference was also obtained. Analyses of each individual substance were adjusted for demographic characteristics and the remaining 3 prenatal substance exposures. Regression analyses adjusted for demographic characteristics showed that children with intrauterine exposure to cocaine had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than comparison children. After adjustment for other prenatal exposures, these volumes remained smaller but lost statistical significance. Similar analyses conducted for prenatal ethanol exposure adjusted for demographics showed significant reduction in mean cortical gray matter; total parenchymal volumes; and head circumference, which remained smaller but lost statistical significance after adjustment for the remaining 3 exposures. Notably, prenatal cigarette exposure was associated with significant reductions in cortical gray matter and total parenchymal volumes and head circumference after adjustment for demographics that retained marginal significance after adjustment for the other 3 exposures. Finally, as the number of exposures to prenatal substances grew, cortical gray matter and total parenchymal volumes and head circumference declined significantly with smallest measures found among children exposed to all 4. CONCLUSIONS; These data suggest that intrauterine exposures to cocaine, alcohol, and cigarettes are individually related to reduced head

Pigmented well-differentiated hepatocellular neoplasm with beta-catenin mutation.

PubMed

Souza, Lara Neves; de Martino, Rodrigo Bronze; Thompson, Richard; Strautnieks, Sandra; Heaton, Nigel D; Quaglia, Alberto

2015-12-01

According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the beta-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcinomas. We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver. The patient was a 48-year-old woman, who was asymptomatic, and had a clinical history of intra-uterine exposure to diethylstilbestrol, previous cancers and past oral contraceptive use. The recently proposed term "well-differentiated hepatocellular neoplasm of uncertain malignant potential" should be applied in such cases to highlight the different pathogenesis and risk of malignancy compared to the typical adenomas, and to suggest a careful and customized clinical management.

Normal ultrasonic fetal growth ratios evaluated in cases of fetal disproportion.

PubMed

Crang-Svalenius, E; Jörgensen, C

1991-02-01

During a 2-year period, 5476 normal routine obstetrical ultrasound investigations were performed in the 2nd trimester (16th to 20th week). Data on biparietal diameter (BPD), abdominal diameter (AD) and femur length (FL) have been obtained from this material. Ratios between BPD/AD and BPD/FL have been calculated, and from these ratios, graphs were constructed. Only nine normal fetuses (0.2%) were found to be outside mean +/- 3 SD, and none of the normal cases were +/- 4 SD, so this is perhaps a better guideline for those warranting further investigation. To evaluate if these ratios could better reflect disproportional fetal growth, three cases of triploidy and four cases of dwarfism were tested against these ratios. Triploidy was obvious on the BPD/AD graph and dwarfism on the BPD/FL graph. The ratios were not found to be conclusive in the intrauterine diagnosis of trisomy 21 or of trisomy 18, as only 4 of 17 cases were obvious on the graphs.

Serum cholesterol acceptor capacity in intrauterine growth restricted fetuses.

PubMed

Pecks, Ulrich; Rath, Werner; Bauerschlag, Dirk O; Maass, Nicolai; Orlikowsky, Thorsten; Mohaupt, Markus G; Escher, Geneviève

2017-10-26

Intrauterine growth restriction (IUGR) is an independent risk factor for the development of cardiovascular diseases later in life. The mechanisms whereby slowed intrauterine growth confers vascular risk are not clearly established. In general, a disturbed cholesterol efflux has been linked to atherosclerosis. The capacity of serum to accept cholesterol has been repeatedly evaluated in clinical studies by the use of macrophage-based cholesterol efflux assays and, if disturbed, precedes atherosclerotic diseases years before the clinical diagnosis. We now hypothesized that circulating cholesterol acceptors in IUGR sera specifically interfere with cholesterol transport mechanisms leading to diminished cholesterol efflux. RAW264.7 cells were used to determine efflux of [3H]-cholesterol in response to [umbilical cord serum (IUGR), n=20; controls (CTRL), n=20]. Cholesterol efflux was lower in IUGR as compared to controls [controls: mean 7.7% fractional [3H]-cholesterol efflux, standard deviation (SD)=0.98; IUGR: mean 6.3%, SD=0.79; P<0.0001]. Values strongly correlated to HDL (ρ=0.655, P<0.0001) and apoE (ρ=0.510, P=0.0008), and mildly to apoA1 (ρ=0.3926, P=0.0122) concentrations. Reduced cholesterol efflux in IUGR could account for the enhanced risk of developing cardiovascular diseases later in life.

Decidual vascular changes in early pregnancy as a marker for intrauterine pregnancy.

PubMed

Lichtig, C; Korat, A; Deutch, M; Brandes, J M

1988-09-01

Endometrial vascular changes similar to atherosclerosis of toxemia of pregnancy were described and graded in 217 consecutive endometrial biopsies of known early intrauterine pregnancy. Severe vascular changes were found in 23.5% of cases. Control material consisting of endometrial biopsies of patients with known cases of tubal ectopic pregnancy and various non-pregnancy menstrual disorders showed minimal or no changes except in one case. A parallel study of Aria-Stella phenomenon in 110 cases of uterine pregnancy showed significant changes in only 3.6% of patients. It is obvious that in these cases of positive Arias-Stella findings, the possibility of an extrauterine pregnancy could not be discarded on histologic grounds alone. The authors suggest the use of the vascular changes of the more severe histologic degree as described in this article as a positive or strongly suspicious marker for intrauterine pregnancy whenever this is needed.

Neuropsychological development in preschool children born with asymmetrical intrauterine growth restriction and impact of postnatal head growth.

PubMed

Klaric, Andrea Simić; Galić, Slavka; Kolundzić, Zdravko; Bosnjak, Vlatka Mejaski

2013-07-01

Neuropsychological development and the impact of postnatal head growth were studied in preschool children with asymmetrical intrauterine growth restriction. Examinees born at term with a birth weight below the 10th percentile were matched to the control group according to chronological and gestational age, gender, and maternal education. Fifty children were in each group, with a mean age of 6 years, 4 months. The Touwen neurological examination, the Čuturić developmental test, an imitative hand positions test, and a visual attention test were performed. There were significant differences (P< .03) in motor variables, the developmental quotient, and the imitative hand positions test. Fine motor skills had the most discriminative power. Relative growth of the head in relation to weight gain was positively correlated to neurocognitive outcome. Intrauterine growth-restricted children with a current head circumference ≤10th percentile had poorer outcomes. Conclusively, intrauterine growth restriction has a negative impact on neurocognitive development. Slow postnatal head growth is correlated with a poorer neuropsychological outcome.

Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice.

PubMed

Silva, Jamile R; Ferreira, Lício F A A; Oliveira, Percíllia V S; Nunes, Ivanéia V; Pereira, Ítalo S; Timenetsky, Jorge; Marques, Lucas M; Figueiredo, Tiana B; Silva, Robson A A

2016-01-01

Ureaplasma diversum is an opportunistic pathogen associated with uterine inflammation, impaired embryo implantation, infertility, abortions, premature birth of calves and neonatal pneumonia in cattle. It has been suggested that the intra-uterine infection by Ureaplasma diversum can cause vascular changes that hinder the success of pregnancy. Thus, the aim of this study was to evaluate the changes of intrauterine site of A/J mice in estrus or proestrus phase inoculated with Ureaplasma diversum. The infection was monitored at 24, 48 and 72 hours by the PCR methodology to detect the Ureaplasma in the inoculation site and the profile of circulating blood cells. Morphological changes, intensity of inflammation and the production of cytokines were compared. The infected mice showed local inflammation through the production of IFN-γ and TNF-α. Ureaplasma diversum infections in the reproductive tract of studied mice seemed to be associated with the production of pro-inflammatory cytokines in uterine parenchyma. The levels of TNF-α of infected mice were dependent on the bacterial load of inoculated Ureaplasma. Uterine experimental infections by Ureaplasma diversum have not been mentioned yet and herein we presented the first report of an intrauterine infection model in mice.

Insulin-like growth factor I gene deletion causing intrauterine growth retardation and severe short stature.

PubMed

Woods, K A; Camacho-Hübner, C; Barter, D; Clark, A J; Savage, M O

1997-11-01

The first human case of a homozygous molecular defect in the gene encoding insulin-like growth factor I (IGF-I) is described. The patient was a 15-year-old boy from a consanguineous pedigree who presented with severe intrauterine growth failure, sensorineural deafness and mild mental retardation. Endocrine evaluation of the growth hormone (GH)--IGF-I axis revealed elevated GH secretion, undetectable serum IGF-I and normal serum IGF-binding protein-3, acid-labile subunit, and GH-binding activity. Analysis of the IGF-I gene revealed a homozygous partial IGF-I gene deletion involving exons 4 and 5, which encodes a severely truncated mature IGF-I peptide. This patient demonstrates that complete disruption of the IGF-I gene in man is compatible with life, and indicates a major role for IGF-I in human fetal growth. In addition, his neurological abnormalities suggest that IGF-I may be involved in central nervous system development.

Comparative transcriptomic analyses of normal and malformed flowers in sugar apple (Annona squamosa L.) to identify the differential expressed genes between normal and malformed flowers.

PubMed

Liu, Kaidong; Li, Haili; Li, Weijin; Zhong, Jundi; Chen, Yan; Shen, Chenjia; Yuan, Changchun

2017-10-23

Sugar apple (Annona squamosa L.), a popular fruit with high medicinal and nutritional properties, is widely cultivated in tropical South Asia and America. The malformed flower is a major cause for a reduction in production of sugar apple. However, little information is available on the differences between normal and malformed flowers of sugar apple. To gain a comprehensive perspective on the differences between normal and malformed flowers of sugar apple, cDNA libraries from normal and malformation flowers were prepared independently for Illumina sequencing. The data generated a total of 70,189,896 reads that were integrated and assembled into 55,097 unigenes with a mean length of 783 bp. A large number of differentially expressed genes (DEGs) were identified. Among these DEGs, 701 flower development-associated transcript factor encoding genes were included. Furthermore, a large number of flowering- and hormone-related DEGs were also identified, and most of these genes were down-regulated expressed in the malformation flowers. The expression levels of 15 selected genes were validated using quantitative-PCR. The contents of several endogenous hormones were measured. The malformed flowers displayed lower endogenous hormone levels compared to the normal flowers. The expression data as well as hormone levels in our study will serve as a comprehensive resource for investigating the regulation mechanism involved in floral organ development in sugar apple.

The aging mouth: differentiating normal aging from disease.

PubMed

Lamster, Ira B; Asadourian, Lynda; Del Carmen, Tessa; Friedman, Paula K

2016-10-01

Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40 years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antiprogestin-releasing intrauterine devices

PubMed Central

Nayak, NR; Slayden, OD; Mah, K; Chwalisz, K; Brenner, Robert M

2007-01-01

Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists (AP) are known to suppress the endometrium, induce amenorrhea, and inhibit fertility, AP IUDs may provide an effective contraceptive that also controls endometrial bleeding. Here we assessed the effects of empty (blank) vs AP-releasing (ZK 230 211) IUDs on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, progesterone withdrawal bleeding was prevented and estradiol-dependent proliferation was suppressed by the AP IUDs. In sum, AP IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of estradiol on endometrial proliferation as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding. PMID:17531599

Luteal phase support in intrauterine insemination cycles

PubMed Central

Gün, İsmet; Özdamar, Özkan; Yılmaz, Ali

2016-01-01

Intrauterine insemination (IUI) treatment aims to increase the rate of conception by increasing the chances that the maximum number of healthy sperm reach the site of fertilization. IUI with controlled ovarian stimulation is frequently used in assisted reproduction practice. Although widely used, the efficacy of luteal support in IUI remains controversial. In this article, we aimed to review what we know regarding luteal support in IUI cycles and to adjudicate about the clinical use and benefits of this treatment. Based on the study results available in the literature, it appears to be beneficial to supplement the luteal phase in gonadotropin-stimulated IUI cycles that yield more than one follicle. PMID:28913099

Brain ultrasound findings in neonates treated with intrauterine transfusion for fetal anaemia.

PubMed

Leijser, Lara M; Vos, Nikki; Walther, Frans J; van Wezel-Meijler, Gerda

2012-09-01

The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce. To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome. Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability). A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome. Neonates undergoing IUT for fetal anaemia are at high risk of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differential expression of utrophin-A and -B promoters in the central nervous system (CNS) of normal and dystrophic mdx mice.

PubMed

Baby, Santhosh M; Bogdanovich, Sasha; Willmann, Gabriel; Basu, Utpal; Lozynska, Olga; Khurana, Tejvir S

2010-03-01

Utrophin (Utrn) is the autosomal homolog of dystrophin, the Duchene Muscular Dystrophy (DMD) locus product and of therapeutic interest, as its overexpression can compensate dystrophin's absence. Utrn is transcribed by Utrn-A and -B promoters with mRNAs differing at their 5' ends. However, previous central nervous system (CNS) studies used C-terminal antibodies recognizing both isoforms. As this distinction may impact upregulation strategies, we generated Utrn-A and -B promoter-specific antibodies, Taqman Polymerase chain reaction (PCR)-based absolute copy number assays, and luciferase-reporter constructs to study CNS of normal and dystrophic mdx mice. Differential expression of Utrn-A and -B was noted in microdissected and capillary-enriched fractions. At the protein level, Utrn-B was predominantly expressed in vasculature and ependymal lining, whereas Utrn-A was expressed in neurons, astrocytes, choroid plexus and pia mater. mRNA quantification demonstrated matching patterns of differential expression; however, transcription-translation mismatch was noted for Utrn-B in caudal brain regions. Utrn-A and Utrn-B proteins were significantly upregulated in olfactory bulb and cerebellum of mdx brain. Differential promoter activity, mRNA and protein expressions were studied in cultured C2C12, bEnd3, neurons and astrocytes. Promoter activity ranking for Utrn-A and -B was neurons > astrocytes > C2C12 > bEnd3 and bEnd3 > astrocytes > neurons > C2C12, respectively. Our results identify promoter usage patterns for therapeutic targeting and define promoter-specific differential distribution of Utrn isoforms in normal and dystrophic CNS.

Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction

PubMed Central

Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit; Barzilai, Nir; Greally, John M.

2010-01-01

Background Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. PMID:20126273

Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, K.; Chubb, C.; Huberman, E.

High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteinsmore » were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.« less

Differential entry of ricin into malignant and normal rat hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Decastel, M.; Haentjens, G.; Aubery, M.

1989-02-01

The authors have compared the mechanisms of ricin binding to and entry into Zajdela hepatoma cells (ZHC) and normal rat hepatocytes (HyC). Lactose but not mannan was found to inhibit ricin binding to and toxicity on ZHC and HyC. This finding suggests that ricin binding, entry, and toxicity are expressed only through the galactose binding sites on ZHC and HyC. Nevertheless, the characteristics of ricin binding and its entry pathway appeared to be different in several respects in ZHC and HyC. Scatchard analysis of equilibrium data determined over a wide range of {sup 125}I-labeled ricin concentrations yielded a curvilinear plotmore » for ZHC, while a straight line was obtained for HyC. These results indicate that only ZHC possess high-affinity receptors for ricin. Analysis of ricin toxicity of ZHC and HyC, in the presence of ammonium chloride or after K{sup +}-depletion in both cell types, suggests that the ricin bound to galactose receptors entered through neutral vesicles in ZHC, and through both neutral and acidic vesicles in HyC. The qualitative and quantitative differences found between the process of receptor-mediated endocytosis of ricin in ZHC and HyC might explain the differential sensitivity of the two cell types toward the toxin.« less

Review on intrauterine programming: Consequences in rodent models of mild diabetes and mild fat overfeeding are not mild.

PubMed

Jawerbaum, A; White, V

2017-04-01

An adverse intrauterine programming occurs in diabetes and obesity as the consequence of an adverse maternal environment that affects the appropriate fetoplacental development and growth. Experimental models of diabetes and fat overfeeding have provided relevant tools to address putative mechanisms of the adverse intrauterine programming. The current knowledge far extends from the original thoughts of the resulting intrauterine programming of metabolic and cardiovascular diseases to a full range of alterations that affect multiple tissues, organs, and systems that will compromise the long-life health of the offspring. This review examines the postnatal effects of rodent models of mild diabetes and fat overfeeding, identifying the multiple organ derangements in the offspring resulting from mild maternal adverse conditions. In addition, the comparison of experimental models of severe diabetes and fat overfeeding and the crucial role of the placenta are discussed, providing an update of the actual scenario of the putative mechanisms and adverse consequences of maternal metabolic derangements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of pregnancy rates between patients with and without local endometrial scratching before intrauterine insemination.

PubMed

Senocak, G C; Yapca, O E; Borekci, B

2017-11-01

To determine the implantation success of local endometrial injury in patients undergoing intrauterine insemination following ovulation induction with gonadotropins as an infertility treatment. In this prospective randomized controlled trial, ovulation induction was performed with gonadotropins in 80 patients following intrauterine insemination. In 40 patients, local endometrial injury (scratch) was performed in the midluteal phase of the cycle preceding ovarian stimulation with a Novak curette to the posterior side of the endometrial cavity. Fifteen pregnancies (37.5%) and 11 clinical pregnancies (27.5%) occurred in the intervention group, whereas eight pregnancies (20%) and five clinical pregnancies (12.5%) occurred in the control group. Although the pregnancy rates and clinical pregnancy rates were increased in the intervention group, no statistically significant difference was found between the intervention and control groups (pregnancy rates: P=0.084; clinical pregnancy rates: P=0.094). Performing local endometrial injury (scratch) in the cycle preceding ovulation induction in patients with a diagnosis of infertility and indication for intrauterine insemination increased the pregnancy and clinical pregnancy rates. This increase was not, however, statistically significant. More randomized, controlled, prospective studies with larger patient numbers are required before the use of iatrogenic induction of local endometrial injury can be recommended in routine clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Levonorgestrel-releasing intrauterine system placement for severe uterine cervical stenosis after conization: two case reports.

PubMed

Motegi, Emi; Hasegawa, Kiyoshi; Kawai, Satoshi; Kiuchi, Kaori; Kosaka, Nobuaki; Mochizuki, Yoshiko; Fukasawa, Ichio

2016-03-09

Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully. We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic. To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.

Levonorgestrel-releasing intrauterine system use in premenopausal women with symptomatic uterine leiomyoma: a systematic review.

PubMed

Jiang, Wenxiao; Shen, Qi; Chen, Miaomiao; Wang, Ying; Zhou, Qingfeng; Zhu, Xuejie; Zhu, Xueqiong

2014-08-01

A systematic review is done to determine the efficacy and safety of levonorgestrel-releasing intrauterine systems as a treatment using in premenopausal women with symptomatic uterine leiomyoma. We searched the Medline, Central and ICTRP databases for all articles published from inception through July 2013 that examined the following outcomes: uterine volume, uterine leiomyoma volume, endometrial thickness, then menstrual blood loss, blood haemoglobin, ferritin and hematocrit levels, treatment failure rate, device expulsion rate, hysterectomy rate and side effects. From 645 studies, a total of 11 studies met our inclusion criteria with sample sizes ranging from 10 to 104. Evidence suggested that levonorgestrel-releasing intrauterine systems could decrease uterine volume and endometrial thickness, significantly reduce menstrual blood loss, and increase blood haemoglobin, ferritin and hematocrit levels. There was no evidence for decreasing uterine leiomyoma volume. There were no adverse effects on the ovarian function except for ovarian cysts. Device expulsion rates were low, which associated with leiomyoma size (larger than 3cm) but not with leiomyoma location. Irregular bleeding/spotting was observed at the beginning of the follow-up period and then decreased progressively. Results of this systematic review indicate that levonorgestrel-releasing intrauterine systems may be effective and safe treatment for symptomatic uterine leiomyoma in premenopausal women. Copyright © 2014 Elsevier Inc. All rights reserved.

Intrauterine diagnosis and management of fetal goiter: a case report.

PubMed

Koyuncu, Faik Mumtaz; Tamay, Aslı Goker; Bugday, Sultan

2010-01-01

Fetal goiter can be the result of maternal hyperthyroidism treated with antithyroid drugs. Polyhydramnios may be the presenting symptom and can be diagnosed prenatally by sonography. We report a case of fetal goiter diagnosed at 30 weeks of gestation and fetal hypothyroidism confirmed by cordocentesis. Intra-amniotic levothyroxine was administered. Onset of preterm labor could not be prevented. The risks and benefits of intrauterine treatment of fetal goitrous hypothyroidism are discussed.

Size evolution of ultrafine particles: Differential signatures of normal and episodic events.

PubMed

Joshi, Manish; Khan, Arshad; Anand, S; Sapra, B K

2016-01-01

The effect of fireworks on the aerosol number characteristics of atmosphere was studied for an urban mega city. Measurements were made at 50 m height to assess the local changes around the festival days. Apart from the increase in total number concentration and characteristic accumulation mode, short-term increase of ultrafine particle concentration was noted. Total number concentration varies an order of magnitude during the measurement period in which peak occurs at a frequency of approximately one per day. On integral scale, it seems not possible to distinguish an episodic (e.g. firework bursting induced aerosol emission) and a normal (ambient atmospheric changes) event. However these events could be differentiated on the basis of size evolution analysis around number concentration peaks. The results are discussed relative to past studies and inferences are drawn towards aerosol signatures of firework bursting. The short-term burst in ultrafine particle concentration can pose an inhalation hazard. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study.

PubMed

Chen, Yi-Jen; Hsu, Teh-Fu; Huang, Ben-Shian; Tsai, Hsiao-Wen; Chang, Yen-Hou; Wang, Peng-Hui

2017-06-01

According to 3 randomized trials, the levonorgestrel-releasing intrauterine system significantly reduced recurrent endometriosis-related pelvic pain at postoperative year 1. Only a few studies have evaluated the long-term effectiveness of the device for preventing endometrioma recurrence, and the effects of a levonorgestrel-releasing intrauterine system as a maintenance therapy remain unclear. The objective of the study was to evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing postoperative endometrioma recurrence. From May 2011 through March 2012, a randomized controlled trial including 80 patients with endometriomas undergoing laparoscopic cystectomy followed by six cycles of gonadotropin-releasing hormone agonist treatment was conducted. After surgery, the patients were randomized to groups that did or did not receive a levonorgestrel-releasing intrauterine system (intervention group, n = 40, vs control group, n = 40). The primary outcome was endometrioma recurrence 30 months after surgery. The secondary outcomes included dysmenorrhea, CA125 levels, noncyclic pelvic pain, and side effects. Endometrioma recurrence at 30 months did not significantly differ between the 2 groups (the intervention group, 10 of 40, 25% vs the control group 15 of 40, 37.5%; hazard ratio, 0.60, 95% confidence interval, 0.27-1.33, P = .209). The intervention group exhibited a lower dysmenorrhea recurrence rate, with an estimated hazard ratio of 0.32 (95% confidence interval, 0.12-0.83, P = .019). Over a 30 month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a visual analog scale score (mean ± SD, 60.8 ± 25.5 vs 38.7 ± 25.9, P < .001, 95% confidence interval, 10.7-33.5), noncyclic pelvic pain visual analog scale score (39.1 ± 10.9 vs 30.1 ± 14.7, P = .014, 95% confidence interval, 1.9-16.1), and CA125 (median [interquartile range], -32.1 [-59.1 to 14.9], vs -15.6 [-33.0 to 5

Care quality following intrauterine death in Spanish hospitals: results from an online survey.

PubMed

Cassidy, Paul Richard

2018-01-10

The objective of the study was to evaluate practices in Spanish hospitals after intrauterine death in terms of medical/ technical care and bereavement support care. A cross-sectional descriptive study using an online self-completion questionnaire. The population was defined as women who had experienced an intrauterine fetal death between sixteen weeks and birth, either through spontaneous late miscarriage/stillbirth or termination of pregnancy for medical reasons. Respondents were recruited through an online advertisement on a stillbirth charity website and social media. The analysis used Pearson's chi-squared (p ≤ 0.05) test of independence to cross-analyse for associations between objective measures of care quality and independent variables. Responses from 796 women were analysed. Half of the women (52.9%) had postmortem contact with their baby. 30.4% left the hospital with a least one linking object or a photograph. In 35.8% of cases parents weren't given any option to recover the body/remains. 22.9% of births ≥26 weeks gestation were by caesarean, with a significant (p < 0.001) difference between public hospitals (16.8%) and private hospitals (41.5%). 29.3% of respondents were not accompanied during the delivery. 48.0% of respondents recalled being administered sedatives at least once during the hospital stay. The autopsy rate in stillbirth cases (≥ 20 weeks) was 70.5% and 44.4% in cases of termination of pregnancy (all gestational ages). Consistent significant (p < 0.05) differences in care practices were found based on gestational age and type of hospital (public or private), but not to other variables related to socio-demographics, pregnancy history or details of the loss/death. Intrauterine deaths at earlier gestational ages received poorer quality care. Supportive healthcare following intrauterine death is important to women's experiences in the hospital and beneficial to the grief process. Many care practices that are standard in

Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.

PubMed Central

Knox, J. D.; Cress, A. E.; Clark, V.; Manriquez, L.; Affinito, K. S.; Dalkin, B. L.; Nagle, R. B.

1994-01-01

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression. Images Figure 1 Figure 2 Figure 3 PMID:8030747

Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling.

PubMed

Tao, Ling; Park, Jong-Yung; Lambert, Joshua D

2015-02-01

We have previously reported that the green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), can induce oxidative stress in oral cancer cells but exerts antioxidant effects in normal cells. Here, we report that these differential prooxidative effects are associated with sirtuin 3 (SIRT3), an important mitochondrial redox modulator. EGCG rapidly induced mitochondria-localized reactive oxygen species in human oral squamous carcinoma cells (SCC-25, SCC-9) and premalignant leukoplakia cells (MSK-Leuk1), but not in normal human gingival fibroblast cells (HGF-1). EGCG suppressed SIRT3 mRNA and protein expression, as well as, SIRT3 activity in SCC-25 cells, whereas it increased SIRT3 activity in HGF-1 cells. EGCG selectively decreased the nuclear localization of the estrogen-related receptor α (ERRα), the transcription factor regulating SIRT3 expression, in SCC-25 cells. This indicates that EGCG may regulate SIRT3 transcription in oral cancer cells via ERRα. EGCG also differentially modulated the mRNA expressions of SIRT3-associated downstream targets including glutathione peroxidase 1 and superoxide dismutase 2 in normal and oral cancer cells. SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells. Our results provide new biomarkers to be further explored in animal studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[DENTAL STATUS OF PATIENTS WITH INTRAUTERINE GROWTH RESTRICTION IN PAST HISTORY DURING PERIOD OF REMOVABLE AND PERMANENT DENTITION].

PubMed

Garmash, O V; Ryabokon, E N

2014-12-01

The analysis of the dental status in patients with IUGR in past history in period of removable and permanent dentition was conducted. 39 patients with intrauterine growth retardation in past history were examined. The clinical, statistical methods were held. Concluded that the child, who was born with IUGR, later in future life, has a great risk of dental diseases. The most considerable violations were found in patients with "symmetrical" form of intrauterine growth retardation. It is proposed to use clinical markers as possible predictors of periodontal diseases.

Continuation of a Levonorgestrel Intrauterine Device During Hematopoietic Stem Cell Transplant: A Case Report.

PubMed

Brady, Paula C; Soiffer, Robert J; Ginsburg, Elizabeth S

2017-04-01

During treatment of hematologic malignancies in premenopausal women, both menstrual suppression and contraception are crucial. Continuation of hormonal intrauterine devices (IUDs) - widely used and highly effective contraceptives that also decrease menstrual flow - is controversial during hematopoietic stem cell transplants (SCTs) due to infectious and vaginal bleeding concerns. A 23-year-old nulligravid female was diagnosed with acute myeloid leukemia (AML, positive for FLT3-ITD, DNMT3A and RUNX1, with normal cytogenetics). She elected to retain her existing levonorgestrel-containing IUD during chemotherapy and SCT. During and following treatment, she remained amenorrheic without infection, despite severe neutropenia and thrombocytopenia. Eight months later, she remains in remission without IUD-related complications. This is the first report of levonorgestrel IUD retention during hematopoietic SCT. Despite severe neutropenia and thrombocytopenia, the patient developed neither pelvic infection by retaining her IUD nor significant vaginal bleeding. Future studies are needed to confirm the safety of levonorgestrel IUDs in women undergoing SCT. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

In vivo measurement of intrauterine pressure by telemetry: a new approach for studying parturition in mouse models

PubMed Central

Pierce, Stephanie L.; Kutschke, William; Cabeza, Rafael

2010-01-01

Transgenic and knockout mouse models have proven useful in the study of genes necessary for parturition—including genes that affect the timing and/or progression of labor contractions. However, taking full advantage of these models will require a detailed characterization of the contractile patterns in the mouse uterus. Currently the best methodology for this has been measurement of isometric tension in isolated muscle strips in vitro. However, this methodology does not provide a real-time measure of changes in uterine pressure over the course of pregnancy. Recent advances have opened the possibility of using radiotelemetric devices to more accurately and comprehensively study intrauterine pressure in vivo. We tested the effectiveness of this technology in the mouse, in both wild-type (WT) mice and a mouse model of defective parturition (SK3 channel-overexpressing mice), after surgical implant of telemetry transmitters into the uterine horn. Continuous recordings from day 18 of pregnancy through delivery revealed that WT mice typically deliver during the 12-h dark cycle after 19.5 days postcoitum. In these mice, intrauterine pressure gradually increases during this cycle, to threefold greater than that measured during the 12-h cycle before delivery. SK3-overexpressing mice, by contrast, exhibited lower intrauterine pressure over the same period. These results are consistent with the outcome of previous in vitro studies, and they indicate that telemetry is an accurate method for measuring uterine contraction, and hence parturition, in mice. The use of this technology will lead to important novel insights into changes in intrauterine pressure during the course of pregnancy. PMID:20460604

Effects of Intrauterine Devices in Mares: A Histomorphological and Immunohistochemical Evaluation of the Endometrium.

PubMed

Klein, V; Müller, K; Schoon, H A; Reilas, T; Rivera del Alamo, M M; Katila, T

2016-02-01

Oestrous suppression by intrauterine devices (IUDs) is caused by prolongation of luteal function, but the biological mechanism is unknown. The aim of the study was to investigate mechanisms which could explain the action of IUDs. Thirty mares were age-matched and either inseminated (AI, n = 15) or fitted with an IUD (IUD, n = 15) and subsequently divided into four groups: AI-P, pregnant (n = 8); AI-N, non-pregnant (n = 7); IUD-P, prolonged luteal phase (n = 7); and IUD-N, normal luteal phase (n = 8). The median ages were 5.5 and 7 years in AI-P and IUD-P groups and 14 and 11 years in AI-N and IUD-N groups, respectively. On Day 15 after ovulation, an endometrial biopsy was obtained to study histomorphological and immunohistochemical expression patterns of uterine proteins (uteroferrin, UF; uterocalin, UC; uteroglobin, UG), oestrogen and progesterone receptors (ER, PR), proliferation marker Ki-67 and content of inflammatory cells. Expression of UF was higher in IUD mares; the difference between pregnant and IUD-P mares was significant. Mares exhibiting a prolonged luteal phase (AI-P, IUD-P) showed only mild angiosclerosis and lower expression of both ER and PR than mares with a normal luteal phase (AI-N, IUD-N). No significant differences were detected in the numbers of inflammatory cells, with the exception of macrophages, which were more numerous in AI-P than AI-N mares. Although inflammatory cells were not detected in IUD mares, increased UF levels may indicate chronic inflammation. Young age and normality of the endometrial blood vessels may improve the efficacy of IUDs. © 2015 Blackwell Verlag GmbH.

Problematic Substance Use in Urban Adolescents: Role of Intrauterine Exposures to Cocaine and Marijuana and Post-Natal Environment

PubMed Central

Frank, Deborah A.; Kuranz, Seth; Appugliese, Danielle; Cabral, Howard; Chen, Clara; Crooks, Denise; Heeren, Timothy; Liebschutz, Jane; Richardson, Mark; Rose-Jacobs, Ruth

2014-01-01

Background Linkages between intrauterine exposures to cocaine and marijuana and adolescents’ problematic substance use have not been fully delineated. Methods Prospective longitudinal study with assessors unaware of intrauterine exposure history followed 157 urban participants from birth until late adolescence. Level of intrauterine exposures was identified by mother's report and infant’s meconium. Problematic substance use, identified by the Voice Diagnostic Interview Schedule for Children (V-DISC) or the Audio Computer Assisted Self-Interview (ACASI) and urine assay, was a composite encompassing DSM-IV indication of tolerance, abuse, and dependence on alcohol, marijuana, and tobacco and any use of cocaine, glue, or opiates. Results Twenty percent (32/157) of the sample experienced problematic substance use by age 18 years, of whom the majority (22/157) acknowledged abuse, tolerance or dependence on marijuana with or without other substances. Structural equation models examining direct and indirect pathways linking a Cox survival model for early substance initiation to a logistic regression models found effects of post-natal factors including childhood exposure to violence and household substance use, early youth substance initiation, and ongoing youth violence exposure contributing to adolescent problematic substance use. Conclusion We did not identify direct relationships between intrauterine cocaine or marijuana exposure and problematic substance use, but did find potentially modifiable post-natal risk factors also noted to be associated with problematic substance use in the general population including earlier substance initiation, exposure to violence and to household substance use. PMID:24999059

Clinical characteristics and reproductive outcome following hysteroscopic adhesiolysis of patients with intrauterine adhesion--a retrospective study.

PubMed

Liu, Xin; Duan, Hua; Wang, Yongjun

2014-01-01

The authors performed a retrospective clinical analysis of 153 patients with intrauterine ashesion (IUA) who underwent hysteroscopic adhesiolysis. A follow-up office hysteroscopy was performed in all cases after three months. On follow-up hysteroscopy, 22 patients showed reformation of adhesions and required a repeat procedure. The primary risk factor for IUA was uterine curettage associated with pregnancy termination. The follow-up study revealed that the rate of pregnancy after IUA treatment was 51%. The conception rate in women who had reformation of IUA was significantly lower than that of women who had a normal cavity following adhesiolysis. Therefore the authors conclude that prevention is more important than therapy in IUA. Increasing education about avoiding curettage is necessary to reduce the incidence of IUA. Outreach is particularly important for older women with less education. However, hysteroscopic adhesiolysis for IUA is a safe and effective method of choice for restoring menstrual function and fertility.

Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

PubMed Central

Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

2015-01-01

The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting. PMID:26068810

Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

NASA Astrophysics Data System (ADS)

Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

2015-06-01

The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.

Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells.

PubMed

Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

2015-06-12

The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.

A monocrystal graphene domain biosensor array with differential output for real-time monitoring of glucose and normal saline.

PubMed

Shi, Junjie; Li, Xin; Chen, Qian; Gao, Kun; Song, Hui; Guo, Shixi; Li, Quanfu; Fang, Ming; Liu, Weihua; Liu, Hongzhong; Wang, Xiaoli

2015-05-07

A biosensor array with differential output based on a monocrystal graphene domain is proposed to realize high resolution measurements. The differential output structure can eliminate the noise that comes from graphene crystal orientation and grain boundary, as well as the fluctuation that comes from the contact resistance and experiment process, so as to improve resolution in the lower concentration. We have fabricated a high quality monocrystal graphene domain that has millimeter size by the chemical vapor deposition method. Two identical graphene ribbons that are cut from the same domain are used as field effect transistor source-to-drain channels for the reference and the test of differential output, respectively. The experimental results show that the source-to-drain current has a fast response shorter than 0.5 second in glucose, normal saline and pH buffer solutions of different concentrations. Sensitivity increases exponentially with the increase of concentration of the tested liquid and the high resolution range is 0.01-2 wt% in glucose and 0.0009-0.018 wt% in saline, and the highest resolutions of glucose and saline are 0.01 wt% and 0.0009 wt%, respectively. We have fabricated a 1 × 4 array structure with differential outputs that pave the way for rapidly detecting ultra-low concentration of analytes.

Intrauterine insemination versus timed intercourse with clomiphene citrate in polycystic ovary syndrome: a randomized controlled trial.

PubMed

Abu Hashim, Hatem; Ombar, Osama; Abd Elaal, Ibrahim

2011-04-01

To compare the efficacy of intrauterine insemination vs. timed intercourse with clomiphene citrate as a first-line treatment for anovulatory infertility associated with polycystic ovary syndrome. A randomized controlled trial following the CONSORT criteria. A university hospital and a private practice setting. 188 women (525 cycles) with polycystic ovary syndrome. Women received three consecutive cycles of ovulation induction with clomiphene citrate and intrauterine insemination (n=93, 259 cycles) or three consecutive cycles of clomiphene citrate with timed intercourse (n=95, 266 cycles). Clinical pregnancy rate per cycle, number of growing and mature follicles, serum estradiol, endometrial thickness at the hCG day, serum progesterone, ovulation, miscarriage and live birth rates. There were no differences between the two groups regarding the clinical pregnancy rate per cycle or per woman (8.49 vs. 7.89% and 23.6 vs. 22.1%; p=0.26 and p=0.33, respectively). Two twin pregnancies occurred in each group. Miscarriage and live birth rates were comparable (18.1 vs. 19% and 19.35 vs. 17.89%; p=0.31 and p=0.33, respectively). No ectopic, higher-order pregnancies or cases of ovarian hyperstimulation syndrome occurred. No differences were found regarding the number of follicles, serum progesterone, ovulation rates, estradiol levels or endometrial thickness at the hCG day (7.7±0.4 vs. 7.5±0.6mm; p=0.54). Ovulation induction with clomiphene citrate and timed intercourse is as effective as that with intrauterine insemination for achieving pregnancy in polycystic ovary syndrome and could represent the initial treatment option, being less invasive and less expensive than intrauterine insemination. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

The differential diagnosis of acute pericarditis from the normal variant: new electrocardiographic criteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ginzton, L.E.; Laks, M.M.

1982-05-01

We examined the quantitative electrocardiographic differentiation of acute pericarditis from normal variant ST/T changes. The ECGs of 19 patients with acute pericarditis were compared with those of 20 subjects with typical normal variant changes. Patients were excluded if their ECGs demonstrated conditions that markedly altered repolarization. The positive predictive values (PPV) and negative predictive values (NPV) of previously reported criteria were not high (PPV = 0.54 - 0.83, NPV = 0.56 - 0.58). In contrast, in the present study, a T-wave amplitude in lead V/sub 6/ of less than or equal to 0.3 mV diagnosed acute pericarditis (p < 0.005,more » PPV = 0.85, NPV = 0.85), but there was overlap of patients between the groups. The ratio of the amplitude of the onset of the ST segment of the amplitude of the T wave in that lead (ST/T ratio in V/sub 6/) proved to be the most reliable discriminator. An ST/T ratio greater than or equal to 0.25 diagnosed all patients with acute pericarditis (p less than or equal to 0.005, PPV = 1.0, NPV = 1.0). The ST/T ratio greater than or equal to 0.25 in V/sub 4/, V/sub 5/ (both p < 0.005, PPV = 0.87, NPV = 1.0) and I (p less than or equal to 0.005, PPV = 0.80, NPV = 0.81) were also significant discriminators. Thus, if V/sub 6/ is unavailable, an ST/T ratio greater than or equal to 0.25 in V/sub 5/, V/sub 4/ or I is highly suggestive of acute pericarditis. An ST/T ratio greater than or equal to 0.25 in V/sub 6/ discriminated the ECGs of all patients with acute pericarditis from normal variants in this study.« less

[Intrauterine fetal therapy of NIHF with massive pleural effusion - a case study].

PubMed

Sobczuk, Kamila; Wojtera, Justyna; Celewicz, Zbigniew; Szaflik, Krzysztof

2013-05-01

Hydrops fetalis (fetal hydrops) is a serious fetal condition defined as abnormal accumulation of fluid in two or more extravascular compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Edema is classified as immune or non-immune. Today more than 90% of fetal edema has non-immune cause. This paper presents a case of a pregnant woman who was admitted to the Obstetrics and Gynecology Department because of fetal hydrops with massive pleural effusion and polyhydramnios at 34 weeks gestation. The intrauterine therapy consisted of two treatments. During the first surgery amnioreduction, evacuation of fluid from the pleural cavity of the fetus, and shunts to both pleural cavities were performed. During the second surgery amnioreduction, cordocentesis with albumin administration and pleural shunt were performed. Intrauterine therapy led to a reduction of swelling of the fetus from 7mm up to 1-2 mm and the total evacuation of fluid from the pleural cavity and the fetal lung expansion. We also present the condition of the neonate after birth and after 12 months of life.

Actinomyces-like organisms in cervical smears from women using intrauterine contraceptive devices.

PubMed Central

Duguid, H L; Parratt, D; Traynor, R

1980-01-01

Cervical smears from 293 users of intrauterine contraceptive devices attending family planning clinics in East Fife, Dundee, and Angus were stained by Papanicolaou and Gram's methods and examined for actinomyces-like organisms. Of the 128 women using plastic devices, 40 gave smears positive for these organisms. In contrast only two positive smears were obtained from the 165 women using devices containing copper and none from a control group of 300 women taking oral contraceptives. Colonisation was more common in women whose plastic devices had been in situ for over two years. Correlations between the presence of these organisms and recorded incidences of pain and both clinical and cytological evidence of inflammation of the lower genital tract were highly significant (p = 0.00001, p < 0.00001, and p < 0.00001 respectively). The results suggest that plastic intrauterine contraceptive devices predispose to colonisation by actinomyces-like organisms, particularly after long-term use. Hence if the apparently bacteriostatic action of copper devices is confirmed these should probably be more widely used. Images FIG 1 FIG 2 PMID:7427358

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data.

PubMed

Li, Xiaohong; Brock, Guy N; Rouchka, Eric C; Cooper, Nigel G F; Wu, Dongfeng; O'Toole, Timothy E; Gill, Ryan S; Eteleeb, Abdallah M; O'Brien, Liz; Rai, Shesh N

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data

PubMed Central

Li, Xiaohong; Brock, Guy N.; Rouchka, Eric C.; Cooper, Nigel G. F.; Wu, Dongfeng; O’Toole, Timothy E.; Gill, Ryan S.; Eteleeb, Abdallah M.; O’Brien, Liz

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly

Intrauterine insemination versus fallopian tube sperm perfusion in non-tubal infertility

PubMed Central

Shekhawat, G.S.

2012-01-01

Background Controlled ovarian hyperstimulation (COH) combined with intrauterine insemination (IUI), using a volume of 0.5 ml of inseminate is commonly offered to couples with non-tubal sub fertility. Another method is Fallopian tube sperm perfusion (FSP) which is based on a pressure injection of 4 ml of sperm suspension while attempting to seal the cervix to prevent semen reflux. This technique ensures the presence of higher sperm density in the fallopian tubes at the time of ovulation than standard IUI. The aim of this study was to compare the efficiency of standard intrauterine insemination (IUI) and Fallopian tube sperm perfusion (FSP) in the treatment of non-tubal infertility. Methods 200 consecutive patients with infertility in 404 stimulated cycles were included in the study. Those randomized to standard IUI included 100 patients in 184 cycles [158 clomiphene citrate/human menopausal gonadotrophin cycles and 26 Letrozole/FSH cycles exclusively for polycystic ovarian disease patients] (group A). Patients subjected to FSP included 100 patients in 220 cycles (193 clomiphene citrate/human menopausal gonadotrophin cycles and 27 Letrozole/FSH cycles exclusively for polycystic ovarian disease patients] (group B). Swim up semen preparation technique was used in all cases. Insemination was performed in both groups 34–37 h after hCG administration. Standard IUI was performed using 0.5 ml of inseminate. In FSP 4 ml inseminate was used. Results In group A (184 IUI cycles in 100 patients), 22 clinical pregnancies (presence of gestational sac with fetal cardiac activity) occurred (11.95% per cycle over four cycles). In group B, (220 cycles of FSP in 100 patients), 48 clinical pregnancies occurred (21.81% per cycle over four cycles) and this difference was statistically significant (p < 0.05). Conclusions For non-tubal sub fertility, the results indicate clear benefit for FSP (Fallopian tube sperm perfusion) over IUI (Intrauterine insemination). PMID:24532873

Intrauterine position affects fetal weight and crown-rump length throughout gestation.

PubMed

Jang, Y D; Ma, Y L; Lindemann, M D

2014-10-01

To investigate the effect of intrauterine positions on fetal growth throughout gestation, data from a total of 65 gilts (n = 784 fetuses) that were slaughtered at assigned days of gestation (d 43, 58, 73, 91, 101, and 108) on a project to evaluate fetal mineral deposition were used. Placenta units were removed from the uterus, and position, sex, weight, and crown-rump length (CRL) of each fetus were recorded. Fetuses were classified into 5 categories within a uterine horn for the absolute intrauterine position: the ovarian end (OE) of the uterine horn, next to the ovarian end (NOE), the middle (MD), next to the cervical end (NCE), and the cervical end (CE), and also classified for the relative fetal position with respect to the sex of adjacent fetuses. Fetuses at the OE and NOE of the uterine horn tended to be heavier (P = 0.06) and longer (P < 0.05) than those at the MD of the uterine horn at d 58 of gestation. Fetuses at the OE of the uterine horn were also heavier and longer than those at the MD and NCE of the uterine horn at d 101 and 108 of gestation (P < 0.05). Fetuses at the CE of the uterine horn were intermediate in weight and length. There were no major effects of adjacent fetal sex (fetuses surrounded by the opposite sexes) in weight or length. Male fetuses were heavier than female fetuses at d 43, 58, 73, and 108 of gestation (P < 0.05) and longer than female fetuses at d 58 (P = 0.06), 73 (P < 0.05), 101 (P = 0.07), and 108 (P < 0.05) of gestation. Fetal weight was highly correlated with CRL at all gestational ages (P < 0.01). These results indicate that 1) the absolute intrauterine position affects fetal growth more than the sex of the adjacent fetus in the uterine horn, 2) each end of the uterine horn (OE and CE) has heavier fetuses than the MD, and 3) male pigs grow faster than female pigs even before birth.

Intrauterine inflammation, cerebral oxygen consumption and susceptibility to early brain injury in very preterm newborns.

PubMed

Stark, Michael J; Hodyl, Nicolette A; Belegar V, Kiran Kumar; Andersen, Chad C

2016-03-01

In utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine inflammation imposes an elevated cerebral metabolic load and increased fractional oxygen extraction (cFTOE) with cFTOE further increased in the presence of early P/IVH. Eighty-three infants ≤30 weeks gestation were recruited. Exposure to intrauterine inflammation was determined by placental histology. Total internal carotid blood flow (Doppler ultrasound) and near infrared spectroscopy were measured and cerebral oxygen delivery (mcerbDO2), consumption (mcerbVO2) and cFTOE were calculated on days 1 and 3 of life. Primary outcome was defined as death or P/IVH >grade II (cranial sonograph) by day 3. Infants exposed to intrauterine inflammation had higher total internal carotid blood flow (92 vs 63 mL/kg/min) and mcerbDO2 (13.7 vs 10.1 mL/kg/min) than those not exposed to inflammation. Newborns with P/IVH had both higher oxygen consumption and extraction compared with those without sonographic injury regardless of exposure to intrauterine inflammation. Further, in preterms exposed to inflammation, those with P/IVH had higher consumption (6.1 vs 4.8 mL/kg/min) and extraction than those without injury. These differences were observed only on day 1 of life. Although P/IVH is multifactorial in preterm newborns, it is likely that cerebral hypoxic-ischaemia plays a central pathophysiological role. These data provide a mechanistic insight into this process and suggests that the increased cerebral metabolic load imposed by the presence of inflammation results in a higher risk of critical hypoxic ischaemia in the preterm with increased susceptibility to significant P/IVH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Evaluation of Efficacy of Herbal Intrauterine Infusion Uterofix Liquid in Treatment of Various Reproductive Disorders in Cows: A Field Study.

PubMed

Verma, Satinder; Choudhary, Adarsh; Maini, Shivi; Ravikanth, K

2016-01-01

To evaluate the efficacy of herbal intrauterine infusion Uterofix liquid in the treatment of various reproductive disorders in cows. Based on symptoms of endometritis, anestrous, metritis, and repeat breeders, 28 cows were selected to study the efficacy of herbal intrauterine infusion Uterofix liquid (M/S Ayurvet Limited) in uterine infections study. Group T0 (n = 8) cows served as control group, no treatment was given to this group, Group T1 (n = 5) repeat breeder cows, Group T2 (n = 5) endometritis effected cows, Group T3 (n = 5) anoestrus cows, and Group T4 (n = 5) metritis suffered cows were treated with Uterofix liquid (25 ml as intrauterine infusion once a day for 3-5 days). Total observational period was 60 days. Number of treatments needed, nature of discharge in first posttreatment estrus (physical examination), after treatment number of animal showing heat/estrus out of total treated, and posttreatment conception rate were used as criteria to judge the success or failure of treatment. Results revealed that 18 out of 20 animals (90%) showed signs of heat with clear discharge, recovered completely without causing any irritation, or severe irritation/sloughing of genital mucous membrane after Uterofix liquid treatment. Herbal intrauterine infusion Uterofix liquid significantly treated the uterine infections in cows. Uterine infection is a major problem in reproductive management. A wide variety of genital tract diseases of female domestic animals are known to produce significant losses and responsible for poor fertility. Amongst these highly prevalent are metritis and repeat breeding in high-producing dairy cows which if remains untreated are associated with low conception rate per artificial insemination (AI), extended interval to pregnancy, increased culling, and economic losses. As herbal remedy the Uterofix liquid (Ayurvet Limited, India) was highly efficacious as an intrauterine infusion to treat different reproductive disorders.

Environmental Tobacco Smoke Exposure during Intrauterine Period, Promotes Caspase Dependent and Independent DNA Fragmentation in Sertoli-Germ Cells

PubMed Central

Yüksel, Beril; Kilic, Sevtap; Lortlar, Nese; Tasdemir, Nicel; Sertyel, Semra; Bardakci, Yesim; Aksu, Tarik; Batioglu, Sertaç

2014-01-01

Objectives. To investigate the effect of cigarette smoke exposure during intrauterine period on neonatal rat testis. Methods. Twenty-five rats were randomized to be exposed to cigarette smoke with the Walton Smoking Machine or to room air during their pregnancies. The newborn male rats (n = 21) were grouped as group 1 (n = 15) which were exposed to cigarette smoke during intrauterine life and group 2 (n = 6) which were exposed to room air during intrauterine life. The orchiectomy materials were analyzed with TUNEL immunofluorescent staining for detection of DNA damage. To detect apoptosis, immunohistochemical analyses with caspase-3 were performed. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORES); secondary outcomes were Sertoli-cell count and birth-weight of rats. Results. Sertoli cell apoptosis was increased in group 1 (HSCORE = 210.6 ± 41.9) when compared to group 2 (HSCORE = 100.0 ± 17.8) (P = 0.001). Sertoli cell count was decreased in group 1 (P = 0.043). The HSCORE for the germ cells was calculated as 214.0 ± 46.2 in group 1 and 93.3 ± 10.3 in group 2 (P = 0.001) referring to an increased germ cell apoptosis in group 1. The apoptotic indexes for group 1 were 49.6 ± 9.57 and 29.98 ± 2.34 for group 2 (P = 0.001). The immunofluorescent technique demonstrated increased DNA damage in seminiferous epithelium in group 1. Conclusions. Intrauterine exposure to cigarette smoke adversely affects neonatal testicular structuring and diminishes testicular reserve. PMID:25045542

Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: the European Active Surveillance Study for Intrauterine Devices.

PubMed

Heinemann, Klaas; Reed, Suzanne; Moehner, Sabine; Minh, Thai Do

2015-04-01

The objective was to measure the rate of unintended pregnancies in women using levonorgestrel-releasing intrauterine systems (LNG IUSs, releasing 20 mcg LNG daily) and copper intrauterine devices (IUDs) in a typical population of IUD users and to describe associated complications. A multinational, prospective, non-interventional cohort study of new users of LNG IUS and copper IUDs was performed. Following a baseline survey, study participants and their physicians completed one follow-up questionnaire after 12 months. A multifaceted four-level follow-up procedure minimized loss to follow-up. Patient-reported outcomes were validated by the treating physicians. A total of 61,448 women with a newly inserted IUD were enrolled in six European countries between 2006 and 2012. The copper IUD cohort contained more than 30 different types. Validated 1-year follow-up information for 58,324 users between 18 and 50 years of age (70% using LNG IUS, 30% using copper IUDs) was collected. A total of 118 contraceptive failures occurred (26 LNG, 92 copper). Both types of IUD were highly effective, with overall Pearl indices of 0.06 [95% confidence interval (CI): 0.04-0.09] and 0.52 (95% CI: 0.42-0.64) for LNG IUS and copper IUDs, respectively. The adjusted hazard ratio for LNG IUS vs. copper IUDs was 0.16 (95% CI: 0.10-0.25). Tenty-one pregnancies (7 LNG IUS, 14 copper IUD) were ectopic, yielding an adjusted hazard ratio for ectopic pregnancy of 0.26 (95% CI: 0.10-0.66). The contraceptive failure rate was low with both IUDs. However, the LNG IUS was associated with a significantly lower risk of pregnancy, including ectopic pregnancy, than the copper IUDs. To our knowledge, this is the first large-scale, multinational, prospective epidemiological study to measure and compare the contraceptive effectiveness of LNG IUSs and copper IUDs during routine clinical practice. Clinicians and patients should be aware of differences in rates of unintended pregnancies and associated complications

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

PubMed

Fung, Camille M; White, Jessica R; Brown, Ashley S; Gong, Huiyu; Weitkamp, Jörn-Hendrik; Frey, Mark R; McElroy, Steven J

2016-01-01

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

Estimating the relative contributions of maternal genetic, paternal genetic and intrauterine factors to offspring birth weight and head circumference

PubMed Central

Rice, Frances; Thapar, Anita

2010-01-01

Background Genetic factors and the prenatal environment contribute to birth weight. However, very few types of study design can disentangle their relative contribution. Aims To examine maternal genetic and intrauterine contributions to offspring birth weight and head circumference. To compare the contribution of maternal and paternal genetic effects. Study design Mothers and fathers were either genetically related or unrelated to their offspring who had been conceived by in vitro fertilization. Subjects 423 singleton full term offspring, of whom 262 were conceived via homologous IVF (both parents related), 66 via sperm donation (mother only related) and 95 via egg donation (father only related). Measures Maternal weight at antenatal booking, current weight and maternal height. Paternal current weight and height were all predictors. Infant birth weight and head circumference were outcomes. Results Genetic relatedness was the main contributing factor between measures of parental weight and offspring birth weight as correlations were only significant when the parent was related to the child. However, there was a contribution of the intrauterine environment to the association between maternal height and both infant birth weight and infant head circumference as these were significant even when mothers were unrelated to their child. Conclusions Both maternal and paternal genes made contributions to infant birth weight. Maternal height appeared to index a contribution of the intrauterine environment to infant growth and gestational age. Results suggested a possible biological interaction between the intrauterine environment and maternal inherited characteristics which suppresses the influence of paternal genes. PMID:20646882

Estimating the relative contributions of maternal genetic, paternal genetic and intrauterine factors to offspring birth weight and head circumference.

PubMed

Rice, Frances; Thapar, Anita

2010-07-01

Genetic factors and the prenatal environment contribute to birth weight. However, very few types of study design can disentangle their relative contribution. To examine maternal genetic and intrauterine contributions to offspring birth weight and head circumference. To compare the contribution of maternal and paternal genetic effects. Mothers and fathers were either genetically related or unrelated to their offspring who had been conceived by in vitro fertilization. 423 singleton full term offspring, of whom 262 were conceived via homologous IVF (both parents related), 66 via sperm donation (mother only related) and 95 via egg donation (father only related). Maternal weight at antenatal booking, current weight and maternal height. Paternal current weight and height were all predictors. Infant birth weight and head circumference were outcomes. Genetic relatedness was the main contributing factor between measures of parental weight and offspring birth weight as correlations were only significant when the parent was related to the child. However, there was a contribution of the intrauterine environment to the association between maternal height and both infant birth weight and infant head circumference as these were significant even when mothers were unrelated to their child. Both maternal and paternal genes made contributions to infant birth weight. Maternal height appeared to index a contribution of the intrauterine environment to infant growth and gestational age. Results suggested a possible biological interaction between the intrauterine environment and maternal inherited characteristics which suppresses the influence of paternal genes. 2010 Elsevier Ltd. All rights reserved.

Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

PubMed

Chen, L; Yue, J; Han, X; Li, J; Hu, Y

2016-02-01

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

Effectiveness of intrauterine treatment with cephapirin in dairy cows with purulent vaginal discharge.

PubMed

Tison, N; Bouchard, E; DesCôteaux, L; Lefebvre, R C

2017-02-01

The objective of this study was to assess the efficacy of cephapirin intrauterine treatment preceding a timed artificial insemination protocol in lactating dairy cows with purulent vaginal discharges (PVDs). Holstein dairy cows (n = 1247) from 18 herds were enrolled in a controlled randomized clinical trial. At 34 days in milk (DIM; ±7 days), cows had a genital examination (transrectal palpation, vaginoscopy, and uterine bacteriology). They were randomly assigned to either the control group (CONT, no treatment) or the treatment group (CEPH) consisting of 1 intrauterine infusion of 500-mg cephapirin benzathine (RCL) (Metricure, Merck Animal Health, Montreal, Canada) regardless of the uterine health status. All cows were systematically enrolled in a presynch-ovsynch protocol for the first insemination. A second genital examination was made 2 weeks later. Cows that received any systemic or local antibiotics 10 days prior sampling to the end of the synchronization protocol were excluded from the study. Reproductive data of cows were collected for at least 300 DIM, entered in a databank, and validated (health record management software, DSAHR). Pregnancy diagnosis was done by transrectal palpation at the routinely scheduled veterinarian visits. On the basis of the highest sum of sensibility and specificity for pregnancy status at 120 DIM, the optimal cutoff for vaginal discharge score was determined as the presence of cloudy discharge with or without purulent material (PVD+, score 2). With a prevalence of 21.6% at 34 DIM, PVD+ was detrimental to the first-service conception rate (FSCR; PVD+: 26 ± 5%; PVD-: 40 ± 3%; P = 0.02). The negative effect of PVD+ was indicated by a hazard ratio of 0.72 (chi-square = 8.58; P < 0.01; 95% confidence interval = 0.56-0.91). Treatment with cephapirin was associated with a significant improvement of the FSCR in PVD+ cows (PVD+ CEPH: 36 ± 5%, PVD+ CONT: 23 ± 5%; P < 0.05), although it did not produce a

Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.

PubMed

Bagley, Heidi N; Wang, Yan; Campbell, Michael S; Yu, Xing; Lane, Robert H; Joss-Moore, Lisa A

2013-01-01

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

Aging and insulin signaling differentially control normal and tumorous germline stem cells.

PubMed

Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

2015-02-01

Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Analysis of a renormalization group method and normal form theory for perturbed ordinary differential equations

NASA Astrophysics Data System (ADS)

DeVille, R. E. Lee; Harkin, Anthony; Holzer, Matt; Josić, Krešimir; Kaper, Tasso J.

2008-06-01

For singular perturbation problems, the renormalization group (RG) method of Chen, Goldenfeld, and Oono [Phys. Rev. E. 49 (1994) 4502-4511] has been shown to be an effective general approach for deriving reduced or amplitude equations that govern the long time dynamics of the system. It has been applied to a variety of problems traditionally analyzed using disparate methods, including the method of multiple scales, boundary layer theory, the WKBJ method, the Poincaré-Lindstedt method, the method of averaging, and others. In this article, we show how the RG method may be used to generate normal forms for large classes of ordinary differential equations. First, we apply the RG method to systems with autonomous perturbations, and we show that the reduced or amplitude equations generated by the RG method are equivalent to the classical Poincaré-Birkhoff normal forms for these systems up to and including terms of O(ɛ2), where ɛ is the perturbation parameter. This analysis establishes our approach and generalizes to higher order. Second, we apply the RG method to systems with nonautonomous perturbations, and we show that the reduced or amplitude equations so generated constitute time-asymptotic normal forms, which are based on KBM averages. Moreover, for both classes of problems, we show that the main coordinate changes are equivalent, up to translations between the spaces in which they are defined. In this manner, our results show that the RG method offers a new approach for deriving normal forms for nonautonomous systems, and it offers advantages since one can typically more readily identify resonant terms from naive perturbation expansions than from the nonautonomous vector fields themselves. Finally, we establish how well the solution to the RG equations approximates the solution of the original equations on time scales of O(1/ɛ).

Management of twin anemia-polycythemia sequence using intrauterine blood transfusion for the donor and partial exchange transfusion for the recipient.

PubMed

Genova, L; Slaghekke, F; Klumper, F J; Middeldorp, J M; Steggerda, S J; Oepkes, D; Lopriore, E

2013-01-01

Twin anemia-polycythemia sequence (TAPS) is a rare condition which may occur either spontaneously in uncomplicated monochorionic twin pregnancies or may develop after laser treatment in twin-twin transfusion syndrome. TAPS is characterized by a large intertwin discordance in hemoglobin levels without discordance in amniotic fluid levels, and may lead to severe complications including fetal hydrops, hematological morbidity and perinatal mortality. Several treatments have been proposed including intrauterine transfusion, laser surgery, elective delivery and expectant management. The optimal treatment remains unclear. In this case series we report 3 TAPS cases managed recently at our center with a combination of intrauterine blood transfusion for the anemic twin and intrauterine partial exchange transfusion for the polycythemic twin. In 1 case, the donor was found to have severe cerebral injury on neuroimaging examination. We propose etiologic mechanisms for cerebral injury in TAPS, discuss the rationale behind this treatment alternative, and evaluate the pros and cons of the various management options. Copyright © 2013 S. Karger AG, Basel.

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Hegui; He, Zheng; Zhu, Chunyan

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observedmore » in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.« less

Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

PubMed Central

Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

2008-01-01

Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane

2013-02-15

As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cellsmore » versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.« less

Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

PubMed

Hennig, Maria; Fiedler, Saskia; Jux, Christian; Thierfelder, Ludwig; Drenckhahn, Jörg-Detlef

2017-08-04

Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis†.

PubMed

Khan, Khaleque Newaz; Fujishita, Akira; Kitajima, Michio; Hiraki, Koichi; Nakashima, Masahiro; Masuzaki, Hideaki

2014-11-01

Is there any risk of intra-uterine bacterial colonization and concurrent occurrence of endometritis in women with endometriosis? An increase in intra-uterine microbial colonization and concurrent endometritis occurred in women with endometriosis that was further increased after GnRH agonist (GnRHa) treatment. Higher bacterial contamination of menstrual blood and increased endotoxin level in menstrual and peritoneal fluids have been found in women with endometriosis than in control women. However, information on intra-uterine microbial colonization across the phases of the menstrual cycle and possible occurrence of endometritis in women with endometriosis is still lacking. This is a case-controlled study with prospective collection of vaginal smears/endometrial samples from women with and without endometriosis and retrospective evaluation. Vaginal smears and endometrial smears were collected from 73 women with endometriosis and 55 control women. Twenty of the women with endometriosis and 19 controls had received GnRHa therapy for a period of 4-6 months. Vaginal pH was measured by intra-vaginal insertion of a pH paper strip. The bacterial vaginosis (BV) score was analyzed by Gram-staining of vaginal smears and based on a modified Nugent-BV scoring system. A panel of bacteria was analyzed by culture of endometrial samples from women treated with GnRHa or not treated. Immunohistochemcial analysis was performed using antibody against Syndecan-1 (CD138) and myeloperoxidase in endometrial biopsy specimens from women with and without endometriosis. A significant shifting of intra-vaginal pH to ≥4.5 was observed in women with endometriosis compared with control women (79.3 versus 58.4%, P < 0.03). Compared with untreated women, use of GnRHa therapy also shifted vaginal pH to ≥4.5 in both control women (P = 0.004) and in women with endometriosis (P = 0.03). A higher risk of increasing intermediate flora (total score, 4-6) (P = 0.05) was observed in women with

A simple implementation of a normal mixture approach to differential gene expression in multiclass microarrays.

PubMed

McLachlan, G J; Bean, R W; Jones, L Ben-Tovim

2006-07-01

An important problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. We provide a straightforward and easily implemented method for estimating the posterior probability that an individual gene is null. The problem can be expressed in a two-component mixture framework, using an empirical Bayes approach. Current methods of implementing this approach either have some limitations due to the minimal assumptions made or with more specific assumptions are computationally intensive. By converting to a z-score the value of the test statistic used to test the significance of each gene, we propose a simple two-component normal mixture that models adequately the distribution of this score. The usefulness of our approach is demonstrated on three real datasets.

Application of spectroscopy (1HMRS) to assess liver metabolite concentrations in rats with intrauterine growth restriction.

PubMed

Wang, Tao; Chen, Pingyang; Bian, Dujun; Chen, Juncao

2017-04-01

Proton magnetic resonance spectroscopy ( 1 H-MRS) measurement of liver metabolism in intrauterine growth restriction rats has seldom been reported. This study investigated the application of 1 H-MRS in assessing liver metabolism in newborn pups that experienced intrauterine growth restriction. Intra-uterine growth restriction was established by feeding rats low-protein diets during pregnancy. Newborn pups received conventional magnetic resonance imaging and 1 H-MRS using a 3.0T whole body MR scanner at 3, 8 and 12 weeks post birth. The success rate of 1 H-MRS was 83.33%. Significantly lower body weight, BMI and body length at 3 weeks as well as significantly lower body weight, BMI and waist circumference at 8 and 12 weeks were observed in newborn pups of IUGR rats compared with pups of control rats. Significant differences in ACho/H 2 O, ACr/H 2 O, AGlx/H 2 O and ALipid/H 2 O at 3 and 8 weeks as well as significant differences in ACr/H 2 O, ALipid/H 2 O and AGlx/H 2 O at 12 weeks were observed between pups of control rats and pups of IUGR rats. 1 H-MRS allows noninvasive assessment of liver metabolism in the rat and demonstrated the poor liver development of rats that experienced IUGR.

Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

PubMed

Setia, Sajita; Sridhar, M G; Koner, B C; Bobby, Zachariah; Bhat, Vishnu; Chaturvedula, Lata

2007-02-01

Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.

Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

PubMed Central

Bolton, Michael; Horvath, Dennis J.; Li, Birong; Cortado, Hanna; Newsom, David; White, Peter; Partida-Sanchez, Santiago; Justice, Sheryl S.

2012-01-01

Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organs PMID:22470490

Legionnaire's disease complicating pregnancy: a case report with intrauterine fetal demise.

PubMed

Vimercati, A; Greco, P; Bettocchi, S; Resta, L; Selvaggi, L

2000-01-01

Legionnaire's disease complicating pregnancy is an unusual event that can seriously compromise both the mother and the fetus. We describe one case of such association, with an unfavourable intrauterine fetal outcome, secondary to acute placental insufficiency, related to infection. It is important in these high risk pregnancies complicated by acute pneumonia to take into consideration the diagnosis, as early as possible, and the appropriate treatment or the careful monitoring of fetal wellbeing.

Hysteroscopic morcellator for removal of intrauterine polyps and myomas: a randomized controlled pilot study among residents in training.

PubMed

van Dongen, Heleen; Emanuel, Mark Hans; Wolterbeek, Ron; Trimbos, J Baptist; Jansen, Frank Willem

2008-01-01

The purpose of this randomized controlled study was to compare conventional resectoscopy and hysteroscopic morcellation among residents in training (Canadian Task Force classification I). Sixty women with an intrauterine polyp or myoma were randomized to either hysteroscopic removal by conventional resectoscopy or hysteroscopic morcellation performed by 6 residents in training for obstetrics and gynecology (10 procedures per resident). The mean operating time for resectosocpy and morcellation was 17.0 (95% confidence interval [95% CI] 14.1-17.9, standard deviation [SD] 8.4) and 10.6 (95% CI 7.3-14.0, SD 9.5) min, respectively (p = .008). Multiple linear regression analysis showed that operating time increased significantly, for both resectoscopy and morcellator, when volume of intrauterine disorder increased. The use of the hysteroscopic morcellator reduced operating time more than 8 min in comparison to conventional resectoscopy (p < .001) when correction for volume was applied. Subjective surgeon and trainer scores for convenience of technique on a visual analog scale were in favor of the morcellator. No learning curve was observed. In conclusion, the hysteroscopic morcellator for removal of intrauterine polyps and myomas offers a good alternative to conventional resectoscopy for residents in training.

Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques

PubMed Central

Brenner, Robert M.; Slayden, Ov D.; Nath, Anita; Tsong, YY; Sitruk-Ware, Regine

2010-01-01

Background Ulipristal (CDB-2914; UPA) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. Study Design Short lengths of Silastic tubing either empty (n=3), or containing UPA (n=5), were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. Results During treatment, animals with an empty IUS menstruated for a mean total of 11.66 ± 0.88 days while UPA-IUS treated animals bled for only 1 ± 0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. Conclusions In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal. PMID:20227552

Congenital infantile myofibroma causing intrauterine death in a twin

PubMed Central

Aye, Christina Yi Ling; Gould, Steve; Akinsola, S Adeyemi

2011-01-01

While infantile myofibromatosis is the most common mesenchymal tumour of infancy, only around 300 cases have been reported. The authors report a 33-year-old para 1 with an uncomplicated, dichorionic diamniotic twin pregnancy who was diagnosed with an intrauterine death of one twin at 36+5 weeks gestation. At caesarean section, a macerated male stillborn weighing 2.72 kg was delivered. Postmortem examination revealed a pedunculated lesion attached to the left shoulder and underlying muscle consistent with a congenital myofibroma. The cause of death was postulated to be haemorrhage from the tumour surface causing fetal anaemia. PMID:22674951

Growth patterns in children with intrauterine growth retardation and their correlation to neurocognitive development.

PubMed

Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Leitner, Yael; Geva, Ronny; Eshel, Rina; Harel, Shaul

2009-07-01

The relationship between somatic growth and neurocognitive outcome was studied in a cohort of 136 children with intrauterine growth retardation. The children were followed up from birth to 9 to 10 years of age by annual measurements of growth parameters, neurodevelopmental evaluations, and IQ. The rate of catch-up for height between 1 and 2 years of age was significantly higher than the catch-up for weight (P < .001). The cognitive outcome at 9 to 10 years correlated with head circumference at all ages. The neurodevelopmental outcome at 9 to 10 years correlated with weight at all ages. Correlation with head circumference was more significant with IQ, while with weight it was stronger with the neurodevelopmental score. Height at 1 year was a significant predictor for IQ and neurodevelopmental outcome at 9 to 10 years. These findings are of distinct importance for prediction of subsequent neurodevelopmental outcome in children with intrauterine growth retardation.

Management of initial bleeding or spotting after levonorgestrel-releasing intrauterine system placement: a randomized controlled trial.

PubMed

Sørdal, Terje; Inki, Pirjo; Draeby, John; O'Flynn, Mary; Schmelter, Thomas

2013-05-01

To assess the efficacy of tranexamic acid or mefenamic acid in the management of the initial "nuisance" bleeding or spotting in the period immediately after placement of the levonorgestrel-releasing intrauterine system. Women were randomized after levonorgestrel-releasing intrauterine system placement to oral tranexamic acid (500 mg), mefenamic acid (500 mg), or placebo three times daily during bleeding or spotting episodes over a 90-day treatment period. Treatment was initiated from onset of a bleeding or spotting episode and continued until the first day after bleeding or spotting stopped and restarted with a new bleeding or spotting episode. The primary efficacy variable was reduction in the number of bleeding or spotting days. Tranexamic acid and mefenamic acid were compared with placebo using a one-sided Wilcoxon rank-sum test. Bonferroni-Holm adjustment was used to account for multiple testing. A total of 204 women were screened; 187 were randomized to tranexamic acid (n=63), mefenamic acid (n=63), or placebo (n=61). The median number of bleeding or spotting days experienced during treatment was 25, 29, and 33 days in the three groups, respectively. The median number of bleeding or spotting days was reduced by 6 days (95% confidence interval [CI] -14.0 to 1.0, P=.049) with tranexamic acid and by 3 days (95% CI -11.0 to 5.0, P=.229) with mefenamic acid compared with placebo. The relative risk of bleeding or spotting compared with placebo with tranexamic acid and mefenamic acid was 0.82 (95% CI 0.65-1.03) and 0.89 (95% CI 0.71-1.11), respectively. Most women (85% or more) were satisfied with the levonorgestrel-releasing intrauterine system across the groups. Tranexamic acid and mefenamic acid during the first 90 days after levonorgestrel-releasing intrauterine system placement do not alleviate "nuisance" bleeding or spotting. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01295294. I.

[Associated factors in newborns with intrauterine growth retardation].

PubMed

Thompson-Chagoyán, Oscar C; Vega-Franco, Leopoldo

2008-01-01

To identify the risk factors implicated in the intrauterine growth retardation (IUGR) of neonates born in a social security institution. Case controls design study in 376 neonates: 188 with IUGR (weight < 10 percentile) and 188 without IUGR. When they born, information about 30 variables of risk for IUGR were obtained from mothers. Risk analysis and logistical regression (stepwise) were used. Odds ratios were significant for 12 of the variables. The model obtains by stepwise regression included: weight gain at pregnancy, prenatal care attendance, toxemia, chocolate ingestion, father's weight, and the environmental house. Must of the variables included in the model are related to socioeconomic disadvantages related to the risk of RCIU in the population.

Challenges in nourishing the intrauterine growth-restricted foetus - Lessons learned from studies in the intrauterine growth-restricted foetal sheep.

PubMed

Hay, William W; Brown, Laura D; Rozance, Paul J; Wesolowski, Stephanie R; Limesand, Sean W

2016-08-01

Previous attempts to improve growth and development of the intrauterine growth-restricted (IUGR) foetus during pregnancy have not worked or caused harm. Our research identifies tissue-specific mechanisms underlying foetal growth restriction and then tests strategies to improve growth and ameliorate many of the metabolic problems before the infant is born. The goal of our studies is to reduce the impact of foetal growth restriction at critical stages of development on the lifelong complications of IUGR offspring. Defining specific mechanisms that cause growth restriction in the foetus might identify specific nutrients and hormones that could be given to the mother to improve foetal growth and reduce metabolic complications, using strategies first tested in our IUGR animal model. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

Opitz, Robert; Maquet, Emilie; Zoenen, Maxime; Dadhich, Rajesh

2011-01-01

TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. PMID:21737742

Postplacental or Delayed Insertion of the Levonorgestrel Intrauterine Device After Vaginal Delivery

PubMed Central

Chen, Beatrice A.; Reeves, Matthew F.; Hayes, Jennifer L.; Hohmann, Heather L.; Perriera, Lisa K.; Creinin, Mitchell D.

2011-01-01

OBJECTIVE To estimate whether 6-month use of the levonorgestrel-releasing intrauterine device (IUD) would be higher when insertion occurred within 10 minutes of placental delivery compared with 6–8 weeks postpartum. METHODS We enrolled pregnant women planning vaginal deliveries and desiring a postpartum levonorgestrel-releasing IUD. Patients were randomly assigned when admitted in labor to postplacental or delayed IUD insertion. The women followed up in person at 6–8 weeks and 6 months and were contacted by telephone at 3 months. Women were ineligible for a study IUD postenrollment for intrapartum events including infection, hemorrhage, and cesarean delivery; these women were contacted by phone at 3 and 6 months. Expelled IUDs were replaced per patient preference. RESULTS Successful IUD placement occurred in 50 of 51 participants (98.0%) and 46 of 51 participants (90.2%) in the postplacental and delayed groups, respectively (P=.2). Expulsion within 6 months occurred in 12 of 50 (24.0%; 95% confidence interval [CI], 13.1–38.2) and two of 46 (4.4%; 95% CI 0.5–14.8) participants, respectively (P=.008). Intrauterine device use at 6 months was 43 of 51 (84.3%; 95% CI 71.4–93.0) and 39 of 51 (76.5%; 95% CI 62.5–87.2), respectively (P=.32). For ineligible patients, only 11 of 41 (26.8%) women were using IUDs at 6 months and two (4.9%) had become pregnant. CONCLUSION Intrauterine device use 6 months after delivery is similar in women who have postpartum or scheduled delayed IUD placement through a study after replacement of expelled IUDs. Expulsions are significantly higher with postplacental compared with delayed IUD placement. Women asked to follow up with their own health care providers for delayed insertion are significantly less likely to receive an IUD. CLINICALTRIALREGISTRATION ClinicalTrials.gov, www.clinicaltrials.gov, NCT00476021. LEVEL OF EVIDENCE I PMID:20966692

ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.

PubMed

Nair, Nishanth Ulhas; Sahu, Avinash Das; Bucher, Philipp; Moret, Bernard M E

2012-01-01

The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html.

Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

NASA Technical Reports Server (NTRS)

Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

2002-01-01

During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

Cerebral metabolic intermediate response following severe canine intrauterine growth retardation.

PubMed

Kliegman, R M

1986-07-01

The effect of intrauterine growth retardation and neonatal hypoglycemia on cerebral metabolic intermediates were determined in newborn dogs subjected to 5 days of maternal canine starvation (MCS) before birth. Birth weight was reduced 23% (232 +/- 6 versus 300 +/- 10 g). Circulating blood glucose was reduced after 3 h of neonatal fasting in MCS pups (2.7 +/- 0.4 +/- versus 5.7 +/- 1.1 mM). Cerebral cortical levels of glucose were also reduced at this time. Cerebral glucose-6-phosphate was not altered; nonetheless fructose-6-phosphate was lower in MCS pups at 6 and 9 h, while fructose 1,6-diphosphate appeared elevated at 3 h. These data suggest that cerebral glycolytic activity may be increased by increased activity of phosphofructokinase. Cerebral glutamine appeared reduced in fasting MCS pups at 3, 6, and 8 h of age. A considerable disturbance of the adenine nucleotide pool was noted between 3-9 h in MCS pups; while the cerebral energy reserve was diminished in MCS pups between 3-24 h. The data of reduced cerebral energy status and reserve suggest that cerebral energy production was diminished. Although glucose levels were low at 3 h, subsequent recovery was not immediate as adenine-nucleotides remained low beyond the period of hypoglycemia. The combined effects of intrauterine growth retardation and transient neonatal hypoglycemia appear to result in reduced cerebral oxidative metabolism; this occurs despite an apparent enhanced utilization of alternate fuels.

Decreased endometrial HOXA10 expression associated with use of the copper intrauterine-device

PubMed Central

Tetrault, Amy M; Richman, Susan M; Fei, Xiaolan; Taylor, Hugh S

2009-01-01

Objective To characterize human endometrial HOXA10 expression in patients using copper intrauterine devices (IUD). Design Case-control study. Setting Academic medical center Patient(s) Women using copper IUD Interventions(s) Immunohistochemical analysis of endometrial HOXA10 expression in biopsies obtained from 24 women using copper Paraguard T380A as well as in biopsies obtained from 10 normal cycling women who were not using IUD or hormonal contraceptives. Main Outcome Measure(s) Endometrial HOXA10 expression. Result(s) Endometrial HOXA10 expression was markedly decreased in biopsies obtained from women using IUD contraceptive when compared to controls. The mean H score for endometrial stromal cell HOXA10 expression in biopsies obtained from women using Paraguard IUD was 0.21 compared to 2.2 in the control endometrial biopsies (P<0.001). Endometrial glandular expression of HOXA10 was absent in all IUD users. Conclusion(s) Decreased endometrial HOXA10 expression was apparent in women who use a copper IUD. Expression of HOXA10 is essential for endometrial receptivity. A novel mechanism of copper IUD action involves suppression of genes required for endometrial receptivity. The dramatic decrease of endometrial HOXA10 in response to IUD use may contribute to contraceptive efficacy. PMID:18930214

Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

PubMed

Wang, Yan; Fu, Wei; Liu, Jing

2016-01-01

Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

GC-Content Normalization for RNA-Seq Data

PubMed Central

2011-01-01

Background Transcriptome sequencing (RNA-Seq) has become the assay of choice for high-throughput studies of gene expression. However, as is the case with microarrays, major technology-related artifacts and biases affect the resulting expression measures. Normalization is therefore essential to ensure accurate inference of expression levels and subsequent analyses thereof. Results We focus on biases related to GC-content and demonstrate the existence of strong sample-specific GC-content effects on RNA-Seq read counts, which can substantially bias differential expression analysis. We propose three simple within-lane gene-level GC-content normalization approaches and assess their performance on two different RNA-Seq datasets, involving different species and experimental designs. Our methods are compared to state-of-the-art normalization procedures in terms of bias and mean squared error for expression fold-change estimation and in terms of Type I error and p-value distributions for tests of differential expression. The exploratory data analysis and normalization methods proposed in this article are implemented in the open-source Bioconductor R package EDASeq. Conclusions Our within-lane normalization procedures, followed by between-lane normalization, reduce GC-content bias and lead to more accurate estimates of expression fold-changes and tests of differential expression. Such results are crucial for the biological interpretation of RNA-Seq experiments, where downstream analyses can be sensitive to the supplied lists of genes. PMID:22177264

Reversible effects of oxygen partial pressure on genes associated with placental angiogenesis and differentiation in primary-term cytotrophoblast cell culture.

PubMed

Debiève, F; Depoix, C; Gruson, D; Hubinont, C

2013-09-01

Timely regulated changes in oxygen partial pressure are important for placental formation. Disturbances could be responsible for pregnancy-related diseases like preeclampsia and intrauterine growth restriction. We aimed to (i) determine the effect of oxygen partial pressure on cytotrophoblast differentiation; (ii) measure mRNA expression and protein secretion from genes associated with placental angiogenesis; and (iii) determine the reversibility of these effects at different oxygen partial pressures. Term cytotrophoblasts were incubated at 21% and 2.5% O2 for 96 hr, or were switched between the two oxygen concentrations after 48 hr. Real-time PCR and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate cell fusion and differentiation, measuring transcript levels for those genes involved in cell fusion and placental angiogenesis, including VEGF, PlGF, VEGFR1, sVEGFR1, sENG, INHA, and GCM1. Cytotrophoblasts underwent fusion and differentiation in 2.5% O2 . PlGF expression was inhibited while sVEGFR1 expression increased. VEGF and sENG mRNA expressions increased in 2.5% compared to 21% O2 , but no protein was detected in the cell supernatants. Finally, GCM1 mRNA expression increased during trophoblast differentiation at 21% O2 , but was inhibited at 2.5% O2 . These mRNA expression effects were reversed by returning the cells to 21% O2 . Thus, low-oxygen partial pressure does not inhibit term-cytotrophoblast cell fusion and differentiation in vitro. Lowering the oxygen partial pressure from 21% to 2.5% caused normal-term trophoblasts to reversibly modify their expression of genes associated with placental angiogenesis. This suggests that modifications observed in pregnancy diseases such as preeclampsia or growth retardation are probably due to an extrinsic effect on trophoblasts. Copyright © 2013 Wiley Periodicals, Inc.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

PubMed

Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

2016-07-01

Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial

PubMed Central

Strug, Michael R.; Su, Renwei; Young, James E.; Dodds, William G.; Shavell, Valerie I.; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A.; Leach, Richard E.; Fazleabas, Asgerally T.

2016-01-01

STUDY QUESTION Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? SUMMARY ANSWER Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. WHAT IS KNOWN ALREADY The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. STUDY DESIGN, SIZE, DURATION Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. PARTICIPANTS/MATERIALS, SETTING, METHODS Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT–PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. MAIN RESULTS AND THE ROLE OF CHANCE Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were

Small Size at Birth or Abnormal Intrauterine Growth Trajectory: Which Matters More for Child Growth?

PubMed Central

Hutcheon, Jennifer A.; Jacobsen, Geir W.; Kramer, Michael S.; Martinussen, Marit; Platt, Robert W.

2016-01-01

Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986–1988). Size at birth was classified using birth weight-for-gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks’ gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (β = 0.24 (95% confidence interval (CI): 0.18, 0.31), β = 0.16 (95% CI: 0.09, 0.23), β = 0.08 (95% CI: 0.01, 0.16), and β = 0.37 (95% CI: 0.22, 0.52), respectively). However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R2 increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional insight into child growth beyond that obtained from absolute size at birth. PMID:27257112

Are There Effects of Intrauterine Cocaine Exposure on Delinquency during Early Adolescence? A Preliminary Report

PubMed Central

Gerteis, Jessie; Chartrand, Molinda; Martin, Brett; Cabral, Howard J.; Rose-Jacobs, Ruth; Crooks, Denise; Frank, Deborah A.

2011-01-01

Objective To ascertain whether level of intrauterine cocaine exposure (IUCE) is associated with early adolescent delinquent behavior, after accounting for prenatal exposures to other psychoactive substances and relevant psychosocial factors. Methods Ninety-three early adolescents (12.5–14.5 years old) participating since birth in a longitudinal study of IUCE reported delinquent acts via an audio computer assisted self interview (ACASI). Level of IUCE and exposure to cigarettes, alcohol, and marijuana were determined by maternal report, maternal and infant urine assays, and infant meconium assays at birth. Participants reported their exposure to violence on the Violence Exposure Scale for Children – Revised (VEX-R) at ages 8.5, 9.5, 11 years and during early adolescence, and the strictness of supervision by their caregivers during early adolescence. Results Of the 93 participants, 24 (26%) reported ≥3 delinquent behaviors during early adolescence. In the final multivariate model (including level of IUCE and cigarette exposure, childhood exposure to violence, and caregiver strictness/supervision) ≥ 3 delinquent behaviors were not significantly associated with level of IUCE but were significantly associated with intrauterine exposure to half a pack or more of cigarettes per day and higher levels of childhood exposure to violence, effects substantially unchanged after control for early adolescent violence exposure. Conclusions In this cohort, prospectively ascertained prenatal exposure to cigarettes and childhood exposure to violence are associated with self-reported delinquent behaviors during early adolescence. Contrary to initial popular predictions, intrauterine cocaine is not a strong predictor of adolescent delinquent behaviors in this cohort. PMID:21558951

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial.

PubMed

Norman, Wendy V; Kaczorowski, Janusz; Soon, Judith A; Brant, Rollin; Bryan, Stirling; Trouton, Konia J; Dicus, Lyda

2011-06-14

We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight

A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction.

PubMed

Kwiatkowski, Sebastian; Dołęgowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Torbè, Andrzej; Bednarek-Jędrzejek, Magdalena

2016-01-01

Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and 'placental' intrauterine growth restriction patients, which could be used in developing

Application of a hyaluronic acid gel after intrauterine surgery may improve spontaneous fertility: a randomized controlled trial in New Zealand White rabbits.

PubMed

Huberlant, Stephanie; Fernandez, Herve; Vieille, Pierre; Khrouf, Mohamed; Ulrich, Daniela; deTayrac, Renaud; Letouzey, Vincent

2015-01-01

Intrauterine adhesions (IUAs) are the most common complication after hysteroscopy in patients of reproductive age. Intra-abdominal anti-adhesion gel reduces the incidence of adhesions, but effects on fertility after uterine surgery are not known. The objective of our work was to evaluate the effect of intrauterine anti-adhesion gel on spontaneous fertility after repeated intrauterine surgery with induced experimental synechiae in the rabbit model. Twenty New Zealand White rabbits underwent a double uterine curettage 10 days apart and were randomized into two groups. Each rabbit served as its own control: one uterine tube was the treatment group (A), the second uterine tube was the control group (B) to avoid bias through other causes of infertility. Group A received a post curettage intrauterine instillation of anti-adhesion gel whereas group B, the control group, underwent curettage without instillation of the gel. After a recovery period, the rabbits were mated. An abdominal ultrasound performed 21 days after mating allowed us to diagnose pregnancy and quantify the number of viable fetuses. There was a significant difference in total fetuses in favor of group A, with an average of 3.7 (range, 0-9) total fetuses per tube against 2.1 (0-7) in group B (p = .04). The number of viable fetuses shows a trend in favor of group A, with an average of 3.4 (0-7) viable fetuses per tube against 1.9 (0-6) viable fetuses per tube in group B (p = .05). The use of immediate postoperative anti-adhesion gel improved fertility in an animal model after intrauterine surgery likely to cause uterine synechiae. This experimental model will permit comparison of different anti-adhesion solutions, including assessment of their tolerance and potential mucosal toxicity on embryonic development.

Detection of colorectal masses in CT colonography: application of deep residual networks for differentiating masses from normal colon anatomy

NASA Astrophysics Data System (ADS)

Näppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki

2018-02-01

Even though the clinical consequences of a missed colorectal cancer far outweigh those of a missed polyp, there has been little work on computer-aided detection (CADe) for colorectal masses in CT colonography (CTC). One of the problems is that it is not clear how to manually design mathematical image-based features that could be used to differentiate effectively between masses and certain types of normal colon anatomy such as ileocecal valves (ICVs). Deep learning has demonstrated ability to automatically determine effective discriminating features in many image-based problems. Recently, residual networks (ResNets) were developed to address the practical problems of constructing deep network architectures for optimizing the performance of deep learning. In this pilot study, we compared the classification performance of a conventional 2D-convolutional ResNet (2D-ResNet) with that of a volumetric 3D-convolutional ResNet (3D-ResNet) in differentiating masses from normal colon anatomy in CTC. For the development and evaluation of the ResNets, 695 volumetric images of biopsy-proven colorectal masses, ICVs, haustral folds, and rectal tubes were sampled from 196 clinical CTC cases and divided randomly into independent training, validation, and test datasets. The training set was expanded by use of volumetric data augmentation. Our preliminary results on the 140 test samples indicate that it is feasible to train a deep volumetric 3D-ResNet for performing effective image-based discriminations in CTC. The 3D-ResNet slightly outperformed the 2D-ResNet in the discrimination of masses and normal colon anatomy, but the statistical difference between their very high classification accuracies was not significant. The highest classification accuracy was obtained by combining the mass-likelihood estimates of the 2D- and 3D-ResNets, which enabled correct classification of all of the masses.

Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial.

PubMed

Weiss, Nienke S; Nahuis, Marleen J; Bordewijk, Esmee; Oosterhuis, Jurjen E; Smeenk, Jesper Mj; Hoek, Annemieke; Broekmans, Frank Jm; Fleischer, Kathrin; de Bruin, Jan Peter; Kaaijk, Eugenie M; Laven, Joop Se; Hendriks, Dave J; Gerards, Marie H; van Rooij, Ilse Aj; Bourdrez, Petra; Gianotten, Judith; Koks, Carolien; Lambalk, Cornelis B; Hompes, Peter G; van der Veen, Fulco; Mol, Ben Willem J; van Wely, Madelon

2018-02-24

In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse. In this two-by-two factorial multicentre randomised clinical trial, we recruited women aged 18 years and older with normogonadotropic anovulation not pregnant after six ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days) from 48 Dutch hospitals. Women were randomly assigned using a central password-protected internet-based randomisation programme to receive six cycles with gonadotrophins plus intrauterine insemination, six cycles with gonadotrophins plus intercourse, six cycles with clomifene citrate plus intrauterine insemination, or six cycles with clomifene citrate plus intercourse. Clomifene citrate dosages varied from 50 to 150 mg daily orally and gonadotrophin starting dose was 50 or 75 IU daily subcutaneously. The primary outcome was conception leading to livebirth within 8 months after randomisation defined as any baby born alive after a gestational age beyond 24 weeks. Primary analysis was by intention to treat. We made two comparisons, one in which gonadotrophins were compared with clomifene citrate and one in which intrauterine insemination was compared with intercourse. This completed study is registered with the Netherlands Trial Register, number NTR1449. Between Dec 8, 2008, and Dec 16, 2015, we randomly assigned 666 women to gonadotrophins and intrauterine insemination (n=166), gonadotrophins and intercourse (n=165), clomifene citrate and intrauterine insemination (n=163), or clomifene citrate and intercourse (n=172). Women

[Exercise-induced oedema due to hormone-containing intrauterine device].

PubMed

Franssen, Laurens E; Bos, Willem-Jan W

2012-01-01

Oedema is a known adverse effect of the levonorgestrel-containing intrauterine device (Mirena IUD). However, exercise-induced oedema has not been described before. A 38-year-old woman presented with symptoms of diffuse, exercise-induced oedema and dyspnoea. Tests for heart failure and other causes of oedema showed no abnormalities. All symptoms resolved spontaneously after the patient initiated removal of the IUD. The pathophysiology of exercise-induced oedema is still poorly understood. When confronted with a patient with oedema (induced by exercise or other cause), the most common causes must first be excluded. If no explanation can be found, then the effects of medication must not be overlooked.

Group B streptococci in women fitted with intrauterine devices.

PubMed Central

Mitchell, R G; Guillebaud, J; Day, D G

1977-01-01

A survey was made of group B streptococcal carriage at various sites in 100 women attending a clinic for the insertion of an intrauterine contraceptive device (IUD). Twenty-three women carried streptococci at one or more sites at the preinsertion visit, the vaginal carriage rate being 16%. Six months after insertion changes in carrier status were noted and there was evidence of a change of strain in four patients. Twenty-nine women were carriers at one or more sites at some stage of the study. There was no evidence that symptoms attributable to infection in patients fitted with an IUD were caused by group B streptococci. PMID:338639

[Intrauterine device: about a rare complication and literature review].

PubMed

Kallat, Adil; Ibrahimi, Ahmed; Fahsi, Otheman; El Sayegh, Hachem; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

2017-01-01

The intrauterine device (IUD) is the most common contraceptive method used in the world. Transuterine migration is a rare complication, accounting for 1/350 - 1/10000 insertions in the literature. We report the case of a 40-year old patient, who had had an IUD insertion 12-year before, presenting with pelvic and right lower back pain associated with intermittent hematuria and burning during urination. Radiological assessment showed calcific deposits on intra bladder IUD. The patient underwent cystostomy, without any difficulty, allowing stone and IUD extraction. A urinary catheter was left in place for 5 days and then withdrawn. The postoperative course was uneventful.

Meconium proteins as a source of biomarkers for the assessment of the intrauterine environment of the fetus.

PubMed

Lisowska-Myjak, B; Skarżyńska, E; Bakun, M

2018-06-01

Intrauterine environmental factors can be associated with perinatal complications and long-term health outcomes although the underlying mechanisms remain poorly defined. Meconium formed exclusively in utero and passed naturally by a neonate may contain proteins which characterise the intrauterine environment. The aim of the study was proteomic analysis of the composition of meconium proteins and their classification by biological function. Proteomic techniques combining isoelectrofocussing fractionation and LC-MS/MS analysis were used to study the protein composition of a meconium sample obtained by pooling 50 serial meconium portions from 10 healthy full-term neonates. The proteins were classified by function based on the literature search for each protein in the PubMed database. A total of 946 proteins were identified in the meconium, including 430 proteins represented by two or more peptides. When the proteins were classified by their biological function the following were identified: immunoglobulin fragments and enzymatic, neutrophil-derived, structural and fetal intestine-specific proteins. Meconium is a rich source of proteins deposited in the fetal intestine during its development in utero. A better understanding of their specific biological functions in the intrauterine environment may help to identify these proteins which may serve as biomarkers associated with specific clinical conditions/diseases with the possible impact on the fetal development and further health consequences in infants, older children and adults.

[Customized and non-customized French intrauterine growth curves. II - Comparison with existing curves and benefits of customization].

PubMed

Ego, A; Prunet, C; Blondel, B; Kaminski, M; Goffinet, F; Zeitlin, J

2016-02-01

Our aim is to compare the new French EPOPé intrauterine growth curves, developed to address the guidelines 2013 of the French College of Obstetricians and Gynecologists, with reference curves currently used in France, and to evaluate the consequences of their adjustment for fetal sex and maternal characteristics. Eight intrauterine and birthweight curves, used in France were compared to the EPOPé curves using data from the French Perinatal Survey 2010. The influence of adjustment on the rate of SGA births and the characteristics of these births was analysed. Due to their birthweight values and distribution, the selected intrauterine curves are less suitable for births in France than the new curves. Birthweight curves led to low rates of SGA births from 4.3 to 8.5% compared to 10.0% with the EPOPé curves. The adjustment for maternal and fetal characteristics avoids the over-representation of girls among SGA births, and reclassifies 4% of births. Among births reclassified as SGA, the frequency of medical and obstetrical risk factors for growth restriction, smoking (≥10 cigarettes/day), and neonatal transfer is higher than among non-SGA births (P<0.01). The EPOPé curves are more suitable for French births than currently used curves, and their adjustment improves the identification of mothers and babies at risk of growth restriction and poor perinatal outcomes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Intrauterine growth and intelligence within sibling pairs: findings from the Mater-University study of pregnancy and its outcomes.

PubMed

Lawlor, Debbie A; Bor, William; O'Callaghan, Michael J; Williams, Gail M; Najman, Jake M

2005-04-01

To examine the association between intrauterine growth and intelligence. Population based birth cohort study of sibling pairs born within a maximum of three years of each other. Mater-University women and children's hospital, Brisbane, Australia. 235 (470 children) sibling pairs. Among one randomly selected sibling from each pair verbal comprehension at age 5, general intelligence at age 14, and reading ability at age 14 increased linearly with increasing gestational age and sex standardised birth weight z scores. With adjustment for maternal age, race, and smoking during pregnancy, birth order, family income, and parental education the associations with verbal comprehension at age 5 and general intelligence at age 14 remained, whereas the association with reading ability at age 14 was attenuated to the null. Within sibling pairs, differences in intrauterine growth were positively associated with differences in verbal comprehension at age 5 (test score difference per one unit difference in birth weight z score = 1.52 (0.11 to 3.26)) and general intelligence at age 14 (1.09 (0.01 to 2.18)), but not with reading ability at age 14. Socioeconomic position or other fixed maternal characteristics do not seem to explain the positive association between intrauterine growth and childhood intelligence.

Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

PubMed

Dikbas, Levent; Yapca, Omer Erkan; Dikbas, Neslihan; Gundogdu, Cemal

2017-05-01

Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

miRNA Temporal Analyzer (mirnaTA): a bioinformatics tool for identifying differentially expressed microRNAs in temporal studies using normal quantile transformation.

PubMed

Cer, Regina Z; Herrera-Galeano, J Enrique; Anderson, Joseph J; Bishop-Lilly, Kimberly A; Mokashi, Vishwesh P

2014-01-01

Understanding the biological roles of microRNAs (miRNAs) is a an active area of research that has produced a surge of publications in PubMed, particularly in cancer research. Along with this increasing interest, many open-source bioinformatics tools to identify existing and/or discover novel miRNAs in next-generation sequencing (NGS) reads become available. While miRNA identification and discovery tools are significantly improved, the development of miRNA differential expression analysis tools, especially in temporal studies, remains substantially challenging. Further, the installation of currently available software is non-trivial and steps of testing with example datasets, trying with one's own dataset, and interpreting the results require notable expertise and time. Subsequently, there is a strong need for a tool that allows scientists to normalize raw data, perform statistical analyses, and provide intuitive results without having to invest significant efforts. We have developed miRNA Temporal Analyzer (mirnaTA), a bioinformatics package to identify differentially expressed miRNAs in temporal studies. mirnaTA is written in Perl and R (Version 2.13.0 or later) and can be run across multiple platforms, such as Linux, Mac and Windows. In the current version, mirnaTA requires users to provide a simple, tab-delimited, matrix file containing miRNA name and count data from a minimum of two to a maximum of 20 time points and three replicates. To recalibrate data and remove technical variability, raw data is normalized using Normal Quantile Transformation (NQT), and linear regression model is used to locate any miRNAs which are differentially expressed in a linear pattern. Subsequently, remaining miRNAs which do not fit a linear model are further analyzed in two different non-linear methods 1) cumulative distribution function (CDF) or 2) analysis of variances (ANOVA). After both linear and non-linear analyses are completed, statistically significant miRNAs (P < 0

Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep.

PubMed

González-Candia, Alejandro; Veliz, Marcelino; Araya, Claudio; Quezada, Sebastian; Ebensperger, Germán; Serón-Ferré, María; Reyes, Roberto V; Llanos, Aníbal J; Herrera, Emilio A

2016-08-01

Intrauterine growth restriction is a condition in which the fetus has a birthweight and/or length <10th percentile for the gestational age. Intrauterine growth restriction can be associated with various causes, among which is low uteroplacental perfusion and chronic hypoxia during gestation. Often, intrauterine growth-restricted fetuses have increased oxidative stress; therefore, agents that decrease oxidative stress and increase utero, placental, and umbilical perfusion have been proposed as a beneficial therapeutic strategy. In this scenario, melatonin acts as an umbilical vasodilator and a potent antioxidant that has not been evaluated in pregnancies under chronic hypoxia that induce fetal growth restriction. However, this neurohormone has been proposed as a pharmacologic therapy for complicated pregnancies. The aim of this study was to determine the effects of prenatal administration of melatonin during the last trimester of pregnancy on the biometry of the growth-restricted lambs because of developmental hypoxia. Further, we aimed to determine melatonin and cortisol levels and oxidative stress markers in plasma of pregnant ewes during the treatment. High-altitude pregnant sheep received either vehicle (n = 5; 5 mL 1.4% ethanol) or melatonin (n = 7; 10 mg/kg(-1)day(-1) in 5 mL 1.4% ethanol) daily during the last one-third of gestation. Maternal plasma levels of melatonin, cortisol, antioxidant capacity, and oxidative stress were determined along treatment. At birth, neonates were examined, weighed, and measured (biparietal diameter, abdominal diameter, and crown-rump length). Antenatal treatment with melatonin markedly decreased neonatal biometry and weight at birth. Additionally, melatonin treatment increased the length of gestation by 7.5% and shifted the time of delivery. Furthermore, the prenatal treatment doubled plasma levels of melatonin and cortisol and significantly improved the antioxidant capacity of the pregnant ewes. Our findings indicate that

Comparative intrauterine development and placental function of ART concepti: implications for human reproductive medicine and animal breeding

PubMed Central

Bloise, Enrrico; Feuer, Sky K.; Rinaudo, Paolo F.

2014-01-01

BACKGROUND The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed. METHODS Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports. RESULTS ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures. CONCLUSIONS ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves

Elemental analysis of tissue pellets for the differentiation of epidermal lesion and normal skin by laser-induced breakdown spectroscopy

PubMed Central

Moon, Youngmin; Han, Jung Hyun; Shin, Sungho; Kim, Yong-Chul; Jeong, Sungho

2016-01-01

By laser induced breakdown spectroscopy (LIBS) analysis of epidermal lesion and dermis tissue pellets of hairless mouse, it is shown that Ca intensity in the epidermal lesion is higher than that in dermis, whereas Na and K intensities have an opposite tendency. It is demonstrated that epidermal lesion and normal dermis can be differentiated with high selectivity either by univariate or multivariate analysis of LIBS spectra with an intensity ratio difference by factor of 8 or classification accuracy over 0.995, respectively. PMID:27231610

Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

PubMed

Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

2015-01-01

Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

MRI Differences Associated with Intrauterine Growth Restriction in Preterm Infants.

PubMed

Bruno, Christie J; Bengani, Shreyans; Gomes, William A; Brewer, Mariana; Vega, Melissa; Xie, Xianhong; Kim, Mimi; Fuloria, Mamta

2017-01-01

Preterm infants are at risk for neurodevelopmental impairment. Intrauterine growth restriction (IUGR) further increases this risk. Brain imaging studies are often utilized at or near term-equivalent age to determine later prognosis. To evaluate the association between intrauterine growth and regional brain volume on MRI scans performed in preterm infants at or near term-equivalent age. This is a retrospective case-control study of 24 infants born at gestational age ≤30 weeks and cared for in a large, inner-city, academic neonatal intensive-care unit from 2012 to 2013. Each IUGR infant was matched with 1-2 appropriate for gestational age (AGA) infants who served as controls. Predischarge MRI scans routinely obtained at ≥36 weeks' adjusted age were analyzed for regional brain volumetric differences. We examined the association between IUGR and thalamic, basal ganglion, and cerebellar brain volumes in these preterm infants. Compared to AGA infants, IUGR infants had a smaller thalamus (7.88 vs. 5.87 mL, p = 0.001) and basal ganglion (8.87 vs. 6.92 mL, p = 0.002) volumes. There was no difference in cerebellar volumes between the two study groups. Linear regression analyses revealed similar trends in the associations between IUGR and brain volumes after adjusting for sex, gestational age at birth, and postconceptual age and weight at MRI. Thalamus and basal ganglion volumes are reduced in growth-restricted preterm infants. These differences may preferentially impact neurodevelopmental outcomes. Further research is needed to explore these relationships. © 2017 S. Karger AG, Basel.

Human Keratinocytes That Express hTERT and Also Bypass a p16INK4a-Enforced Mechanism That Limits Life Span Become Immortal yet Retain Normal Growth and Differentiation Characteristics

PubMed Central

Dickson, Mark A.; Hahn, William C.; Ino, Yasushi; Ronfard, Vincent; Wu, Jenny Y.; Weinberg, Robert A.; Louis, David N.; Li, Frederick P.; Rheinwald, James G.

2000-01-01

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in normal human fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly. Telomerase expression alone is insufficient to enable certain other cell types to evade senescence, however. Such cells, including keratinocytes and mammary epithelial cells, appear to require loss of the pRB/p16INK4a cell cycle control mechanism in addition to hTERT expression to achieve immortality. To investigate the relationships among telomerase activity, cell cycle control, senescence, and differentiation, we expressed hTERT in two epithelial cell types, keratinocytes and mesothelial cells, and determined the effect on proliferation potential and on the function of cell-type-specific growth control and differentiation systems. Ectopic hTERT expression immortalized normal mesothelial cells and a premalignant, p16INK4a-negative keratinocyte line. In contrast, when four keratinocyte strains cultured from normal tissue were transduced to express hTERT, they were incompletely rescued from senescence. After reaching the population doubling limit of their parent cell strains, hTERT+ keratinocytes entered a slow growth phase of indefinite length, from which rare, rapidly dividing immortal cells emerged. These immortal cell lines frequently had sustained deletions of the CDK2NA/INK4A locus or otherwise were deficient in p16INK4a expression. They nevertheless typically retained other keratinocyte growth controls and differentiated normally in culture and in xenografts. Thus, keratinocyte replicative potential is limited by a p16INK4a-dependent mechanism, the activation of which can occur independent of telomere length. Abrogation of this mechanism together with telomerase expression immortalizes keratinocytes

Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2012-06-01

The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2 ± 4.3 ng/ml in the IUGR group, 14.1 ± 3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1 ± 3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6 ± 3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and

Ultrasonographic visualization of bleeding sites can help control postpartum hemorrhage using intrauterine balloon tamponade.

PubMed

Kondoh, Eiji; Konishi, Mitsunaga; Kariya, Yoshitaka; Konishi, Ikuo

2015-01-01

Identification of precise bleeding sites is generally important to control hemorrhage. Nevertheless, the optimal technique to detect the bleeding sites has not yet been fully defined for patients with life-threatening post partum hemorrhage. We describe that ultrasonographic visualization of bleeding sites can help control post partum hemorrhage using intrauterine balloon tamponade. © 2014 Wiley Periodicals, Inc.

[Intrauterine infection and the preterm brain: dimensions of aetiology research].

PubMed

Dammann, O

2006-02-01

Perinatal brain damage has a diverse and complex aetiology. Over the past decades, much progress has been made in this research field. In this article, I offer a discussion of seven dimensions of aetiological perinatal brain damage research: (1) hypoxia-ischaemia vs. inflammation; (2) "classic" vs. "remote" intrauterine infection; (3) focal vs. diffuse white matter damage; (4) maternal vs. foetal inflammatory response; (5) clinical vs. experimental data; (6) bacterial vs. viral infection; and (7) preterm vs. term delivery. Despite these complexities, it is hoped that obstetricians, neonatologists, and neuropaediatricians will agree on a perinatal neuroprotective strategy in the near future.

SU-D-BRF-05: A Novel System to Provide Real-Time Image-Guidance for Intrauterine Tandem Insertion and Placement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, M; Fontenot, J

Purpose: To develop a system that provides real-time image-guidance for intrauterine tandem insertion and placement for brachytherapy. Methods: The conceptualized system consists of an intrauterine tandem with a transparent, lensed tip, a flexible miniature fiber optic scope, light source and interface for CCD coupling. The tandem tip was designed to act as a lens providing a wide field-of-view (FOV) with minimal image distortion and focus length appropriate for the application. The system is designed so that once inserted, the image-guidance component of the system can be removed and brachytherapy can be administered without interfering with source transport or disturbing tandemmore » placement. Proof-of-principle studies were conducted to assess the conceptualized system's (1) lens functionality (clarity, focus and FOV) (2) and ability to visualize the cervical os of a female placed in the lithotomy position. Results: A prototype of this device was constructed using a commercial tandem modified to incorporate a transparent tip that internally coupled with a 1.9mm diameter fiber optic cable. The 900mm-long cable terminated at an interface that provided illumination as well as facilitated visualization of patient anatomy on a computer. The system provided a 23mm FOV with a focal length of 1cm and provided clear visualization of the cervix, cervical fornix and cervical os. The optical components of the system are easily removed without perturbing the position of a tandem placed in a common fixation clamp. Conclusion: Clinicians frequently encounter difficulty inserting an intrauterine tandem through the cervical os, circumventing fibrotic tissue or masses within the uterus, and positioning the tandem without perforating the uterus. To mitigate these challenges, we have designed and conducted proof-of- principle studies to discern the utility of a prototype device that provides real-time image-guidance for intrauterine tandem placement using fiber optic components.« less

Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

PubMed Central

Yates, D. T.; Macko, A. R.; Nearing, M.; Chen, X.; Rhoads, R. P.; Limesand, S. W.

2012-01-01

Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization. PMID:22900186

Neonatal overfeeding impairs differentiation potential of mice subcutaneous adipose mesenchymal stem cells.

PubMed

Dias, Isabelle; Salviano, Ísis; Mencalha, André; de Carvalho, Simone Nunes; Thole, Alessandra Alves; Carvalho, Laís; Cortez, Erika; Stumbo, Ana Carolina

2018-04-17

Nutritional changes in the development (intrauterine life and postnatal period) may trigger long-term pathophysiological complications such as obesity and cardiovascular disease. Metabolic programming leads to organs and tissues modifications, including adipose tissue, with increased lipogenesis, production of inflammatory cytokines, and decreased glucose uptake. However, stem cells participation in adipose tissue dysfunctions triggered by overfeeding during lactation has not been elucidated. Therefore, this study was the first to evaluate the effect of metabolic programming on adipose mesenchymal stem cells (ASC) from mice submitted to overfeeding during lactation, using the litter reduction model. Cells were evaluated for proliferation capacity, viability, immunophenotyping, and reactive oxygen species (ROS) production. The content of UCP-2 and PGC1-α was determined by Western Blot. ASC differentiation potential in adipogenic and osteogenic environments was also evaluated, as well the markers of adipogenic differentiation (PPAR-γ and FAB4) and osteogenic differentiation (osteocalcin) by RT-qPCR. Results indicated that neonatal overfeeding does not affect ASC proliferation, ROS production, and viability. However, differentiation potential and proteins related to metabolism were altered. ASC from overfed group presented increased adipogenic differentiation, decreased osteogenic differentiation, and also showed increased PGC1-α protein content and reduced UCP-2 expression. Thus, ASC may be involved with the increased adiposity observed in neonatal overfeeding, and its therapeutic potential may be affected.

Premature delivery due to intrauterine Candida infection that caused neonatal congenital cutaneous candidiasis: a case report.

PubMed

Ito, Fumitake; Okubo, Tomoharu; Yasuo, Tadahiro; Mori, Taisuke; Iwasa, Koichi; Iwasaku, Kazuhiro; Kitawaki, Jo

2013-01-01

Congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature. Neonates having this disease present with systemic skin lesions caused by intrauterine Candida infections. We present a case of threatened premature delivery due to Candida chorioamnionitis, which caused both maternal postpartum endometritis and neonatal congenital cutaneous candidiasis. A 34-year-old woman who was admitted for fetal membrane bulging at 20 weeks of gestation underwent McDonald cervical cerclage. We diagnosed threatened premature delivery due to intrauterine infection; therefore, we terminated the gestation by cesarean section at 24 weeks of gestation. Fungi-like yeast was detected in infantile gastric juice. Histopathological findings of the placenta revealed that Candida albicans mycelium invaded the placenta, chorioamniotic membrane and umbilical cord. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Levonorgestrel-releasing intrauterine system (LNG-IUS 12) for prevention of pregnancy for up to five years.

PubMed

Nelson, Anita L

2017-08-01

A new five-year low dose, smaller-framed, levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 12) has been introduced to complement the currently available systems. Areas Covered: This article will provide an overview of this new intrauterine system - its composition and its mechanisms of action as well as the results of the Phase II and III clinical trials of its efficacy, safety and tolerability. Expert Commentary: This new LNG-IUS 12 provides five-year contraceptive protection a pregnancy rate (less than 1%) in first year of use, which puts it into the top tier with the existing LNG-IUS 20 products; however, the LNG-IUS 12 does not have the high rates of amenorrhea often seen with the higher dose devices. On the other hand, this new IUD shares the smaller frame and narrower insertion tube with the lower dose LNG-IUS 8, but offers longer effective life.

Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma Cells Surface in Comparison to Normal Cells.

PubMed

Bertoni, Ana Paula Santin; de Campos, Rafael Paschoal; Tsao, Marisa; Braganhol, Elizandra; Furlanetto, Tania Weber; Wink, Márcia Rosângela

2018-02-17

The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated the ability of thyroid cancer cells to hydrolyze extracellular ATP generating adenosine, and the expression of ecto-enzymes, as compared to normal cells. We found that normal thyroid derived cells presented a higher ability to hydrolyze ATP and higher mRNA levels for ENTDP1-2, when compared to papillary thyroid carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced an increase in proliferation and migration in PTC derived cells, whose effect was blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73. Taken together, these results showed that thyroid follicular cells have a functional purinergic signaling. The higher expression of CD73 in PTC derived cells might favor the accumulation of extracellular adenosine in the tumor microenvironment, which could promote tumor progression. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for thyroid cancer management and treatment.

The levonorgestrel-releasing intrauterine device potentiates stress reactivity.

PubMed

Aleknaviciute, Jurate; Tulen, Joke H M; De Rijke, Yolanda B; Bouwkamp, Christian G; van der Kroeg, Mark; Timmermans, Mirjam; Wester, Vincent L; Bergink, Veerle; Hoogendijk, Witte J G; Tiemeier, Henning; van Rossum, Elisabeth F C; Kooiman, Cornelis G; Kushner, Steven A

2017-06-01

The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability. We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure. Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (P<0.0001). Heart rate was significantly potentiated during the TSST in women using LNG-IUD (P=0.047). In response to ACTH challenge, women using LNG-IUD and EE30/LNG had a blunted salivary cortisol response, compared to NC (P<0.0001). Women using LNG-IUD had significantly elevated levels of hair cortisol compared to EE30/LNG or NC (P<0.0001). Our findings suggest that LNG-IUD contraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sexual differentiation of the copulatory neuromuscular system in green anoles (Anolis carolinensis): normal ontogeny and manipulation of steroid hormones.

PubMed

Holmes, Melissa M; Wade, Juli

2005-09-05

The copulatory neuromuscular system of green anoles is sexually dimorphic and differentiates during embryonic development, although details of the process were unknown. In Experiment 1, we determined the time course of normal ontogeny. Both male and female embryos possessed bilateral copulatory organs (hemipenes) and associated muscles until incubation day 13; the structures completely regressed in female embryos by incubation day 19 (total incubation 34 days). In Experiment 2, we treated eggs with testosterone, dihydrotestosterone, estradiol, or vehicle on both incubation days 10 and 13 to determine whether these steroid hormones mediate sexual differentiation. These time points fall between gonadal differentiation, which was determined in Experiment 1 to complete before day 10, and regression of the peripheral copulatory system in females. Tissue was collected on the day of hatching. Gonads were classified as testes or ovaries; presence versus absence of hemipenes and muscles, and the number and size of copulatory motoneurons were determined. Copulatory system morphology of vehicle-treated animals matched their gonadal sex. Hemipenes and muscles were absent in estradiol-treated animals, and androgens rescued the hemipenes and muscles in most females. Both testosterone and dihydrotestosterone treatment also caused hypertrophy of the hemipenes, which were everted in animals treated with these steroids. Copulatory motoneurons, assessed on the day of hatching in both experiments, were not dimorphic in size or number. Steroid treatment significantly increased motoneuron size and number overall, but no significant differences were detected in pairwise comparisons. These data demonstrate that differentiation of peripheral copulatory neuromuscular structures occurs during embryonic development and is influenced by gonadal steroids (regression by estradiol and enhancement by androgens), but associated motoneurons do not differentiate until later in life.

Maternal predictors of intrauterine growth restriction.

PubMed

Cetin, Irene; Mandò, Chiara; Calabrese, Stefania

2013-05-01

Intrauterine growth restriction (IUGR) occurs when fetal growth rate falls below the genetic potential and affects a significant number of pregnancies, but still no therapy has been developed for this pregnancy disease. This article reviews the most recent findings concerning maternal characteristics and behaviours predisposing to IUGR as well as maternal early markers of the disease. A comprehensive understanding of factors associated with IUGR will help in providing important tools for preventing and understanding adverse outcomes. Maternal nutritional status, diet and exposure to environmental factors are increasingly acknowledged as potential factors affecting fetal growth both by altering nutrient availability to the fetus and by modulating placental gene expression, thus modifying placental function. Assessing nutritional and environmental factors associated with IUGR, and the molecular mechanisms by which they may have a role in the disease onset, is necessary to provide comprehensive and common guidelines for maternal care and recommended behaviours. Moreover, maternal genetic predispositions and early serum markers may allow a better and more specific monitoring of high risk pregnancies, optimizing the timing of delivery.

Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/ intracytoplasmic sperm injection: A randomized clinical trial

PubMed Central

Zarei, Afsoon; Parsanezhad, Mohammad Ebrahim; Younesi, Masoumeh; Alborzi, Saeed; Zolghadri, Jaleh; Samsami, Alamtaj; Amooee, Sedigheh; Aramesh, Shahintaj

2014-01-01

Background: The direct effect of hCG on the human endometrium was studied several times. Objective: The objectives of this study were to evaluate the effectiveness of intrauterine injection of recombinant human chorionic gonadotropin (rhCG) before embryo transfer (ET). Materials and Methods: In this randomized placebo-controlled clinical trial, a total number of 182 infertile patients undergoing their first in vitro fertilization/ intracytoplasmic sperm injection (IVF-ICSI) cycles were randomly assigned to receive 250μg intrauterine rhCG (n=84) or placebo (n=98) before ET. The implantation and pregnancy rates were compared between groups. Results: Patients who received intrauterine rhCG before ET had significantly higher implantation (36.9% vs. 22.4%; p=0.035), clinical pregnancy rates (34.5% vs. 20.4%; p=0.044) and ongoing pregnancy rate (32.1% vs. 18.4%; p=0.032) when compared to those who received placebo. The abortion (2.4% vs. 2.0%; p=0.929) and ectopic pregnancy rates (1.2% vs. 1.0%; p=0.976) were comparable between groups of rhCG and placebo, respectively. Conclusion: Intrauterine injection of 250μg of rhCG before ET significantly improves the implantation and pregnancy rates in IVF/ICSI cycles. Registration ID in IRCT: IRCT2012121711790N1 This article extracted from fellowship course thesis. (Masoumeh Younesi) PMID:24799855

Differential effects of intrauterine growth restriction on brain structure and development in preterm infants: a magnetic resonance imaging study.

PubMed

Padilla, Nelly; Falcón, Carles; Sanz-Cortés, Magdalena; Figueras, Francesc; Bargallo, Núria; Crispi, Fátima; Eixarch, Elisenda; Arranz, Angela; Botet, Francesc; Gratacós, Eduard

2011-03-25

Previous evidence suggests that preterm newborns with intrauterine growth restriction (IUGR) have specific neurostructural and neurodevelopmental anomalies, but it is unknown whether these effects persist in early childhood. We studied a sample of 18 preterm IUGR, 15 preterm AGA - born between 26 and 34 weeks of gestational age (GA) - and 15 healthy born-term infants. Infants were scanned at 12 months corrected age (CA), in a 3T scanner, without sedation. Analyses were made by automated lobar volumetry and voxel-based morphometry (VBM). The neurodevelopmental outcome was assessed in all subjects at 18 months CA with the Bayley Scale for Infant and Toddler Development, third edition. IUGR infants had reduced relative volumes for the insular and temporal lobes. According to VBM, IUGR infants had bilateral reduced gray matter (GM) in the temporal, parietal, frontal, and insular regions compared with the other groups. IUGR infants had increased white matter (WM) in temporal regions compared to the AGA group and in frontal, parietal, occipital, and insular regions compared to the term group. They also showed decreased WM in the cerebellum and a non-significant trend in the hippocampus compared to term infants. IUGR infants had reduced neurodevelopmental scores, which were positively correlated with GM in various regions. These data suggest that the IUGR induces a distinct brain pattern of structural changes that persist at 1 year of life and are associated with specific developmental difficulties. Copyright © 2011 Elsevier B.V. All rights reserved.

Nonoperative management of atypical endometrial hyperplasia and grade 1 endometrial cancer with the levonorgestrel intrauterine device in medically ill post-menopausal women.

PubMed

Baker, William D; Pierce, Stuart R; Mills, Anne M; Gehrig, Paola A; Duska, Linda R

2017-07-01

To assess the endometrial response rates to treatment with the levonorgestrel intrauterine device in post-menopausal women with atypical hyperplasia/endometrial intraepithelial neoplasia and grade 1 endometrioid (AH/EC) endometrial carcinoma who are not surgical candidates. Chart review was undertaken of patients with AH/EC who underwent levonorgestrel intrauterine device insertion by a gynecologic oncologist within two academic health systems between 2002 and 2013. When available, tissue blocks were evaluated with immunohistochemical staining for progesterone receptor expression. A total of 41 patients received treatment for AH/EC with the levonorgestrel intrauterine device. Follow up sufficient to assess response occurred in 36 women (88%). Complete response was documented in 18 of 36 women (50%), no response in 8 patients (22%), partial response in 3 women (8%) and progression of disease in 7 patients (19%). Four of 18 patients with complete response (22%) later experienced relapse of hyperplasia or cancer. Four patients (10%) died during the study period: none had evidence of metastatic disease and 1 of the 4 woman died of perioperative complications following hysterectomy for stage I disease. Patients responding to treatment had significantly lower progesterone receptor expression on post-treatment biopsies. Intrauterine levonorgestrel is a viable treatment option for post-menopausal women with AH/EC who are poor candidates for standard surgical management. The response rate in this series is similar to published reports in premenopausal patients and includes cases of disease recurrence following conversion to benign endometrium. Copyright © 2017 Elsevier Inc. All rights reserved.

Levonorgestrel-releasing intrauterine device in the treatment of abnormal uterine bleeding: a 6- and 12-month morphological and clinical follow-up.

PubMed

Palmara, Vittorio; Sturlese, Emanuele; Villari, Daniela; Giacobbe, Valentina; Retto, Annalisa; Santoro, Giuseppe

2013-08-01

Abnormal uterine bleeding is defined as any alteration in the pattern or volume of menstrual blood flow, and it is preferably treated using hysterectomy, endometrial destruction or the levonorgestrel-releasing intrauterine system (Mirena(®) ). Recently, it has been demonstrated that studies of Mirena(®) were generally small and consequently imprecise. Our study was aimed at assessing the effects of a slow-release levonorgestrel (20 μg/day) intrauterine device in fertile and postmenopausal women experiencing abnormal uterine bleeding that did not respond to traditional medical management. A total of 40 women, of whom 24 were of reproductive capacity and 16 were postmenopausal, were enrolled in the trial. Removal of the intrauterine device was required for only 2 of the 24 fertile women and for only 3 of the 16 postmenopausal women. After 6 and 12 months of treatment, the remaining women were clinically evaluated and underwent ultrasound and hysteroscopy using biopsy specimens as a control. The EuroQol Group EQ-5D questionnaire was used for evaluation of quality of life. The device showed good tolerability and efficacy. It resulted in a reduction in the endometrial mucosal thickness with a regression of bleeding and collateral effects, which were more evident after 12 months of treatment. A positive effect of the device on the woman's quality of life was demonstrated. The slow-release levonorgestrel intrauterine device may be a valid therapeutic tool for treating basic symptomatology and increasing quality of life in women with abnormal uterine bleeding. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Global Liver Proteome Analysis Using iTRAQ Reveals AMPK-mTOR-Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets.

PubMed

Long, Baisheng; Yin, Cong; Fan, Qiwen; Yan, Guokai; Wang, Zhichang; Li, Xiuzhi; Chen, Changqing; Yang, Xingya; Liu, Lu; Zheng, Zilong; Shi, Min; Yan, Xianghua

2016-04-01

Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in postnatal life. However, the underlying mechanisms by which IUGR affects fetal liver development and metabolism remain incompletely understood. Here, we applied a high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on the liver of newborn piglets. As a result, we identified 78 differentially expressed proteins in the three biological replicates, including 31 significantly up-regulated proteins and 47 significantly down-regulated proteins. Among them, a majority of differentially expressed proteins were related to nutrient metabolism and mitochondrial function. Additionally, many significantly down-regulated proteins participated in the mTOR signaling pathway and the phagosome maturation signaling pathway. Further analysis suggested that glucose concentration and hepatic glycogen storage were both reduced in IUGR newborn piglets, which may contribute to AMPK activation and mTORC1 inhibition. However, AMPK activation and mTORC1 inhibition failed to induce autophagy in the liver of IUGR neonatal pigs. A possible reason is that PP2Ac, a potential candidate in autophagy regulation, is significantly down-regulated in the liver of IUGR newborn piglets. These findings may provide implications for preventing and treating IUGR in human beings and domestic animals.

TRIENNIAL REPRODUCTION SYMPOSIUM: Environmental programming of reproduction during fetal life: Effects of intrauterine position and the endocrine disrupting chemical bisphenol A.

PubMed

Vom Saal, F S

2016-07-01

During critical periods in fetal life, there is an increased vulnerability to perturbations in endocrine function due to environmental factors. Small shifts in concentrations of hormones that regulate the differentiation of organs, such as estradiol and testosterone, can have permanent effects on morphology, enzymatic activity, and hormone receptors in tissues as well as neurobehavioral effects. These changes can lead to effects throughout life, including impacting the risk for various diseases (referred to as the Developmental Origins of Adult Health and Disease hypothesis). The intrauterine position phenomenon concerns the consequence for fetuses of randomly implanting next to embryos of the same or opposite sex. An intrauterine position next to males vs. females results in small differences in serum testosterone and estradiol during fetal life that are associated with marked effects on life history (such as lifetime fecundity) in both males and females born in litters (mice, rats, gerbils, rabbits, and swine) as well as human twins. Research with mice subsequently demonstrated that a very small experimental change in fetal serum estradiol levels altered organogenesis and caused permanent changes in organ function. Taken together, these findings led to the hypothesis that environmental chemicals that mimic or antagonize hormone action (e.g., endocrine disrupting chemicals) could also be causing harm at very low exposures (the "low dose" hypothesis) within the range of exposure of humans, domesticated animals, and wildlife. There is now extensive evidence from experimental laboratory animals, sheep, and humans that fetal exposure to very low (presumably safe) doses of the endocrine disrupting chemical bisphenol A (BPA), which exhibits estrogenic activity, can cause permanent changes that can increase the risk of a wide array of diseases. The reasons that federal regulatory agencies are ignoring the massive literature showing adverse effects of BPA and other

Fetal Heart Rate Monitoring during Intrauterine Open Surgery for Myelomeningocele Repair.

PubMed

Santana, Eduardo Félix Martins; Moron, Antônio Fernandes; Barbosa, Maurício Mendes; Milani, Herbene Jose Figuinha; Sarmento, Stephanno Gomes Pereira; Araujo Júnior, Edward; Rolo, Liliam Cristine; Cavalheiro, Sérgio

2016-01-01

The aim of this study was to assess fetal hemodynamics during intrauterine open surgery for myelomeningocele (MMC) repair by describing fetal heart rate (FHR) monitoring in detail related to each part of the procedure. A study was performed with 57 fetuses submitted to intrauterine MMC repair between the 24th and 27th week of gestation. Evaluations of FHR were made in specific periods: before anesthesia, after anesthesia, at the beginning of laparotomy, during uterus abdominal withdrawal, hysterotomy, neurosurgery (before incision, during early skin manipulation, spinal cord releasing, and at the end of neurosurgery), abdominal cavity reintroduction, and abdominal closure, and at the end of surgery. Means ± standard deviations of FHR were established for each period, and analysis of variance with repeated measures was used to assess differences between these periods. The mean differences were assessed with 95% confidence intervals and were analyzed by Tukey's multiple comparison test. The mean FHR during the specific periods mentioned above was 140.2, 140, 139.2, 138.8, 135.1, 133.9, 123.1, 134.0, 134.5, 137.9, and 139.9 bpm, respectively (p < 0.0001). Comparing the different periods, the highest frequencies were observed in the initial and final moments. The neurosurgery stage presents lower frequencies, especially during the release of the spinal cord. FHR monitoring revealed interesting findings in terms of physiological fetal changes during MMC repair, especially during neurosurgery, which was the most critical period. © 2015 S. Karger AG, Basel.

Dietary supplementation with β-hydroxy-β-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

PubMed

Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De

2016-04-01

Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

Intra-uterine contraceptive devices.

PubMed

Elias, J

1985-05-01

Among the advantages of IUDs are the device's high continuation rate, the lack of systemic side effects, and the absence of a need for continual motivation to practice contraception. The effectiveness of plastic IUDs is directly proportional to their surface area, but the degree of excessive bleeding experienced is inversely related to device size. Thus, devices represent a compromise between large size for effectiveness and small size for acceptability. The optimum time to fit an IUD is during the 1st hald of the menstrual cycle. Absolute contraindications to IUD use include the presence of active pelvic inflammatory disease, undiagnosed irregular bleeding, a history of ectopic pregnancy or tubal surgery, and a distorted uteine cavity. Failure rates associated with IUD use range from 2-3% in the 1st year and then decrease. Since the main mechanism of action appears to be production of a sterile inflammatory reaction in the uterine cavity, the IUD prevents intrauterine pregnancy more effectively than ectopic pregnancy. Nonetheless, there is little evidence to suggest that IUD use actually increases the incidence of ectopic pregnancy. Resumption of fertility after IUD removal is not delayed. There is not need to change inert plastic IUDs in women who remain symptom free. The copper devices should be changed every 3-4 years. A search is under way for antifertility agents that can be incorporated into the device to reduce side effects. In general, the IUD is most suitable for older, parous women.

Follicular localization of growth differentiation factor 8 and its receptors in normal and polycystic ovary syndrome ovaries.

PubMed

Lin, Ting-Ting; Chang, Hsun-Ming; Hu, Xiao-Ling; Leung, Peter C K; Zhu, Yi-Min

2018-05-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and its etiology has not been characterized. Growth differentiation factor 8 (GDF8) is a member of the transforming growth factor-β superfamily that plays a critical role in the regulation of ovarian functions. However, the expression pattern of GDF8 in the human ovary is not yet clear. This study examined the cellular distribution of GDF8 and its putative cellular receptors (ACVR2A, ACVR2B, and ALK5) in a series of normal (n = 34) and PCOS ovaries (n = 14). The immunostaining of GDF8, ACVR2A, ACVR2B, and ALK5 was detected in the oocytes regardless of the developmental stage. All these proteins were localized in antral follicles in normal and PCOS ovaries, and the expression of these proteins increased with increasing follicle diameter. A significantly higher expression of GDF8 was detected in the granulosa cells than in the matched theca cells (TCs). These proteins were also localized in the luteal cells of the corpus luteum. Granulosa cells and TCs of large antral follicles in PCOS ovaries display a higher expression of these proteins. The higher expression levels of GDF8 and its functional receptors (ACVR2A, ACVR2B, and ALK5) in antral follicles of PCOS ovaries than those in normal ovaries suggest the possible involvement of dysregulated GDF8 in the pathogenesis of PCOS.

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among

Introduction of the levonorgestrel intrauterine system in Kenya through mobile outreach: review of service statistics and provider perspectives.

PubMed

Hubacher, David; Akora, Vitalis; Masaba, Rose; Chen, Mario; Veena, Valentine

2014-02-01

The levonorgestrel intrauterine system (LNG IUS) was developed over 30 years ago, but the product is currently too expensive for widespread use in many developing countries. In Kenya, one organization has received donated commodities for 5 years, providing an opportunity to assess impact and potential future role of the product. We reviewed service statistics on insertions of the LNG IUS, copper intrauterine device (IUD), and subdermal implant from 15 mobile outreach teams during the 2011 calendar year. To determine the impact of the LNG IUS introduction, we analyzed changes in uptake and distribution of the copper IUD and subdermal implant by comparing periods of time when the LNG IUS was available with periods when it was not available. In addition, we interviewed 27 clinicians to assess their views of the product and of its future role. When the LNG IUS was not available, intrauterine contraception accounted for 39% of long-acting method provision. The addition of the LNG IUS created a slight rise in intrauterine contraception uptake (to 44%) at the expense of the subdermal implant, but the change was only marginally significant (P = .08) and was largely attributable to the copper IUD. All interviewed providers felt that the LNG IUS would increase uptake of long-acting methods, and 70% felt that the noncontraceptive benefits of the product are important to clients. The LNG IUS was well-received among providers and family planning clients in this population in Kenya. Although important changes in service statistics were not apparent from this analysis (perhaps due to the small quantity of LNG IUS that was available), provider enthusiasm for the product was high. This finding, above all, suggests that a larger-scale introduction effort would have strong support from providers and thus increase the chances of success. Adding another proven and highly acceptable long-acting contraceptive technology to the method mix could have important reproductive health

Empty-bladder (hysterographic) view on US for evaluation of intrauterine devices. Work in progress.

PubMed

Carroll, R; Gombergh, R

1987-06-01

Ultrasound scanning of the pelvis with an empty bladder permits a true frontal view of the uterus to be easily obtained. This view is comparable to the en face view seen at hysterography performed with contrast material. Good definition both of the endometrium and the uterine wall makes this the optimal method for the evaluation of an intrauterine contraceptive device.

Diffusion-weighted magnetic resonance imaging of the fetal brain in intrauterine growth restriction.

PubMed

Arthurs, O J; Rega, A; Guimiot, F; Belarbi, N; Rosenblatt, J; Biran, V; Elmaleh, M; Sebag, G; Alison, M

2017-07-01

Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive method for assessing brain maturation and detecting brain lesions, providing apparent diffusion coefficient (ADC) values as a measure of water diffusion. Abnormal ADC values are seen in ischemic brain lesions, such as those associated with acute or chronic hypoxia. The aim of this study was to assess whether ADC values in the fetal brain were different in fetuses with severe intrauterine growth restriction (IUGR) compared with normal controls. Brain magnetic resonance imaging (MRI) with single-shot axial DWI (b = 0 and b = 700 s/mm 2 ) was performed in 30 fetuses with severe IUGR (estimated fetal weight < 3 rd centile with absent or reversed umbilical artery Doppler flow) and in 24 normal controls of similar gestational age. Brain morphology and biometry were analyzed. ADC values were measured in frontal and occipital white matter, centrum semiovale, thalami, cerebellar hemisphere and pons. Frontal-occipital and frontal-cerebellar ADC ratios were calculated, and values were compared between IUGR fetuses and controls. There was no difference in gestational age at MRI between IUGR and control fetuses (IUGR, 30.2 ± 1.6 weeks vs controls, 30.7 ± 1.4 weeks). Fetal brain morphology and signals were normal in all fetuses. Brain dimensions (supratentorial ± infratentorial) were decreased (Z-score, < -2) in 20 (66.7%) IUGR fetuses. Compared with controls, IUGR fetuses had significantly lower ADC values in frontal white matter (1.97 ± 0.23 vs 2.17 ± 0.22 × 10 -3 mm 2 /s; P < 0.0001), thalami (1.04 ± 0.15 vs 1.13 ± 0.10 ×10 -3 mm 2 /s; P = 0.0002), centrum semiovale (1.86 ± 0.22 vs 1.97 ± 0.23 ×10 -3 mm 2 /s; P = 0.01) and pons (0.85 ± 0.19 vs 0.94 ± 0.12 ×10 -3 mm 2 /s; P = 0.043). IUGR fetuses had a lower frontal-occipital ADC ratio than did normal fetuses (1.00 ± 0.11 vs 1.08 ± 0.05; P = 0.003). ADC values in IUGR fetuses were significantly lower than in

Ultrasound predictors of mortality in monochorionic twins with selective intrauterine growth restriction.

PubMed

Ishii, K; Murakoshi, T; Hayashi, S; Saito, M; Sago, H; Takahashi, Y; Sumie, M; Nakata, M; Matsushita, M; Shinno, T; Naruse, H; Torii, Y

2011-01-01

The aim of this study was to evaluate the use of ultrasound assessment to predict risk of mortality in expectantly managed monochorionic twin fetuses with selective intrauterine growth restriction (sIUGR). This was a retrospective study of 101 monochorionic twin pregnancies diagnosed with sIUGR before 26 weeks of gestation. All patients were under expectant management during the observation period. At the initial evaluation, the presence or absence of each of the following abnormalities was documented: oligohydramnios; stuck twin phenomenon; severe IUGR < 3(rd) centile of estimated fetal weight; abnormal Doppler in the umbilical artery; and polyhydramnios in the larger twin. The relationships between these ultrasound findings and mortality of sIUGR fetuses were evaluated using multiple logistic regression analysis. Of 101 sIUGR twins, 22 (21.8%) fetuses suffered intrauterine demise and nine (8.9%) suffered neonatal death; 70 (69.3%) survived the neonatal period. Multiple logistic regression analysis revealed that the stuck twin phenomenon (odds ratio (OR): 14.5; 95% CI: 2.2-93.2; P = 0.006) and constantly absent diastolic flow in the umbilical artery (OR: 29.4; 95% CI: 3.3-264.0; P = 0.003) were significant risk factors for mortality. Not only abnormal Doppler flow in the umbilical artery but also severe oligohydramnios should be recognized as important indicators for mortality in monochorionic twins with sIUGR.

Differential hippocampal protein expression between normal aged rats and aged rats with postoperative cognitive dysfunction: A proteomic analysis.

PubMed

Li, Yang; Wang, Saiying; Ran, Ke; Hu, Zhonghua; Liu, Zhaoqian; Duan, Kaiming

2015-08-01

The aim of the present study was to investigate the differences in the expression of hippocampal proteins between normal control aged rats and aged rats with postoperative cognitive dysfunction (POCD). A total of 24 aged rats were randomly divided into a surgery group (n=12) and a control group (n=12). The rats in the surgery group were treated with 2 h isoflurane anesthesia and splenectomy, while the rats in the control group received 40% oxygen for 2 h without surgery. The cognitive functions of the two groups were examined using a Y-maze test. The protein expression profiles of the hippocampus of six aged rats (three rats with POCD and three from the normal control group) were assessed using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. A total of three differential proteins were further confirmed between the POCD rats and normal rats using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The expression levels of 21 proteins in the rats with POCD were significantly different compared with the normal control rats. These proteins were functionally clustered to synaptic plasticity (three proteins), oxidative stress (four proteins), energy production (six proteins), neuroinflammation (three proteins) and glutamate metabolism (two proteins). In addition, three proteins (fatty acid binding protein 7, brain, glutamate dehydrogenase 1 and glutamine synthetase), associated with astrocytic function, were significantly different in the rats with POCD compared with those in the normal control (P<0.05). Similar changes in the mRNA expression levels of the three proteins in the hippocampi of POCD rats were also detected using RT-qPCR. Neuroinflammation, glutamate toxicity and oxidative stress were possibly involved in the pathological mechanism underlying POCD in aged rats. In addition, astrocytes may also be important in POCD in aged rats.

Optimal consistency in microRNA expression analysis using reference-gene-based normalization.

PubMed

Wang, Xi; Gardiner, Erin J; Cairns, Murray J

2015-05-01

Normalization of high-throughput molecular expression profiles secures differential expression analysis between samples of different phenotypes or biological conditions, and facilitates comparison between experimental batches. While the same general principles apply to microRNA (miRNA) normalization, there is mounting evidence that global shifts in their expression patterns occur in specific circumstances, which pose a challenge for normalizing miRNA expression data. As an alternative to global normalization, which has the propensity to flatten large trends, normalization against constitutively expressed reference genes presents an advantage through their relative independence. Here we investigated the performance of reference-gene-based (RGB) normalization for differential miRNA expression analysis of microarray expression data, and compared the results with other normalization methods, including: quantile, variance stabilization, robust spline, simple scaling, rank invariant, and Loess regression. The comparative analyses were executed using miRNA expression in tissue samples derived from subjects with schizophrenia and non-psychiatric controls. We proposed a consistency criterion for evaluating methods by examining the overlapping of differentially expressed miRNAs detected using different partitions of the whole data. Based on this criterion, we found that RGB normalization generally outperformed global normalization methods. Thus we recommend the application of RGB normalization for miRNA expression data sets, and believe that this will yield a more consistent and useful readout of differentially expressed miRNAs, particularly in biological conditions characterized by large shifts in miRNA expression.

Effects of intrauterine infusion of Escherichia coli lipopolysaccharide on uterine health, resolution of purulent vaginal discharge, and reproductive performance of lactating dairy cows.

PubMed

Moraes, João G N; Silva, Paula R B; Mendonça, Luís G D; Scanavez, Alexandre A; Silva, Joseane C C; Chebel, Ricardo C

2017-06-01

The objectives of the current experiment were to evaluate the effects of intrauterine infusion of Escherichia coli lipopolysaccharide (LPS) in cows diagnosed with purulent vaginal discharge (PVD) on intrauterine cell population, resolution of PVD, uterine health, and reproductive performance. Jersey cows (n = 3,084) were examined using the Metricheck device to diagnose PVD at 35 ± 6 d postpartum. Purulent vaginal discharge was defined as the presence of purulent (≥50% pus) discharge detectable in the vagina. Of the 310 cows positive for PVD, 267 cows were enrolled in the current experiment. To ensure proper timing of treatment and collection of samples, only 9 PVD-positive cows were treated per day. Selected cows were balanced at 35 ± 6 d postpartum for lactation number, body condition score, and milk yield and were randomly assigned to receive an intrauterine infusion of 20 mL of phosphate-buffered saline (PBS; control, n = 87), 20 mL of PBS with 150 µg LPS (LPS150, n = 91), or 20 mL of PBS with 300 µg of LPS (LPS300, n = 89). Uterine cytology was performed immediately before treatment and 1, 2, and 7 d after treatment to evaluate the effect of LPS treatment on intrauterine cell population. Cows were examined with the Metricheck device at 7 and 28 d after treatment to evaluate the effects of treatment on resolution of PVD. Reproductive status was recorded up to 200 d postpartum. Cows diagnosed with PVD had greater incidence of twinning, dystocia, retained placenta, and metritis after calving than cows without PVD. Count of polymorphonuclear leukocytes (PMNL) in uterine cytology 1, 2, and 7 d after intrauterine infusion was not statistically different among treatments. From d 0 to 1, however, PMNL count in uterine cytology of PBS cows increased by 5%, whereas the PMNL count in uterine cytology of LPS150 and LPS300 cows increased by 54 and 48%, respectively. Treatment did not affect the likelihood of cows being diagnosed with PVD 7 and 28 d after intrauterine

Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.

PubMed

Vázquez-Gómez, M; Valent, D; García-Contreras, C; Arroyo, L; Óvilo, C; Isabel, B; Bassols, A; González-Bulnes, A

2016-12-01

The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction.

PubMed

Gatford, Kathryn L; Kaur, Gunveen; Falcão-Tebas, Filippe; Wadley, Glenn D; Wlodek, Mary E; Laker, Rhianna C; Ebeling, Peter R; McConell, Glenn K

2014-05-01

Individuals born after intrauterine growth restriction (IUGR) are at an increased risk of developing diabetes in their adult life. IUGR impairs β-cell function and reduces β-cell mass, thereby diminishing insulin secretion. IUGR also induces insulin resistance, with impaired insulin signaling in muscle in adult humans who were small for gestational age (SGA) and in rodent models of IUGR. There is epidemiological evidence in humans that exercise in adults can reduce the risk of metabolic disease following IUGR. However, it is not clear whether adult IUGR individuals benefit to the same extent from exercise as do normal-birth-weight individuals, as our rat studies suggest less of a benefit in those born IUGR. Importantly, however, there is some evidence from studies in rats that exercise in early life might be able to reverse or reprogram the long-term metabolic effects of IUGR. Studies are needed to address gaps in current knowledge, including determining the mechanisms involved in the reprogramming effects of early exercise in rats, whether exercise early in life or in adulthood has similar beneficial metabolic effects in larger animal models in which insulin resistance develops after IUGR. Human studies are also needed to determine whether exercise training improves insulin secretion and insulin sensitivity to the same extent in IUGR adults as in control populations. Such investigations will have implications for customizing the recommended level and timing of exercise to improve metabolic health after IUGR.

Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

PubMed

Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

2011-09-01

Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

Long Non-Coding RNAs Differentially Expressed between Normal versus Primary Breast Tumor Tissues Disclose Converse Changes to Breast Cancer-Related Protein-Coding Genes

PubMed Central

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U.; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N.; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O.

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the

Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

PubMed

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the

Differentiation of Normal and Malignant Breast Tissues using Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Mehrotra, Ranjana; Jangir, Deepak Kumar; Gupta, Alka; Kandpal, H. C.

2008-11-01

Infrared spectra of carcinomatous and their normal fore bearing tissues were collected in the 600 cm-1 to 4000 cm-1 region. Fourier Transform Infrared (FTIR) data of infiltrating ductal carcinoma of breast with different grades of malignancy from patients of different age groups were analyzed. Infrared spectra demonstrate significant spectral differences between the tumor sections of normal and the malignant breast tissues. In particular, changes in frequency and intensity in the spectra of protein, nucleic acid and glycogen were observed. This allows to make a qualitative and semi quantitative evaluation of the changes in proliferation activities from normal to diseased tissue. The findings establish a framework for additional studies, which may enable us to establish a relation of the diseased state with its infrared spectra.

New intrauterine technologies for contraception and treatment in -nulliparous/adolescent and parous women.

PubMed

Wildemeersch, D

2009-01-01

The IUD (intra uterine device) is a highly effective method of contraception that is underused. New developments in intrauterine technology, smaller frameless copper and levonorgestrel-releasing devices, could help increase the prevalence-- of use in adolescents and nulliparous women. Because adolescents and young nulliparous women contribute disproportionately to the epidemic of unintended pregnancies, long-acting methods of contraception, particularly IUDs, should be considered as first-line choices for interval, emergency and immediate post-abortal contraception in this population of women. As the uterine cavity is generally much smaller in this group than in older women, adapted IUDs may be very useful. Compatibility of the IUD with the small uterine cavity leads to high acceptability and continuation of use, a prerequisite to reduce unintended pregnancies. A strategic advantage of IUDs is that, unlike the Pill, they are genuinely 'fit-and-forget'. In use, they are much more effective than Pills in this age group. However, copper intrauterine devices do not offer protection against sexually transmitted infections (STIs) and, therefore, they are not always the methods of first choice for teenagers and nulliparous women. New evidence, however, from the World Health -Organization and the American College of Obstetricians and Gynecologists, shows that IUDs can be used and that they are safe for most women, including adolescents.

School-age effects of the newborn individualized developmental care and assessment program for preterm infants with intrauterine growth restriction: preliminary findings.

PubMed

McAnulty, Gloria; Duffy, Frank H; Kosta, Sandra; Weisenfeld, Neil I; Warfield, Simon K; Butler, Samantha C; Alidoost, Moona; Bernstein, Jane Holmes; Robertson, Richard; Zurakowski, David; Als, Heidelise

2013-02-19

The experience in the newborn intensive care nursery results in premature infants' neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother's intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks' lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore, executive function, spectral coherence

Provision of intrauterine contraception in association with first trimester induced abortion reduces the need of repeat abortion: first-year results of a randomized controlled trial.

PubMed

Pohjoranta, Elina; Mentula, Maarit; Gissler, Mika; Suhonen, Satu; Heikinheimo, Oskari

2015-11-01

Can the need of subsequent abortion be reduced by providing intrauterine contraception as a part of the abortion service? Provision of intrauterine devices (IUDs) in association with first trimester abortion more than halved the incidence of repeat abortion during the first year of follow-up. Following abortion, the incidence of subsequent abortion is high, up to 30-40%. In cohort studies, intrauterine contraception has reduced the need of repeat abortion by 60-70%. A randomized controlled trial. The main outcome measure was the incidence of subsequent induced abortions during the follow-up. Altogether 751 women seeking first trimester induced abortion were recruited and randomized into two groups. Randomization was accomplished by computer-assisted permuted-block randomization with random block sizes of four to six. The investigators did not participate in randomization, which was done before commencing the study. The participants were recruited between 18 October 2010 and 21 January 2013. The inclusion criteria were age ≥18 years, duration of pregnancy ≤12 weeks, accepting intrauterine contraception, residence in Helsinki and signing the informed consent form. Women with contraindications to intrauterine contraception, such as uterine anomaly, acute genital infection or pap-smear change requiring surgical treatment were ineligible to participate.This study was conducted in collaboration between the Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, and Centralized family planning of the City of Helsinki.The intervention group (n = 375) was provided with intrauterine contraception (either the levonorgestrel-releasing intrauterine system or copper-releasing intrauterine device) immediately following surgical abortion (18.1%) or at a follow-up 2-4 weeks after medical abortion (81.9%). Women in the control group were prescribed oral contraceptives and advised to contact their primary healthcare unit for a follow

Neurological and neurocognitive functions from intrauterine methylmercury exposure.

PubMed

Yorifuji, Takashi; Kado, Yoko; Diez, Midory Higa; Kishikawa, Toshihiro; Sanada, Satoshi

2016-05-03

In the 1950s, large-scale food poisoning caused by methylmercury was identified in Minamata, Japan. Although severe intrauterine exposure cases (ie, congenital Minamata disease patients) are well known, possible impacts of methylmercury exposure in utero among residents, which is likely at lower levels than in congenital Minamata disease patients, are rarely explored. In 2014, the authors examined neurological and neurocognitive functions among 18 exposed participants in Minamata, focusing on fine motor, visuospatial construction, and executive functions. More than half of the participants had some fine motor and coordination difficulties. In addition, several participants had lower performance for neurocognitive function tests (the Rey-Osterrieth Complex Figure test and Keio version of the Wisconsin card sorting test). These deficits imply diffuse brain damage. This study suggests possible neurological and neurocognitive impacts of prenatal exposure to methylmercury among exposed residents of Minamata.

Cell proliferation in normal epidermis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinstein, G.D.; McCullough, J.L.; Ross, P.

1984-06-01

A detailed examination of cell proliferation kinetics in normal human epidermis is presented. Using tritiated thymidine with autoradiographic techniques, proliferative and differentiated cell kinetics are defined and interrelated. The proliferative compartment of normal epidermis has a cell cycle duration (Tc) of 311 h derived from 3 components: the germinative labeling index (LI), the duration of DNA synthesis (ts), and the growth fraction (GF). The germinative LI is 2.7% +/- 1.2 and ts is 14 h, the latter obtained from a composite fraction of labeled mitoses curve obtained from 11 normal subjects. The GF obtained from the literature and from humanmore » skin xenografts to nude mice is estimated to be 60%. Normal-appearing epidermis from patients with psoriasis appears to have a higher proliferation rate. The mean LI is 4.2% +/- 0.9, approximately 50% greater than in normal epidermis. Absolute cell kinetic values for this tissue, however, cannot yet be calculated for lack of other information on ts and GF. A kinetic model for epidermal cell renewal in normal epidermis is described that interrelates the rate of birth/entry, transit, and/or loss of keratinocytes in the 3 epidermal compartments: proliferative, viable differentiated (stratum malpighii), and stratum corneum. Expected kinetic homeostasis in the epidermis is confirmed by the very similar ''turnover'' rates in each of the compartments that are, respectively, 1246, 1417, and 1490 cells/day/mm2 surface area. The mean epidermal turnover time of the entire tissue is 39 days. The Tc of 311 h in normal cells in 8-fold longer than the psoriatic Tc of 36 h and is necessary for understanding the hyperproliferative pathophysiologic process in psoriasis.« less

The copper-7 intrauterine contraceptive device: 5-year evaluation.

PubMed Central

Sellors, J. W.

1981-01-01

Over a 5-year period a family practitioner inserted copper-7 (Cu-7 intrauterine contraceptive devices (IUDs) in 134 women. The rates of continued use after 2 years, 53.0% for the women's first IUD and 63.9% for all their IUDs, and of accidental pregnancy, 2.4%, are comparable to those in the literature. However, in this series the rate of expulsion was 0.8%, much lower than that in the literature. Fertility did not appear to be reduced in women who planned to have pregnancies after the device was removed. A carefully scrutinized technique of insertion and conscientious follow-up make the Cu-7 IUD an acceptable form of contraception for many patients in a family practice. PMID:7326653

Temporal proteomic analysis reveals defects in small-intestinal development of porcine fetuses with intrauterine growth restriction.

PubMed

Wang, Xiaoqiu; Lin, Gang; Liu, Chuang; Feng, Cuiping; Zhou, Huaijun; Wang, Taiji; Li, Defa; Wu, Guoyao; Wang, Junjun

2014-07-01

The fetus/neonate with intrauterine growth restriction (IUGR) has a high perinatal mortality and morbidity rate, as well as reduced efficiency for nutrients utilization. Our previous studies showed alterations of intestinal proteome in IUGR piglets both at birth and during the nursing period. Considering the potential long-term impacts of fetal programming and substantial increases in amounts of amniotic fluid nutrients from mid-gestation in pigs, the present study involved IUGR porcine fetuses from days 60 to 110 of gestation (mid to late gestation). We identified 59 differentially expressed proteins in the fetal small intestine that are related to intestinal growth, development and reprogramming. Our results further indicated increased abundances of proteins and enzymes associated with oxidative stress, apoptosis and protein degradation, as well as decreased abundances of proteins that are required for maintenance of cell structure and motility, absorption and transport of nutrients, energy metabolism, and protein synthesis in the fetal gut. Moreover, IUGR from middle to late gestation was associated with reduced expression of intestinal proteins that participate in regulation of gene expression and signal transduction. Collectively, these findings provide the first evidence for altered proteomes in the small intestine of IUGR fetuses, thereby predisposing the gut to metabolic defects during gestation and neonatal periods. Copyright © 2014 Elsevier Inc. All rights reserved.

Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system.

PubMed

Eisenberg, David L; Schreiber, Courtney A; Turok, David K; Teal, Stephanie B; Westhoff, Carolyn L; Creinin, Mitchell D

2015-07-01

To assess 3-year data on the efficacy and safety of a new 52-mg levonorgestrel intrauterine contraceptive (LNG20) designed for up to 7 years use. Nulliparous and parous women aged 16-45 years at enrollment with regular menstrual cycles and requesting contraception were enrolled in an open-label, partially randomized trial to evaluate LNG20. The primary outcome was pregnancy rate for women aged 16-35 years calculated as the Pearl Index. Women aged 36-45 years received LNG20 for safety evaluation only. All participants had in-person or phone follow-up approximately every 3 months during the study. A total of 1600 women aged 16-35 years and 151 women aged 36-45 years agreed to LNG20 placement, including 1011 (57.7%) nulliparous and 438 (25.1%) obese women. Successful placement occurred in 1714 (97.9%) women. Six pregnancies occurred, four of which were ectopic. The Pearl Index for LNG20 was 0.15 (95% CI 0.02-0.55) through Year 1, 0.26 (95% CI 0.10-0.57) through Year 2, and 0.22 (95% CI 0.08-0.49) through Year 3. The cumulative life-table pregnancy rate was 0.55 (95% CI 0.24-1.23) through 3 years. Expulsion was reported in 62 (3.5%) participants, most (50 [80.6%]) during the first year of use. Of women who discontinued LNG20 and desired pregnancy, 86.8% conceived spontaneously within 12 months. Pelvic infection was diagnosed in 10 (0.6%) women. Only 26 (1.5%) LNG20 users discontinued due to bleeding complaints. The LNG20 intrauterine system is highly effective and safe over 3 years of use in nulliparous and parous women. A new 52-mg levonorgestrel-releasing intrauterine system is effective and safe for nulliparous and parous women for at least 3 years. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

FORCED NORMALIZATION: Epilepsy and Psychosis Interaction

PubMed Central

Loganathan, Muruga A.; Enja, Manasa

2015-01-01

Forced normalization is the emergence of psychoses following the establishment of seizure control in an uncontrolled epilepsy patient. Two illustrative clinical vignettes are provided about people with epilepsy that was newly controlled and followed by emergence of a psychosis; symptoms appeared only after attaining ictal control. For recognition and differential diagnosis purposes, understanding forced normalization is important in clinical practice. PMID:26155377

Biological evaluation of the copper/low-density polyethylene nanocomposite intrauterine device.

PubMed

Hu, Li-Xia; He, Jing; Hou, Li; Wang, Hong; Li, Jun; Xie, Changsheng; Duan, Zhuo; Sun, Li-Kui; Wang, Xin; Zhu, Changhong

2013-01-01

Devices and materials intended for clinical applications as medical and implant devices should be evaluated to determine their biocompatibility in physiological systems. This article presents results from cytotoxicity assay of L929 mouse fibroblasts culture, tests for skin irritation, intracutaneous reactivity and sensitization, and material implantation tests for the novel copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD) with potential for future clinical utilization. Cytotoxicity test in vitro was conducted to evaluate the change in morphology, growth and proliferation of cultured L929 mouse fibroblasts, which in vivo examination for skin irritation (n = 6) and intracutaneous reactivity (n = 6) were carried out to explore the irritant behavior in New Zealand White rabbits. Skin sensitization was implemented to evaluate the potential skin sensitizing in Hartley guinea pigs (n = 35). The materials were implanted into the spinal muscle of rabbits (n = 9). The cytotoxicity grade of the nano-Cu/LDPE IUD was 0-1, suggested that the composite was nontoxic or mildly cytotoxic; no irritation reaction and skin sensitization were identified in any animals of specific extracts prepared from the material under test; similarly to the control sides, the inflammatory reaction was observed in the rabbits living tissue of the implanted material in intramuscular implantation assay. They indicated that the novel composite intrauterine device presented potential for this type of application because they meet the requirements of the standard practices recommended for evaluating the biological reactivity. The nano-Cu/LDPE IUD has good biocompatibility, which is biologically safe for the clinical research as a novel contraceptive device.

Verbal Short-Term Memory Span in Children: Long-Term Modality Dependent Effects of Intrauterine Growth Restriction

ERIC Educational Resources Information Center

Geva, R.; Eshel, R.; Leitner, Y.; Fattal-Valevski, A.; Harel, S.

2008-01-01

Background: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. Methods: This long-term, prospective design study…

Readiness and Adjustments to School for Children with Intrauterine Growth Restriction (IUGR): An Extreme Test Case Paradigm

ERIC Educational Resources Information Center

Geva, Ronny; Yosipof, Rina; Eshel, Rina; Leitner, Yael; Valevski, Aviva Fattal; Harel, Shaul

2009-01-01

This long-term, prospective study evaluated repeatedly school readiness and adjustment at kindergarten and first grade of children with extreme intrauterine growth restriction (IUGR; n = 20) in relation to controls (n = 19). Methods included individual testing of cognitive competence, self-perception, motivation, loneliness and academic…

Effective salvage of acute massive uterine bleeding using intrauterine balloon tamponade in a uterine adenomyosis patient on dienogest.

PubMed

Nishino, Kimihiro; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-03-01

We present the case of a 37-year-old nulliparous woman in whom acute massive uterine bleeding during dienogest therapy was successfully treated using intrauterine balloon tamponade. Abnormal uterine bleeding and several cases of profuse bleeding causing severe anemia in association with dienogest therapy have been reported, but this is the first reported case involving hypovolemic shock. While successful control of postpartum hemorrhage with intrauterine balloon tamponade has been well described, applications for non-obstetric bleeding, particularly in the presence of underlying diseases, such as adenomyosis, have only rarely been reported. This procedure can be easily, promptly, and safely implemented without analgesia, anesthesia, or laparotomy; it can be used with a minimally dilated external cervical os or narrow uterine cavity; and it can preserve fertility. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

A systematic evaluation of normalization methods in quantitative label-free proteomics.

PubMed

Välikangas, Tommi; Suomi, Tomi; Elo, Laura L

2018-01-01

To date, mass spectrometry (MS) data remain inherently biased as a result of reasons ranging from sample handling to differences caused by the instrumentation. Normalization is the process that aims to account for the bias and make samples more comparable. The selection of a proper normalization method is a pivotal task for the reliability of the downstream analysis and results. Many normalization methods commonly used in proteomics have been adapted from the DNA microarray techniques. Previous studies comparing normalization methods in proteomics have focused mainly on intragroup variation. In this study, several popular and widely used normalization methods representing different strategies in normalization are evaluated using three spike-in and one experimental mouse label-free proteomic data sets. The normalization methods are evaluated in terms of their ability to reduce variation between technical replicates, their effect on differential expression analysis and their effect on the estimation of logarithmic fold changes. Additionally, we examined whether normalizing the whole data globally or in segments for the differential expression analysis has an effect on the performance of the normalization methods. We found that variance stabilization normalization (Vsn) reduced variation the most between technical replicates in all examined data sets. Vsn also performed consistently well in the differential expression analysis. Linear regression normalization and local regression normalization performed also systematically well. Finally, we discuss the choice of a normalization method and some qualities of a suitable normalization method in the light of the results of our evaluation. © The Author 2016. Published by Oxford University Press.

Structure of a radiate pseudocolony associated with an intrauterine contraceptive device

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Brien, P.K.; Lea, P.J.; Roth-Moyo, L.A.

Transmission electron microscopy of a radiate pseudocolony associated with an intrauterine contraceptive device (IUCD) showed central bundles of extracellular fibers averaging 35 nm in diameter, surrounded by layered mantles of electron-dense, amorphous granular material. No bacterial, viral, or fungal structures were present. X-ray microanalysis revealed copper, sulfur, chloride, iron, and phosphorus; no calcium was found. It is postulated that these structures and histologically identical non-IUCD-associated granules from the female genital tract, as well as similar structures from other body locations, including those reported in colloid cysts of the third ventricle, are of lipofuscin origin.

Intrauterine devices and other forms of contraception: thinking outside the pack.

PubMed

Allen, Caitlin; Kolehmainen, Christine

2015-05-01

A variety of contraception options are available in addition to traditional combined oral contraceptive pills. Newer long-acting reversible contraceptive (LARC) methods such as intrauterine devices and subcutaneous implants are preferred because they do not depend on patient compliance. They are highly effective and appropriate for most women. Female and male sterilization are other effective but they are irreversible and require counseling to minimize regret. The contraceptive injection, patch, and ring do not require daily administration, but their typical efficacy rates are lower than LARC methods and similar to those for combined oral contraceptive pills. Copyright © 2015 Elsevier Inc. All rights reserved.

Normal tubular regeneration and differentiation of the post-ischemic kidney in mice lacking vimentin.

PubMed Central

Terzi, F.; Maunoury, R.; Colucci-Guyon, E.; Babinet, C.; Federici, P.; Briand, P.; Friedlander, G.

1997-01-01

Proliferation and dedifferentiation of tubular cells are the hallmark of early regeneration after renal ischemic injury. Vimentin, a class III intermediate filament expressed only in mesenchymal cells of mature mammals, was shown to be transiently expressed in post-ischemic renal tubular epithelial cells. Vimentin re-expression was interpreted as a marker of cellular dedifferentiation, but its role in tubular regeneration after renal ischemia has also been hypothesized. This role was evaluated in mice bearing a null mutation of the vimentin gene. Expression of vimentin, proliferating cell nuclear antigen (a marker of cellular proliferation), and villin (a marker of differentiated brush-border membranes) was studied in wild-type (Vim+/+), heterozygous (Vim+/-), and homozygous (Vim-/-) mice subjected to transient ischemia of the left kidney. As expected, vimentin was detected by immunohistochemistry at the basal pole of proximal tubular cells from post-ischemic kidney in Vim+/+ and Vim+/- mice from day 2 to day 28. The expression of the reporter gene beta-galactosidase in Vim+/- and Vim-/- mice confirmed the tubular origin of vimentin. No compensatory expression of keratin could be demonstrated in Vim-/- mice. The intensity of proliferating cell nuclear antigen labeling and the pattern of villin expression were comparable in Vim-/-, Vim+/- and Vim+/+ mice at any time of the study. After 60 days, the structure of post-ischemic kidneys in Vim-/- mice was indistinguishable from that of normal non-operated kidneys in Vim+/+ mice. In conclusion, 1) the pattern of post-ischemic proximal tubular cell proliferation, differentiation, and tubular organization was not impaired in mice lacking vimentin and 2) these results suggest that the transient tubular expression of vimentin is not instrumental in tubular regeneration after renal ischemic injury. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 PMID:9094992

Intrauterine myelomeningocele repair: effect on short-term complications of prematurity.

PubMed

Hamdan, A H; Walsh, W; Bruner, J P; Tulipan, N

2004-01-01

To determine whether short-term complications of prematurity are affected by intrauterine myelomeningocele repair. Medical records of the first 100 infants undergoing intrauterine myelomeningocele repair (IUMR) at the Vanderbilt University Medical Center were reviewed. Infants born at <34 weeks' gestation were identified. Two controls were identified for each IUMR infant. Controls were matched for gestational age, sex, birth weight, antenatal steroids, and mode and month of delivery. Development of respiratory distress syndrome, intraventricular hemorrhage, and chronic lung disease and days on ventilator and length of hospital stay were recorded. The results are expressed as mean values and ranges. Comparison of data between groups was performed using the Mann-Whitney U test. Categorical data were compared using the chi-square test and Fisher's exact test. p

A randomized comparison of a novel nitinol-frame low-dose-copper intrauterine contraceptive and a copper T380S intrauterine contraceptive.

PubMed

Reeves, Matthew F; Katz, Bob H; Canela, Juan M; Hathaway, Mark J; Tal, Michael G

2017-06-01

We sought to compare VeraCept (VC175), a novel nitinol intrauterine contraceptive (IUC) with 175 square-mm of copper surface area, to a copper T380S IUC. We enrolled parous women into a randomized subject-blinded comparison of VC175 and a copper T380S in a 2:1 fashion at a single clinic. The primary outcomes were total adverse events and continuation at 12 months. We also examined pain on insertion, ease of placement, expulsion, tolerability and pregnancy. Subjective ratings were on a 5-point Likert scale (0, no pain to 5, worst pain). We followed subjects through 24-month follow-up. We enrolled 300 women with 199 randomized to VC175 and 101 to the T380S. Insertion was successful in 198 subjects for VC175 and 100 for the T380S. Mean age was 25 years (range 18, 41), and median parity was 2 (range 1, 8), with 39% having only had Cesarean deliveries. No subjects developed clinical infection or reported serious adverse events. In the VC175 and T380S groups, mean pain at insertion was 1.4 and 2.4, respectively (p<.01). At the 12-month primary endpoint for VC175 and T380S, respectively, continuation was 84% and 68% (p<.002) with expulsions in 5.0% and 12.0% (p<.05) and removal for pain/bleeding in 3.5% and 17.0% (p<.01). At the 24-month visit for VC175 and T380S, respectively, continuation was 77% and 62% (p<.02 by log-rank). One ectopic pregnancy was identified at the 12-month follow-up in a VC175 user. No other pregnancies were diagnosed. With 297.3 and 132.4 woman-years, pregnancy rates were 0.3 and 0.0 per 100 woman-years for VC175 and T380S, respectively. VC175 resulted in less pain at insertion, fewer expulsions and higher total continuation than the T380S, with similar contraceptive efficacy. VC175 is a promising new intrauterine copper contraceptive on a nitinol frame that warrants further clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

PubMed

Bai, Xiaoxia; Tian, Ting; Wang, Peng; Yang, Xiaofu; Wang, Zhengping; Dong, Minyue

2015-03-01

Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human β-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV. © 2014 Wiley Periodicals, Inc.

Intrauterine endometrial cyst after low uterine incision: A case report with literature review.

PubMed

Yin, Weiyao; Zhang, Jiawen; Xu, Liangzhi; Luo, Li

2018-04-01

During the surgical procedure, endometrial cells can be seeded into the wound edge of the uterine wall, developing into scar endometriosis. Due to the extremely low incidence, estimation of its prevalence is still unavailable. Even rarer might be the scar endometriosis in uterine cavity, to our best knowledge, a situation has not been reported yet. A 37-year-old woman complained of heavier and prolonged menstruation as well as pelvic pain during menses for more than 4 months. An endometrial cyst in diameter of 6 cm in uterine cavity was revealed by transvaginal ultrasound. Her surgical history was significant for 1 caesarean section and 1 abdominal myomectomy through transverse incision of lower uterine segment. Space-occupying lesions in uterine cavity, moderate anemia and scar uterus. The hysteroscopy was performed and a multilocular cyst full of chocolate-like fluid was removed. Pathological examination confirmed endometrial glands in the removed cyst tissue. During the follow-up visits at 1 and 6 months after surgery, the patient denied any special discomfort. Her postoperative transvaginal ultrasound showed an enlarged uterus with no lesion in uterine cavity. To achieve a better surveillance, a 3-year period of follow-up after surgery at a 6-month interval was suggested. Intrauterine endometriosis should be considered in patients of pelvic surgery history with pelvic pain, menstrual disorder, and intrauterine cystic mass.

Endometrial suppression with a new 'frameless' levonorgestrel releasing intrauterine system in perimenopausal and postmenopausal women: a pilot study.

PubMed

Wildemeersch, D; Schacht, E

2000-07-31

A novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), derived from the frameless GyneFix intrauterine device (IUD) is described and the preliminary results in 30 symptomatic climacteric and postmenopausal women are discussed. The treatment with the FibroPlant-LNG intrauterine system (IUS) was instituted to suppress the endometrium during estrogen substitution therapy (EST) to prevent endometrial proliferation and bleeding. The purpose of the study was to evaluate the clinical and ultrasonographic effect of this new intrauterine progestin delivery system. Two dosage forms were tested: the first 11 women received a 3-cm long coaxial fibrous delivery system, delivering approximately 10 microg per day of LNG; the remaining 19 women in the study received a 4-cm long delivery system, delivering approximately 14 microg per day. The calculated duration of release of the two systems is approximately 5 years. Twenty-two women were perimenopausal at the start of the treatment. Women in this study were observed for a duration of at least 1 year. Most postmenopausal women received percutaneous 17beta-estradiol (Oestrogel), 1.5 mg daily on a continuous basis. All postmenopausal women in the two groups reported amenorrhea during the entire study period (up to two and a half years follow-up). Endometrial atrophy in these women was confirmed by vaginal ultrasound examination. Seventeen of the 22 perimenopausal women reported amenorrhea at the first or second follow-up visit at 1 and 3 months following insertion of the IUS, respectively. The remaining had infrequent scanty bloody discharge needing a panty liner, at the most, for protection. There were no complications in this study (e.g. infection, expulsion or perforation). The FibroPlant-LNG IUS was very well tolerated by all the women and no systemic hormonal side effects were reported. There were no removals for medical reasons. The results of this pilot study suggest that the frameless FibroPlant-LNG IUS

Synchronous luminescence spectroscopic characterization of blood elements of normal and patients with cervical cancer

NASA Astrophysics Data System (ADS)

Muthuvelu, K.; Shanmugam, Sivabalan; Koteeswaran, Dornadula; Srinivasan, S.; Venkatesan, P.; Aruna, Prakasarao; Ganesan, Singaravelu

2011-03-01

In this study the diagnostic potential of synchronous luminescence spectroscopy (SLS) technique for the characterization of normal and different pathological condition of cervix viz., moderately differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous cell carcinoma (PDSCC) and well differentiated squamous cell carcinoma (WDSSC). Synchronous fluorescence spectra were measured for 70 abnormal cases and 30 normal subjects. Characteristic, highly resolved peaks and significant spectral differences between normal and MDSCC, PDSCC and WDSCC cervical blood formed elements were obtained. The synchronous luminescence spectra of formed elements of normal and abnormal cervical cancer patients were subjected to statistical analysis. Synchronous luminescence spectroscopy provides 90% sensitivity and 92.6% specificity.

Ex Vivo Bioluminescence Imaging of Late Gestation Ewes Following Intra-uterine Inoculation With Lux-modified Escherichia coli

USDA-ARS?s Scientific Manuscript database

Our objectives were to develop an ovine model for Escherichia coli-induced preterm delivery, and monitor E. coli (lux modified for photonic detection) invasion of the fetal environment—ewes (124 ± 18 d of gestation) received intrauterine inoculations using E. coli-lux as follows: control (n = 5), 1....

Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

PubMed Central

Pinnock, Farena; Parlar, Melissa; Hawco, Colin; Hanford, Lindsay; Hall, Geoffrey B.

2017-01-01

This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ± 10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment. PMID:28348889

Clinical application of Lin's biopsy grasper for intrauterine targeted biopsy and polypectomy during office hysteroscopy.

PubMed

Cheng, Hsin-Yi; Lin, Bao-Liang; Tseng, Jen-Yu; Ueno, Kazunori; Nakada, Sakura

2018-06-01

Hysteroscopy has widely been used for diagnosis of the uterine cavity; however, target biopsy has often been difficult in part to the inherent limitations of ancillary instruments. Lin's biopsy grasper was specifically designed to work in conjunction with a flexible hysteroscope to obtain intrauterine biopsy under transabdominal sonography. Herein, we share our clinical experience in the management of endometrial abnormalities with the use of Lin's biopsy grasper during office-based hysteroscopy. From February 2006 to November 2016, the use of Lin's biopsy grasper for tissue biopsy was attempted on 126 cases. We retrospectively recorded and analyzed the patients' preoperative characteristics and biopsy outcomes to demonstrate the feasibility and efficacy of Lin's biopsy grasper. Out of the one hundred and twenty-six enrolled patients, satisfactory targeted biopsies were achieved; including high diagnostic rate (92.1%, with 116 cases confirmed histologically) and adequate tissue retrieval (77.8%, with 98 cases obtaining optimal specimen volume). All patients tolerated the procedure without analgesics or anesthesia. Diagnostic flexible hysteroscopy combined with the use of Lin's biopsy grasper has proven to be an effective tool for intrauterine evaluation and obtaining tissue sample. Copyright © 2018. Published by Elsevier B.V.

Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

PubMed Central

Mirabelli, Peppino; Di Noto, Rosa; Lo Pardo, Catia; Morabito, Paolo; Abate, Giovanna; Gorrese, Marisa; Raia, Maddalena; Pascariello, Caterina; Scalia, Giulia; Gemei, Marica; Mariotti, Elisabetta; Del Vecchio, Luigi

2008-01-01

Background Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007). The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i) multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii) fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii) detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively). As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a). Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA). Conclusion Our study, comparing surface antigen expression of ALDH+/CD34+, ALDH

Intrauterine Growth Restriction: Hungry for an Answer

PubMed Central

Chu, Alison

2016-01-01

Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID:26889018

Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.

PubMed

Lager, Susanne; Jansson, Thomas; Powell, Theresa L

2014-10-15

Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus. Copyright © 2014 the American Physiological Society.

Patterns of brain structural connectivity differentiate normal weight from overweight subjects

PubMed Central

Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

2015-01-01

Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42

School-age effects of the newborn individualized developmental care and assessment program for preterm infants with intrauterine growth restriction: preliminary findings

PubMed Central

2013-01-01

Background The experience in the newborn intensive care nursery results in premature infants’ neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). Methods Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother’s intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks’ lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. Results Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore

Comparison of the levonorgestrel-releasing intrauterine system, hysterectomy, and endometrial ablation for heavy menstrual bleeding in a decision analysis model.

PubMed

Louie, Michelle; Spencer, Jennifer; Wheeler, Stephanie; Ellis, Victoria; Toubia, Tarek; Schiff, Lauren D; Siedhoff, Matthew T; Moulder, Janelle K

2017-11-01

A better understanding of the relative risks and benefits of common treatment options for abnormal uterine bleeding (AUB) can help providers and patients to make balanced, evidence-based decisions. To provide comparative estimates of clinical outcomes after placement of levonorgestrel-releasing intrauterine system (LNG-IUS), ablation, or hysterectomy for AUB. A PubMED search was done using combinations of search terms related to abnormal uterine bleeding, LNG-IUS, hysterectomy, endometrial ablation, cost-benefit analysis, cost-effectiveness, and quality-adjusted life years. Full articles published in 2006-2016 available in English comparing at least two treatment modalities of interest among women of reproductive age with AUB were included. A decision tree was generated to compare clinical outcomes in a hypothetical cohort of 100 000 premenopausal women with nonmalignant AUB. We evaluated complications, mortality, and treatment outcomes over a 5-year period, calculated cumulative quality-adjusted life years (QALYs), and conducted probabilistic sensitivity analysis. Levonorgestrel-releasing intrauterine system had the highest number of QALYs (406 920), followed by hysterectomy (403 466), non-resectoscopic ablation (399 244), and resectoscopic ablation (395 827). Ablation had more treatment failures and complications than LNG-IUS and hysterectomy. Findings were robust in probabilistic sensitivity analysis. Levonorgestrel-releasing intrauterine system and hysterectomy outperformed endometrial ablation for treatment of AUB. © 2017 International Federation of Gynecology and Obstetrics.

Exploring Trends in Intrauterine Device (IUD) Usage among Women in the United States: A Literature Review

ERIC Educational Resources Information Center

Nobiling, Brandye; Drolet, Judy C.

2012-01-01

Intrauterine devices (IUDs) have not been popular contraceptives in the US for the past 40 years. Recent evidence, however, has shown a slight rebirth in use, from a rate of approximately 2% in 2002 to over 5% in 2008 (Guttmacher Institute, 2010). Empirical evidence is favorable of IUD use in most women, but the still-low usage rate suggests…

Copper intrauterine device for emergency contraception: clinical practice among contraceptive providers.

PubMed

Harper, Cynthia C; Speidel, J Joseph; Drey, Eleanor A; Trussell, James; Blum, Maya; Darney, Philip D

2012-02-01

The copper intrauterine device (IUD) is the most effective emergency contraceptive available but is largely ignored in clinical practice. We examined clinicians' recommendations of the copper IUD for emergency contraception in a setting with few cost obstacles. We conducted a survey among clinicians (n=1,246; response rate 65%) in a California State family planning program, where U.S. Food and Drug Administration-approved contraceptives are available at no cost to low-income women. We used multivariable logistic regression to measure the association of intrauterine contraceptive training and evidence-based knowledge with having recommended the copper IUD for emergency contraception. The large majority of clinicians (85%) never recommended the copper IUD for emergency contraception, and most (93%) required two or more visits for an IUD insertion. Multivariable analyses showed insertion skills were associated with having recommended the copper IUD for emergency contraception, but the most significant factor was evidence-based knowledge of patient selection for IUD use. Clinicians who viewed a wide range of patients as IUD candidates were twice as likely to have recommended the copper IUD for emergency contraception. Although more than 93% of obstetrician-gynecologists were skilled in inserting the copper IUD, they were no more likely to have recommended it for emergency contraception than other physicians or advance practice clinicians. Recommendation of the copper IUD for emergency contraception is rare, despite its high efficacy and long-lasting contraceptive benefits. Recommendation would require clinic flow and scheduling adjustments to allow same-day IUD insertions. Patient-centered and high-quality care for emergency contraception should include a discussion of the most effective method. III.

Social media and the intrauterine device: a YouTube content analysis.

PubMed

Nguyen, Brian T; Allen, Allison J

2018-01-01

YouTube's online archive of video testimonials related to health information are more commonly viewed than those developed by clinicians and professional groups, suggesting the importance of the patient experience to viewers. We specifically sought to examine the accuracy of information on, and projected acceptability of, the intrauterine device (IUD) from these YouTube testimonials. We searched YouTube for videos about individual uploaders' IUD experiences, using the search terms 'intrauterine device', 'IUD', 'Mirena' and 'Paragard'. Given interest in user testimonials, we excluded professional and instructional videos belonging to commercial or non-profit entities. Two reviewers independently analysed the videos using a structured guide, with attention to inaccurate information. Of 86 identified videos, four videos featured clinicians and were excluded; 62 met inclusion criteria. Interrater agreement on IUD portrayal was good (K=0.73). Young (mean age 25, range 19-38, years), white (75%), nulliparous (61%) women primarily uploaded content. Most described placement of the LNG-IUS (65%), were posted within 1 month of insertion (45%), and mentioned side effects (66%) - bleeding, pain, and partner sensation of the strings. About one-third of videos contained inaccurate information (34%) and were thought to project an overall negative experience (30%). Videos portraying IUDs negatively were associated with inaccurate information and/or mention of side effects. While one-third of IUD user testimonials on YouTube contained inaccurate information, the majority of IUD experiences were perceived by our study viewers to be positive. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Biological Evaluation of the Copper/Low-density Polyethylene Nanocomposite Intrauterine Device

PubMed Central

Wang, Hong; Li, Jun; Xie, Changsheng; Duan, Zhuo; Sun, Li-Kui; Wang, Xin; Zhu, Changhong

2013-01-01

Devices and materials intended for clinical applications as medical and implant devices should be evaluated to determine their biocompatibility in physiological systems. This article presents results from cytotoxicity assay of L929 mouse fibroblasts culture, tests for skin irritation, intracutaneous reactivity and sensitization, and material implantation tests for the novel copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD) with potential for future clinical utilization. Cytotoxicity test in vitro was conducted to evaluate the change in morphology, growth and proliferation of cultured L929 mouse fibroblasts, which in vivo examination for skin irritation (n = 6) and intracutaneous reactivity (n = 6) were carried out to explore the irritant behavior in New Zealand White rabbits. Skin sensitization was implemented to evaluate the potential skin sensitizing in Hartley guinea pigs (n = 35). The materials were implanted into the spinal muscle of rabbits (n = 9). The cytotoxicity grade of the nano-Cu/LDPE IUD was 0–1, suggested that the composite was nontoxic or mildly cytotoxic; no irritation reaction and skin sensitization were identified in any animals of specific extracts prepared from the material under test; similarly to the control sides, the inflammatory reaction was observed in the rabbits living tissue of the implanted material in intramuscular implantation assay. They indicated that the novel composite intrauterine device presented potential for this type of application because they meet the requirements of the standard practices recommended for evaluating the biological reactivity. The nano-Cu/LDPE IUD has good biocompatibility, which is biologically safe for the clinical research as a novel contraceptive device. PMID:24058521

Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.

PubMed

Craciunas, Laurentiu; Tsampras, Nikolaos; Coomarasamy, Arri; Raine-Fenning, Nick

2016-05-20

Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction. To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction. We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator. We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin. Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of

[Effects of Fukang oral liquid on the prevention of intrauterine adhesion and expressions of TGF-beta1, PAI-1 and MMP-9 in endometrium of rats].

PubMed

Hu, Sha; Li, Ya; Meng, Wei-Jie; Tan, Shi-Qiao

2013-07-01

To investigate the preventing effect of Fukang oral liquid (fuk) in intrauterine adhesions and its effects on the expression of TGFbeta-1, PAI-1 and MMP-9 in endometrium of rats with intrauterine adhesions. 50 female wistar rats were divided into high, medium, low dose of Fukang oral liquid group (Hfuk, Mfuk, Lfuk), blank control group (Bcon), and model control group (Mcon) (n = 10 in each group). The rats in Hfuk, Mfuk and Lfuk groups were treated with intragastric administration of 4 mL, 2 mL and 1 mL Fukang Oral Liquid per day, while the rats in Mcon group and Bcon group received 2 mL physiological saline intragastric administration per day. All of rats were executed on 10th day and the sample of endometrium was harvested for the study of histology and morphology and the expression of TGFbeta-1, PAI-1 and MMP-9. Under the light microscope, the organizational structure of the uterine cavity and uterine wall was clear in Bcon group, the uterine cavity disappeared in Mcon group, and the layers structure remained normal arrangement in three fuk treated groups. TGFbeta-1 and PAI-1 protein expressions in Hfuk, Mfuk, Lfuk groups were less than those in Mcon group (P < 0.001), but MMP-9 protein expressions were higher. (P < 0.001). Fukang oral liquid show preventing effect on IUA, the mechanism may be related to its effects on the expressions of TGF-beta1, PAI-1, and MMP-9 in the endometrium.

Effects of Choline on Meat Quality and Intramuscular Fat in Intrauterine Growth Retardation Pigs.

PubMed

Li, Bo; Li, Wei; Ahmad, Hussain; Zhang, Lili; Wang, Chao; Wang, Tian

2015-01-01

The aim of this study was to investigate the effects of choline supplementation on intramuscular fat (IMF) and lipid oxidation in IUGR pigs. Twelve normal body weight (NBW) and twelve intrauterine growth retardation (IUGR) newborn piglets were collected and distributed into 4 treatments (Normal: N, Normal+Choline: N+C, IUGR: I, and IUGR+Choline: I+C) with 6 piglets in each treatment. At 23 d of age, NBW and IUGR pigs were fed basal or choline supplemented diets. The results showed that the IUGR pigs had significantly lower (P<0.05) BW as compared with the NBW pigs at 23 d, 73 d, and 120 d of age, however, there was a slight decreased (P>0.05) in BW of IUGR pigs than the NBW pigs at 200 d. Compared with the NBW pigs, pH of meat longissimus dorsi muscle was significantly lower (P<0.05), and the meat color was improved in IUGR pigs. The malondialdehyde (MDA) levels were significantly decreased (P<0.05), while triglyceride (TG) and IMF contents were significantly higher (P<0.05) in the IUGR pigs than the NBW pigs. IUGR up-regulated the mRNA gene expression of fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC). Dietary choline significantly increased (P<0.05) the BW at 120d of age, however, significantly decreased (P<0.05) the TG and IMF contents in both IUGR and NBW pigs. FAS and sterol regulatory element-binding proteins 1 (SREBP1) mRNA gene expressions were increased (P<0.05) while the muscle-carnitine palmityl transferase (M-CPT) and peroxisome proliferators-activated receptorγ (PPARγ) mRNA (P<0.05) gene expressions were decreased in the muscles of the IUGR pigs by choline supplementation. Furthermore, choline supplementation significantly increased (P<0.05) the MDA content as well as the O2•¯ scavenging activity in meat of IUGR pigs. The results suggested that IUGR pigs showed a permanent stunting effect on the growth performance, increased fat deposition and oxidative stress in muscles. However, dietary supplementation of choline improved the fat

Effects of Choline on Meat Quality and Intramuscular Fat in Intrauterine Growth Retardation Pigs

PubMed Central

Li, Bo; Li, Wei; Ahmad, Hussain; Zhang, Lili; Wang, Chao; Wang, Tian

2015-01-01

The aim of this study was to investigate the effects of choline supplementation on intramuscular fat (IMF) and lipid oxidation in IUGR pigs. Twelve normal body weight (NBW) and twelve intrauterine growth retardation (IUGR) newborn piglets were collected and distributed into 4 treatments (Normal: N, Normal+Choline: N+C, IUGR: I, and IUGR+Choline: I+C) with 6 piglets in each treatment. At 23 d of age, NBW and IUGR pigs were fed basal or choline supplemented diets. The results showed that the IUGR pigs had significantly lower (P<0.05) BW as compared with the NBW pigs at 23 d, 73 d, and 120 d of age, however, there was a slight decreased (P>0.05) in BW of IUGR pigs than the NBW pigs at 200 d. Compared with the NBW pigs, pH of meat longissimus dorsi muscle was significantly lower (P<0.05), and the meat color was improved in IUGR pigs. The malondialdehyde (MDA) levels were significantly decreased (P<0.05), while triglyceride (TG) and IMF contents were significantly higher (P<0.05) in the IUGR pigs than the NBW pigs. IUGR up-regulated the mRNA gene expression of fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC). Dietary choline significantly increased (P<0.05) the BW at 120d of age, however, significantly decreased (P<0.05) the TG and IMF contents in both IUGR and NBW pigs. FAS and sterol regulatory element-binding proteins 1 (SREBP1) mRNA gene expressions were increased (P<0.05) while the muscle-carnitine palmityl transferase (M-CPT) and peroxisome proliferators-activated receptorγ (PPARγ) mRNA (P<0.05) gene expressions were decreased in the muscles of the IUGR pigs by choline supplementation. Furthermore, choline supplementation significantly increased (P<0.05) the MDA content as well as the O2•¯ scavenging activity in meat of IUGR pigs. The results suggested that IUGR pigs showed a permanent stunting effect on the growth performance, increased fat deposition and oxidative stress in muscles. However, dietary supplementation of choline improved the fat

NIMROD: a program for inference via a normal approximation of the posterior in models with random effects based on ordinary differential equations.

PubMed

Prague, Mélanie; Commenges, Daniel; Guedj, Jérémie; Drylewicz, Julia; Thiébaut, Rodolphe

2013-08-01

Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mechanism of action of the levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding.

PubMed

Cihangir, Uzunçakmak; Ebru, Akbay; Murat, Ekin; Levent, Yaşar

2013-11-01

To assess the efficacy and adverse effects, and reveal the effective pathway of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of heavy menstrual bleeding. In a prospective single-center study in Istanbul, Turkey, the LNG-IUS was inserted in 60 patients diagnosed with heavy menstrual bleeding between January 2008 and June 2010. Menstrual bleeding pattern, coagulation parameters, uterine arterial blood flow, endometrial thickness, and uterine and ovarian volumes were assessed pre-insertion, and at 6 and 12months. Forty-nine women completed the study. When compared with pre-insertion values, the LNG-IUS led to improvements in hemoglobin and marked decreases in visual bleeding scores, endometrial thickness, and fibrinogen levels (P<0.001); platelet count, international normalized ratio, prothrombin time, activated partial thromboplastin time, and uterine volume also decreased (P<0.05). No significant change in ovarian volumes, or uterine artery resistive and pulsatility indices was observed at 6 or 12months compared with pre-insertion values. The decline in menstrual blood loss among LNG-IUS users was associated with local progestogenic effects and aggravation of intrinsic and extrinsic coagulation pathways. Although the LNG-IUS is a highly effective method for treating heavy menstrual bleeding, care must be taken when a patient has thromboembolic risk factors. © 2013.

Intrauterine myelomeningocele repair postnatal results and follow-up at 3.5 years of age--initial experience from a single reference service in Brazil.

PubMed

Hisaba, Wagner Jou; Cavalheiro, Sérgio; Almodim, Carlos Gilberto; Borges, Carolina Peixoto; de Faria, Tereza Cristina Carbonari; Araujo Júnior, Edward; Nardozza, Luciano Marcondes Machado; Moron, Antonio Fernandes

2012-03-01

Present the outcomes of six cases submitted to intrauterine myelomeningocele (MMC) repair. Descriptive observational study of six children submitted to antenatal surgical repair of MMC between 26 and 27 weeks gestation. All deliveries were through cesarean section. The following neonatal variables were assessed: gestational age at delivery, birth weight, Apgar scores, need for intubation, duration of hospital stay and need for postnatal shunt procedures. After 3.5 years, the children were evaluated using the Columbia Mental Maturity Scale or Denver II tests and the Hoffer Ambulation Scale. All deliveries were preterm at a mean gestational age of 32 + 4 weeks and mean birth weight was 1,942 g. Two infants had Apgar scores <7 at 1 min and 1 at 5 min. Ventricular-peritoneal shunts were placed in two cases. All six children are alive: five have normal cognitive development and one has a neuropsychomotor developmental delay. Two children had normal leg movements, a sacral functional level and are community ambulators. Three children had upper lumbar anatomical level lesions and one had a lower thoracic level lesion at the time of fetal surgery. One child, with an L1-L2 anatomical level lesion, in noambulatory and fully dependent on a wheelchair for mobility. Antenatal surgical repair of MMC reduced the need for postnatal shunt placements. Despite preterm delivery, the cognitive development of most children at 3.5 years was normal. Antenatal surgery seemed to improve lower limb motor function in these cases.

Bilateral oblique facial clefts and extremity anomaly in an infant after intrauterine efavirenz exposure and review of its teratogenic risk.

PubMed

Shanske, Alan L

2012-09-10

Congenital anomalies may be caused by genetic or environmental factors or a combination of both. Oblique facial clefts are very rare congenital deformities. The occurrence of facial clefts and an extremity anomaly suggests a common underlying cause. Lateral oro-ocular clefts do not occur along normal developmental planes and may be part of the amnion disruption complex sequence. Our objective was to report a case of this very event, which also followed an unusual intrauterine exposure and review the literature on the teratogenic risk of efavirenz. We report a case of amniotic rupture sequence after fetal HIV and antiretroviral exposure. Teratogenic exposure has been rarely reported and never after antiretroviral exposure. By reporting and registering more cases, we will be able to better assess the risks such medications pose to the developing fetus. The publication of a single case report has the potential to contribute to our knowledge of the significance of prenatal exposure to antiretrovirals and other medications for common HIV-associated disorders. It also generates a hypothesis that can be tested with further clinical data, animal models and epidemiologic studies.

Genome-wide placental DNA methylation analysis of severely growth-discordant monochorionic twins reveals novel epigenetic targets for intrauterine growth restriction.

PubMed

Roifman, Maian; Choufani, Sanaa; Turinsky, Andrei L; Drewlo, Sascha; Keating, Sarah; Brudno, Michael; Kingdom, John; Weksberg, Rosanna

2016-01-01

Intrauterine growth restriction (IUGR), which refers to reduced fetal growth in the context of placental insufficiency, is etiologically heterogeneous. IUGR is associated not only with perinatal morbidity and mortality but also with adult-onset disorders, such as cardiovascular disease and diabetes, posing a major health burden. Placental epigenetic dysregulation has been proposed as one mechanism that causes IUGR; however, the spectrum of epigenetic pathophysiological mechanisms leading to IUGR remains to be elucidated. Monozygotic monochorionic twins are particularly affected by IUGR, in the setting of severe discordant growth. Because monozygotic twins have the same genotype at conception and a shared maternal environment, they provide an ideal model system for studying epigenetic dysregulation of the placenta. We compared genome-wide placental DNA methylation patterns of severely growth-discordant twins to identify novel candidate genes for IUGR. Snap-frozen placental samples for eight severely growth-discordant monozygotic monochorionic twin pairs were obtained at delivery from each twin. A high-resolution DNA methylation array platform was used to identify methylation differences between IUGR and normal twins. Our analysis revealed differentially methylated regions in the promoters of eight genes: DECR1, ZNF300, DNAJA4, CCL28, LEPR, HSPA1A/L, GSTO1, and GNE. The largest methylation differences between the two groups were in the promoters of DECR1 and ZNF300. The significance of these group differences was independently validated by bisulfite pyrosequencing, implicating aberrations in fatty acid beta oxidation and transcriptional regulation, respectively. Further analysis of the array data identified methylation changes most prominently affecting the Wnt and cadherin pathways in the IUGR cohort. Our results suggest that IUGR in monozygotic twins is associated with impairments in lipid metabolism and transcriptional regulation as well as cadherin and Wnt

Secretagogin is a novel marker for neuroendocrine differentiation.

PubMed

Birkenkamp-Demtröder, Karin; Wagner, Ludwig; Brandt Sørensen, Flemming; Bording Astrup, Lone; Gartner, Wolfgang; Scherübl, Hans; Heine, Bernhard; Christiansen, Peer; Ørntoft, Torben Falck

2005-01-01

Our previous microarray-based studies identified secretagogin to be highly expressed in normal colon mucosa compared to basal expression in colon adenocarcinomas. The aim of this study was to analyze the differential expression of secretagogin in normal mucosa, adenocarcinomas, and neuroendocrine tumors. Western blotting, immunohistochemistry, immunofluorescence microscopy and ELISA were applied. Western blot analysis detected a 32-kDa secretagogin band in samples from normal mucosa. Immunohistochemical analyses on tissue specimens showed that secretagogin is exclusively expressed in neuroendocrine cells and nerve cells in normal mucosa of the digestive tract. Tissues adjacent to benign hyperplasic polyps and adenomas showed a decreased number of secretagogin-expressing neuroendocrine cells. Secretagogin co-localized with neuroendocrine markers (chromogranin A, neuron-specific enolase, synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas and adrenal gland. Secretagogin was detected in plasma from carcinoid patients with distant metastasis. Combined immunohistochemical analysis of secretagogin and FK506-binding protein 65, a protein de novo synthesized in adenocarcinomas, distinguished well-differentiated carcinoids, adenocarcinoids and undifferentiated carcinomas. We conclude that secretagogin is a novel marker for neuroendocrine differentiation.

Perinatal outcome and later implications of intrauterine growth restriction.

PubMed

Pallotto, Eugenia K; Kilbride, Howard W

2006-06-01

This chapter reviews outcomes for children who have intrauterine growth retardation (IUGR) or small-for-gestation-age (SGA) status at birth. Such infants are at risk for increased perinatal mortality, birth adaptation complications, including perinatal acidosis, hypoglycemia, hypothermia, coagulation abnormalities, and selected immunologic deficiencies. IUGR infants also appear to be at great risk for complications of prematurity, including chronic lung disease and necrotizing enterocolitis. Childhood implications for IUGR include an increased risk for short stature, cognitive delays with decreased academic achievement, and a small but significant increased risk of neurologic disorders, including cerebral palsy. Low socioeconomic status is correlated with the occurrence of IUGR and is significantly related to long-term disabilities. Morbidities associated with preterm delivery appear to be additive to those associated with fetal growth restriction so IUGR, preterm infants may be at great risk for poor neurodevelopmental outcome.

Intrauterine Exposure to Methylmercury and Neurocognitive Functions: Minamata Disease.

PubMed

Yorifuji, Takashi; Kato, Tsuguhiko; Kado, Yoko; Tokinobu, Akiko; Yamakawa, Michiyo; Tsuda, Toshihide; Sanada, Satoshi

2015-01-01

A large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s. The severe intrauterine exposure cases are well known, although the possible impact of low-to-moderate methylmercury exposure in utero are rarely investigated. We examined neurocognitive functions among 22 participants in Minamata, mainly using an intelligence quotient test (Wechsler Adults Intelligent Scale III), in 2012/2013. The participants tended to score low on the Index score of processing speed (PS) relative to full-scale IQ, and discrepancies between PS and other scores within each participant were observed. The lower score on PS was due to deficits in digit symbol-coding and symbol search and was associated with methylmercury concentration in umbilical cords. The residents who experienced low-to-moderate methylmercury exposure including prenatal one in Minamata manifested deficits in their cognitive functions, processing speed in particular.

Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts

NASA Technical Reports Server (NTRS)

Winchester, S. K.; Bloch, S. R.; Fiacco, G. J.; Partridge, N. C.

1999-01-01

We investigated the regulation of collagenase-3 expression in normal, differentiating rat osteoblasts. Fetal rat calvarial cell cultures showed an increase in alkaline phosphatase activity reaching maximal levels between 7-14 days post-confluence, then declining with the onset of mineralization. Collagenase-3 mRNA was just detectable after proliferation ceased at day 7, increased up to day 21, and declined at later ages. Postconfluent cells maintained in non-mineralizing medium expressed collagenase-3 but did not show the developmental increase exhibited by cells switched to mineralization medium. Cells maintained in non-mineralizing medium continued to proliferate; cells in mineralization medium ceased proliferation. In addition, collagenase-3 mRNA was not detected in subcultured cells allowed to remineralize. These results suggest that enhanced accumulation of collagenase-3 mRNA is triggered by cessation of proliferation or acquisition of a mineralized extracellular matrix and that other factors may also be required. After initiation of basal expression, parathyroid hormone (PTH) caused a dose-dependent increase in collagenase-3 mRNA. Both the cyclic adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (8-Br-cAMP), and the protein kinase C (PKC) activator, phorbol myristate acetate, increased collagenase-3 expression, while the calcium ionophore, ionomycin, did not, suggesting that PTH was acting through the protein kinase A (PKA) and PKC pathways. Inhibition of protein synthesis with cycloheximide caused an increase in basal collagenase-3 expression but blocked the effect of PTH, suggesting that an inhibitory factor prevents basal expression while an inductive factor is involved with PTH action. In summary, collagenase-3 is expressed in mineralized osteoblasts and cessation of proliferation and initiation of mineralization are triggers for collagenase-3 expression. PTH also stimulates expression of the enzyme through both PKA and PKC pathways in the

A normalization strategy for comparing tag count data

PubMed Central

2012-01-01

Background High-throughput sequencing, such as ribonucleic acid sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, enables various features of organisms to be compared through tag counts. Recent studies have demonstrated that the normalization step for RNA-seq data is critical for a more accurate subsequent analysis of differential gene expression. Development of a more robust normalization method is desirable for identifying the true difference in tag count data. Results We describe a strategy for normalizing tag count data, focusing on RNA-seq. The key concept is to remove data assigned as potential differentially expressed genes (DEGs) before calculating the normalization factor. Several R packages for identifying DEGs are currently available, and each package uses its own normalization method and gene ranking algorithm. We compared a total of eight package combinations: four R packages (edgeR, DESeq, baySeq, and NBPSeq) with their default normalization settings and with our normalization strategy. Many synthetic datasets under various scenarios were evaluated on the basis of the area under the curve (AUC) as a measure for both sensitivity and specificity. We found that packages using our strategy in the data normalization step overall performed well. This result was also observed for a real experimental dataset. Conclusion Our results showed that the elimination of potential DEGs is essential for more accurate normalization of RNA-seq data. The concept of this normalization strategy can widely be applied to other types of tag count data and to microarray data. PMID:22475125

Colonoscopic Removal of an Intrauterine Device That Had Perforated the Rectosigmoid Colon

PubMed Central

Huh, Jin Myeong; Kim, Ki Seok; Cho, Yong Seok; Lee, Jae Uk; Baek, Seong Deuk; Moon, Sin Kil

2018-01-01

The intrauterine device (IUD) is a widely used contraceptive method. One of the most serious and rare complications of using an IUD is colon perforation. We report a case of colonoscopic removal of an IUD that had perforated into the rectosigmoid colon in a 42-year-old woman who presented with no symptoms. Colonoscopy showed that the IUD had penetrated into rectosigmoid colon wall and that an arm of the IUD was embedded in the colon wall. We were able to remove the IUD easily by using colonoscopy. The endoscopic approach may be considered the first choice therapy for selected patients. PMID:29742863

Levonorgestrel-releasing intrauterine device versus dydrogesterone for management of endometrial hyperplasia without atypia.

PubMed

El Behery, Manal M; Saleh, Hend S; Ibrahiem, Moustafa A; Kamal, Ebtesam M; Kassem, Gamal A; Mohamed, Mohamed El Sayed

2015-03-01

To compare the efficacy and safety of the levonorgestrel-releasing intrauterine device (LNG-IUD) with dydrogesterone applied for the same duration in patients having endometrial hyperplasia (EH) without atypia. One hundred thirty eight women aged between 30 and 50 years with abnormal uterine bleeding and diagnosed as EH by transvaginal ultrasound were randomized to receive either LNG-IUD or dydrogesterone for 6 months. Primary outcome measures were regression of hyperplasia after 6 months of therapy. Secondary outcome measures were occurrence of side effects during treatment or recurrence of hyperplasia during follow-up period. After 6 months of treatment, regression of EH occurs in 96% of women in the levonorgestrel-releasing intrauterine system (LNG-IUS) group versus 80% of women in the oral group (P < .001). Adverse effects were relatively common with minimal differences between the 2 groups. Intermenstrual vaginal spotting and amenorrhea were more common in the LNG-IUD group (P value .01 and .0001). Patient satisfaction was significantly higher in the LNG-IUS group (P value .0001). Hysterectomy rates were lower in the LNG-IUS group than in the oral group (P = .001). Recurrence rate was 0% in the LNG-IUD group compared to 12.5% in the oral group. In management of EH without atypia, LNG-IUS achieves a higher regression and a lower hysterectomy rate than oral progesterone and could be used as a first-line therapy. © The Author(s) 2014.

Measurement of normalized differential t\\overline{t} cross sections in the dilepton channel from pp collisions at √{s}=13 TeV

NASA Astrophysics Data System (ADS)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Strauss, J.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Janssen, X.; Lauwers, J.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lowette, S.; Moortgat, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Abdelalim, A. A.; Mohammed, Y.; Salama, E.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ö.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Davignon, O.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Khvedelidze, A.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Savitskyi, M.; Saxena, P.; Shevchenko, R.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Bein, S.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hoffmann, M.; Junkes, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Evangelou, I.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Csanad, M.; Filipovic, N.; Pasztor, G.; Bencze, G.; Hajdu, C.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. 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M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Errico, F.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Guiducci, L.; Marcellini, S.; Masetti, G.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Chatterjee, K.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Sguazzoni, G.; Strom, D.; Viliani, L.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Primavera, F.; Calvelli, V.; Ferro, F.; Robutti, E.; Tosi, S.; Brianza, L.; Brivio, F.; Ciriolo, V.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Malberti, M.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pauwels, K.; Pedrini, D.; Pigazzini, S.; Ragazzi, S.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Esposito, M.; Fabozzi, F.; Fienga, F.; Iorio, A. O. M.; Khan, W. A.; Lanza, G.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; Dall'Osso, M.; De Castro Manzano, P.; Dorigo, T.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Passaseo, M.; Pegoraro, M.; Pozzobon, N.; Ronchese, P.; Rossin, R.; Simonetto, F.; Torassa, E.; Zanetti, M.; Zotto, P.; Braghieri, A.; Fallavollita, F.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Ressegotti, M.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Mantovani, G.; Mariani, V.; Menichelli, M.; Saha, A.; Santocchia, A.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Borrello, L.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, J.; Lee, S.; Lee, S. W.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Moon, D. H.; Oh, G.; Brochero Cifuentes, J. A.; Goh, J.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Kim, J. S.; Lee, H.; Lee, K.; Nam, K.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Ryu, G.; Choi, Y.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Pyskir, A.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Calpas, B.; Di Francesco, A.; Faccioli, P.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. 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H.; Barney, D.; Bianco, M.; Bloch, P.; Bocci, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Di Marco, E.; Dobson, M.; Dorney, B.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Glege, F.; Gulhan, D.; Gundacker, S.; Guthoff, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Karacheban, O.; Kieseler, J.; Kirschenmann, H.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Veres, G. I.; Verweij, M.; Wardle, N.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Bachmair, F.; Bäni, L.; Berger, P.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Klijnsma, T.; Lustermann, W.; Mangano, B.; Marionneau, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Rossini, M.; Schönenberger, M.; Shchutska, L.; Starodumov, A.; Tavolaro, V. R.; Theofilatos, K.; Vesterbacka Olsson, M. L.; Wallny, R.; Zagozdzinska, A.; Zhu, D. H.; Aarrestad, T. K.; Amsler, C.; Caminada, L.; Canelli, M. F.; De Cosa, A.; Donato, S.; Galloni, C.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Seitz, C.; Zucchetta, A.; Candelise, V.; Doan, T. H.; Jain, Sh.; Khurana, R.; Konyushikhin, M.; Kuo, C. M.; Lin, W.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chao, Y.; Chen, K. F.; Chen, P. H.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Miñano Moya, M.; Paganis, E.; Psallidas, A.; Tsai, J. f.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Adiguzel, A.; Boran, F.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Topakli, H.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Karapinar, G.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Tekten, S.; Yetkin, E. A.; Agaras, M. N.; Atay, S.; Cakir, A.; Cankocak, K.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Baber, M.; Bainbridge, R.; Breeze, S.; Buchmuller, O.; Bundock, A.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Di Maria, R.; Dunne, P.; Elwood, A.; Futyan, D.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Matsushita, T.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Shtipliyski, A.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Winterbottom, D.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. 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P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Perry, T.; Prosper, H.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Royon, C.; Sanders, S.; Schmitz, E.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Benaglia, A.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Svyatkovskiy, A.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

2018-04-01

Normalized differential cross sections for top quark pair production are measured in the dilepton (e+e-, μ + μ -, and μ ∓e±) decay channels in proton-proton collisions at a center-of-mass energy of 13 TeV. The measurements are performed with data corresponding to an integrated luminosity of 2.1 fb-1 using the CMS detector at the LHC. The cross sections are measured differentially as a function of the kinematic properties of the leptons, jets from bottom quark hadronization, top quarks, and top quark pairs at the particle and parton levels. The results are compared to several Monte Carlo generators that implement calculations up to next-to-leading order in perturbative quantum chromodynamics interfaced with parton showering, and also to fixed-order theoretical calculations of top quark pair production up to next-to-next-to-leading order. [Figure not available: see fulltext.

Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

PubMed Central

Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

2015-01-01

We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

Importance of maternal diabetes on the chronological deregulation of the intrauterine development: an experimental study in rat.

PubMed

Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

2015-01-01

We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells.

A Pilot Study of Quantitative MRI Measurements of Ventricular Volume and Cortical Atrophy for the Differential Diagnosis of Normal Pressure Hydrocephalus

PubMed Central

Moore, Dana W.; Kovanlikaya, Ilhami; Heier, Linda A.; Raj, Ashish; Huang, Chaorui; Chu, King-Wai; Relkin, Norman R.

2012-01-01

Current radiologic diagnosis of normal pressure hydrocephalus (NPH) requires a subjective judgment of whether lateral ventricular enlargement is disproportionate to cerebral atrophy based on visual inspection of brain images. We investigated whether quantitative measurements of lateral ventricular volume and total cortical thickness (a correlate of cerebral atrophy) could be used to more objectively distinguish NPH from normal controls (NC), Alzheimer's (AD), and Parkinson's disease (PD). Volumetric MRIs were obtained prospectively from patients with NPH (n = 5), PD (n = 5), and NC (5). Additional NC (n = 5) and AD patients (n = 10) from the ADNI cohort were examined. Although mean ventricular volume was significantly greater in the NPH group than all others, the range of values overlapped those of the AD group. Individuals with NPH could be better distinguished when ventricular volume and total cortical thickness were considered in combination. This pilot study suggests that volumetric MRI measurements hold promise for improving NPH differential diagnosis. PMID:21860791

Repeated maternal intramuscular or intraamniotic erythromycin incompletely resolves intrauterine Ureaplasma parvum infection in a sheep model of pregnancy.

PubMed

Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Watts, Rory; Megharaj, Smruthi; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Spiller, O Brad; Keelan, Jeffrey A; Newnham, John P

2014-08-01

Ureaplasma spp are the most commonly isolated microorganisms in association with preterm birth. Maternal erythromycin administration is a standard treatment for preterm prelabor rupture of membranes. There is little evidence of its effectiveness in eradicating Ureaplasma spp from the intrauterine cavity and fetus. We used a sheep model of intrauterine Ureaplasma spp infection to investigate the efficacy of repeated maternal intramuscular and intraamniotic erythromycin treatment to eradicate such an infection. Thirty ewes with singleton pregnancies received an intraamniotic injection of 10(7) color change units of erythromycin-sensitive Ureaplasma parvum serovar 3 at 55 days' gestation. At 116 days' gestation, 28 ewes with viable fetuses were randomized to receive (1) intraamniotic and maternal intramuscular saline solution treatment (n = 8), (2) single intraamniotic and repeated maternal intramuscular erythromycin treatment (n = 10), or (3) single maternal intramuscular and repeated intraamniotic erythromycin treatment (n = 10). Fetuses were surgically delivered at 125 days' gestation. Treatment efficacy was assessed by culture, quantitative polymerase chain reaction, and histopathologic evaluation. Animals treated with intraamniotic erythromycin had significantly less viable U parvum serovar 3 in the amniotic fluid at delivery. However, neither combination of maternal intramuscular and intraamniotic erythromycin treatment successfully cleared U parvum serovar 3 from the amniotic fluid or fetal tissues. Three de novo erythromycin-resistant U parvum isolates were identified in erythromycin-treated animals. Erythromycin treatment, given both to the ewe and into the amniotic cavity, fails to eradicate intrauterine and fetal U parvum serovar 3 infection and may lead to development of erythromycin resistant U parvum. Copyright © 2014 Mosby, Inc. All rights reserved.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

PubMed

Alcántara-Alonso, Viridiana; Alvarez-Salas, Elena; Matamoros-Trejo, Gilberto; de Gortari, Patricia

2017-10-18

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Level of Intrauterine Cocaine Exposure and Neuropsychological Test Scores in Preadolescence: Subtle Effects on Auditory Attention and Narrative Memory

PubMed Central

Beeghly, Marjorie; Rose-Jacobs, Ruth; Martin, Brett M.; Cabral, Howard J.; Heeren, Timothy C.; Frank, Deborah A.

2014-01-01

Neuropsychological processes such as attention and memory contribute to children's higher-level cognitive and language functioning and predict academic achievement. The goal of this analysis was to evaluate whether level of intrauterine cocaine exposure (IUCE) alters multiple aspects of preadolescents' neuropsychological functioning assessed using a single age-referenced instrument, the NEPSY: A Developmental Neuropsychological Assessment (NEPSY) [71], after controlling for relevant covariates. Participants included 137 term 9.5-year-old children from low-income urban backgrounds (51% male, 90% African American/Caribbean) from an ongoing prospective longitudinal study. Level of IUCE was assessed in the newborn period using infant meconium and maternal report. 52% of the children had IUCE (65% with lighter IUCE, and 35% with heavier IUCE), and 48% were unexposed. Infants with Fetal Alcohol Syndrome, HIV seropositivity, or intrauterine exposure to illicit substances other than cocaine and marijuana were excluded. At the 9.5-year follow-up visit, trained examiners masked to IUCE and background variables evaluated children's neuropsychological functioning using the NEPSY. The association between level of IUCE and NEPSY outcomes was evaluated in a series of linear regressions controlling for intrauterine exposure to other substances and relevant child, caregiver, and demographic variables. Results indicated that level of IUCE was associated with lower scores on the Auditory Attention and Narrative Memory tasks, both of which require auditory information processing and sustained attention for successful performance. However, results did not follow the expected ordinal, dose-dependent pattern. Children's neuropsychological test scores were also altered by a variety of other biological and psychosocial factors. PMID:24978115

Mother's prior intrauterine position affects the sex ratio of her offspring in house mice.

PubMed

Vandenbergh, J G; Huggett, C L

1994-11-08

Sex ratio alterations related to environmental factors occur in several mammals, but no mechanism has been identified to explain the adjustment. Intrauterine position (IUP) may provide the context in which such alterations occur. Previous studies on house mice and gerbils reveal that the position of a fetus in the uterus in relation to the sex of its neighbors influences its later anatomy, physiology, and behavior. The anogenital distance (AGD) of females located between two males (2M) is longer than that of females not between two males (OM). We have found that the IUP, as determined by cesarean section and by an index of the AGD, correlates with the sex ratio of the litters produced by female mice. The sex ratio of the first litter born to 2M females was 58% males, for 1M females was 51% males and for OM females was 42% males. The effect on sex ratio continues into the second litter. The number of pups produced by mothers of different IUPs in her first two litters did not differ, suggesting that the sex ratio adjustment occurs prior to parturition. These results provide a basis for the natural variability observed in sex ratios of litter-bearing mammals and suggest that one or more intrauterine mechanisms may be responsible for environmentally related sex ratio alterations.

Two familial cases with a lethal gracile bone dysplasia and intrauterine growth retardation.

PubMed

Korniszewski, Lech; Arbuckle, Susan; Kozlowski, Kazimierz

2003-05-01

A number of more or less distinct entities with low birth weight and abnormal radiographic appearances have been identified. We studied two sisters who were unusual because of severe intrauterine growth restriction, absence of growth after birth, decrease of pre- and postnatal spontaneous mobility, and early fatal outcome. The chondro-osseous morphology documented a distinctive osteochondrodysplasia. The radiographic examination was superficially similar to gracile bone dysplasias but was inconsistent with any known types of this group. These two patients appear to have a unique gracile bone dysplasia. Copyright 2003 Wiley-Liss, Inc.

Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial.

PubMed

Madden, Tessa; Proehl, Sarah; Allsworth, Jenifer E; Secura, Gina M; Peipert, Jeffrey F

2012-02-01

The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. Copyright © 2012 Mosby, Inc. All rights reserved.

Differences in cortical development assessed by fetal MRI in late-onset intrauterine growth restriction.

PubMed

Egaña-Ugrinovic, Gabriela; Sanz-Cortes, Magdalena; Figueras, Francesc; Bargalló, Nuria; Gratacós, Eduard

2013-08-01

The objective of the study was to evaluate cortical development parameters by magnetic resonance imaging (MRI) in late-onset intrauterine growth-restricted (IUGR) fetuses and normally grown fetuses. A total of 52 IUGR and 50 control fetuses were imaged using a 3T MRI scanner at 37 weeks of gestational age. T2 half-Fourier acquisition single-shot turbo spin-echo anatomical acquisitions were obtained in 3 planes. Cortical sulcation (fissures depth corrected by biparietal diameter), brain volumetry, and asymmetry indices were assessed by means of manual delineation and compared between cases and controls. Late-onset IUGR fetuses had significantly deeper measurements in the left insula (late-onset IUGR: 0.293 vs control: 0.267; P = .02) and right insula (0.379 vs 0.318; P < .01) and the left cingulate fissure (0.096 vs 0.087; P = .03) and significantly lower intracranial (441.25 cm(3) vs 515.82 cm(3); P < .01), brain (276.47 cm(3) vs 312.07 cm(3); P < .01), and left opercular volumes (2.52 cm(3) vs 3.02 cm(3); P < .01). IUGR fetuses showed significantly higher right insular asymmetry indices. Late-onset IUGR fetuses had a different pattern of cortical development assessed by MRI, supporting the existence of in utero brain reorganization. Cortical development could be useful to define fetal brain imaging-phenotypes characteristic of IUGR. Copyright © 2013 Mosby, Inc. All rights reserved.

Clinical characteristic and intraoperative findings of uterine perforation patients in using of intrauterine devices (IUDs).

PubMed

Sun, Xin; Xue, Min; Deng, Xinliang; Lin, Yun; Tan, Ying; Wei, Xueli

2018-01-01

Intrauterine devices (IUDs) are the most popular form of contraception used worldwide; however, IUD is not risk-free. IUD migrations, especially uterine perforations, were frequently occurred in patients. The aim of this study was to investigate the clinical characteristics and intraoperative findings in patients with migrated IUDs. 29 cases of uterine perforation associated with migrated IUDs and 69 control patients were followed between January 2008 to March 2015. Patients who used IUDs within first 6 months from the last delivery experienced a characteristically high rate of the perforation of the uterine wall. A significantly larger number of IUD insertion associated with uterine perforation were performed in rural hospitals or operated at a lower level health care system. There was no clear difference in the age and presented symptoms in patients between two groups. Majority of contraceptive intrauterine devices was the copper-releasing IUDs. Furthermore, patients who used V-shaped IUD showed significantly higher incidence of pelvic adhesions when compared with the users of O-shaped IUDs. Unique clinical characteristics of IUD migration were identified in patients with uterine perforation. Hysteroscopy and/or laparoscopy were the effective approaches to remove the migrated IUDs. Improving operating skills is required at the lower level of health care system.

The effect of intrauterine position on the survival, reproduction and home range size of female house mice (Mus musculus)

Treesearch

W. J. Zielinski; F. S. vom Saal; J. G. Vandenbergh

1992-01-01

In laboratory studies using albino house mice, a female's prior intrauterine position can affect many postnatal physiological, morphological and behavioral characteristics. Females flanked by males in utero (2M females) exhibit more aggressive dominance than females flanked by females (OM females). Thus, wild 2M...

Not Quite Normal: Consequences of Violating the Assumption of Normality in Regression Mixture Models

ERIC Educational Resources Information Center

Van Horn, M. Lee; Smith, Jessalyn; Fagan, Abigail A.; Jaki, Thomas; Feaster, Daniel J.; Masyn, Katherine; Hawkins, J. David; Howe, George

2012-01-01

Regression mixture models, which have only recently begun to be used in applied research, are a new approach for finding differential effects. This approach comes at the cost of the assumption that error terms are normally distributed within classes. This study uses Monte Carlo simulations to explore the effects of relatively minor violations of…

Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders.

PubMed

Bao, Ai-Min; Swaab, Dick F

2011-04-01

During the intrauterine period a testosterone surge masculinizes the fetal brain, whereas the absence of such a surge results in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other. Sex differences in cognition, gender identity (an individual's perception of their own sexual identity), sexual orientation (heterosexuality, homosexuality or bisexuality), and the risks of developing neuropsychiatric disorders are programmed into our brain during early development. There is no evidence that one's postnatal social environment plays a crucial role in gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with any changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other. Copyright © 2011 Elsevier Inc. All rights reserved.

Fertility control using intrauterine devices: an alternative for population control in wild horses.

PubMed

Daels, P F; Hughes, J P

1995-10-01

The purpose of this study was to develop a contraceptive method for feral horses. The feral horse population has increased significantly in recent years despite attempts to control numbers. As in most wild animal population control programs, contraceptive methods must be easy to apply, cause minimal disruption to the social structure and be fully reversible. In the present study, we tested the effectiveness of an intrauterine device (IUD) for fertility control in mares. Six mares were fitted with a silastic O-ring-shaped IUD on July 1 of Year 1. The IUD-treated mares were turned out with 12 nontreated mares and a fertile stallion in a large pasture until October 20 (112 d). None of the IUD-treated mares and all the nontreated mares became pregnant. The IUD-treated mares were maintained separately from the stallion during the winter. Following removal of the IUD on April 27 of Year 2, the mares were again introduced to the pasture with the stallion together with 6 nontreated mares. For the 6 mares previously treated with an IUD, the mean interval from introduction to the stallion to conception was 17.5 +/- 5 d or 1.3 cycles per pregnancy, and all mares produced a normal foal at term. Subsequently, 19 recorded mare breeding seasons resulted in 18 foals. Uterine cytology and histopathology indicate that the IUD causes mild chronic endometritis without permanent changes in the endometrium. We conclude that based on our observations, the O-ring-shaped IUD is an effective, safe and practical contraceptive method for mares.

Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth: Effects on Nephron Number and Long-Term Renal Health

PubMed Central

Zohdi, Vladislava; Sutherland, Megan R.; Lim, Kyungjoon; Gubhaju, Lina; Zimanyi, Monika A.; Black, M. Jane

2012-01-01

Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension. PMID:22970368

Modulation of body fluids and angiotensin II receptors in a rat model of intra-uterine growth restriction.

PubMed

Bédard, Sophie; Sicotte, Benoit; St-Louis, Jean; Brochu, Michèle

2005-02-01

We previously reported that sodium restriction during pregnancy reduces plasma volume expansion and promotes intra-uterine growth restriction (IUGR) in rats while it activates the renin-angiotensin-aldosterone system (RAAS). In the present study, we proceeded to determine whether expression of the two angiotensin II (ANGII) receptor subtypes (AT(1) and AT(2)) change in relation to maternal water-electrolyte homeostasis and fetal growth. To this end, pregnant (gestation day 15) and non-pregnant Sprague-Dawley rats were randomly assigned to two groups fed either normal, or Na(+)-restricted diets for 7 days. At the end of the treatment period, plasma aldosterone and renin activity as well as plasma and urine electrolytes were measured. Determinations for AT(1) and AT(2) mRNA and protein were made by RNase protection assay and photoaffinity labelling, respectively, using a number of tissues implicated in volume regulation and fetal growth. In non-pregnant rats, Na(+) restriction decreases Na(+) excretion without altering plasma volume, plasma Na(+) concentration or the expression of AT(1) and AT(2) mRNA or protein in the tissues examined. In normally fed pregnant rats when compared to non-pregnant controls, AT(1) mRNA increases in the hypothalamus as well as pituitary and declines in uterine arteries, while AT(1) protein decreases in the kidney and AT(2) mRNA declines in the adrenal cortex. In pregnant rats, Na(+) restriction induces a decrease in plasma Na(+), an increase in plasma urea, as well as a decline in renal urea and creatinine clearance rates. Protein levels for both AT(1) and AT(2) in the pituitary and AT(2) mRNA in the adrenal cortex are lower in the Na(+)-restricted pregnant group when compared to normally fed pregnant animals. Na(+) restriction also induces a decrease in AT(1) protein in the placenta. In conclusion, these results suggest that pregnancy may increase sensitivity to Na(+) depletion by the tissue-specific modulation of ANGII receptors

Assessment of menstrual blood loss in Belgian users of a new T-shaped levonorgestrel-releasing intrauterine system.

PubMed

Wildemeersch, Dirk; Rowe, Patrick J

2005-06-01

This study was conducted to evaluate the effect of a T-shaped levonorgestrel-releasing intrauterine system (Femilis, LNG IUS) on the amount of menstrual blood loss (MBL) in women with and without menorrhagia. The daily release of the LNG IUS was approximately 20 mug. In 60 Belgian women, less than 48 years of age at study enrollment, using the Femilis LNG IUS for 4 to more than 30 months, MBL was assessed with the visual assessment technique. Twenty-eight women had normal menstrual periods at baseline (menstrual score <185) and 32 women had idiopathic menorrhagia (menstrual score > or =185). Menstrual blood loss scores dropped significantly during the observation period in all women except one. The median menstrual score at baseline in women with normal menstrual bleeding was 140 (range 80-160) and dropped to a median score of 5 (range 0-150) at follow-up, a decrease of 96%. In the 32 women with menorrhagic bleeding at baseline, menstrual flow dropped from a median score of 232 (range 185-450) at baseline to a median score of 3 (range 0-50) at follow-up, a decrease of 99%. Twenty women developed amenorrhea (33%): 10 in the group of women with normal menstruation and 10 in those women with menorrhagia. Most of the remaining women had oligomenorrhea requiring the use of a few panty-liners only. In one woman, MBL did not decrease, thus requiring further evaluation. The impact on MBL of this new 20 mug/day LNG-releasing IUS confirms other studies with devices releasing the same or lower amounts of LNG. The strong endometrial suppression is the principal mechanism explaining the effect on MBL. The strong effect on MBL of this contraceptive method offers an important health benefit and improvement in quality of life, particularly in women with heavy bleeding and anemia, as other treatment modalities are less effective, more costly, more invasive or not readily available.

Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas

PubMed Central

Zhang, Lin; Chen, Wei; Dai, Yuee

2016-01-01

Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. PMID:27190278

Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler

PubMed Central

Mazarico, E.; Martinez-Cumplido, R.; Díaz, M.; Sebastiani, G.; Ibáñez, L.; Gómez-Roig, M. D.

2016-01-01

Introduction Infant anthropometry and body composition have been previously assessed to gauge the impact of intrauterine growth restriction (IUGR) at birth, but the interplay between prenatal Doppler measurements and postnatal development has not been studied in this setting. The present investigation was performed to assess the significance of prenatal Doppler findings relative to postnatal anthropometrics and body composition in IUGR newborns over the first 12 months of life. Patients and Methods Consecutive cases of singleton pregnancies with suspected IUGR were prospectively enrolled over 12 months. Fetal biometry and prenatal Doppler ultrasound examinations were performed. Body composition was assessed by absorptiometry at ages 10 days, and at 4 and12 months. Results A total of 48 pregnancies qualifying as IUGR were studied. Doppler parameters were normal in 26 pregnancies. The remaining 22 deviated from normal, marked by an Umbilical Artery Pulsatility Index (UA-PI) >95th centil or Cerebro-placental ratio (CPR) <5th centile. No significant differences emerged when comparing anthropometry and body composition at each time point, in relation to Doppler findings. Specifically, those IUGR newborns with and without abnormal Doppler findings had similar weight, length, body mass index, lean and fat mass, and bone mineral content throughout the first 12 months of life. In a separate analysis, when comparing IUGR newborns by Doppler (abnormal UA-PI vs. abnormal CPR), anthropometry and body composition did not differ significantly. Conclusions Infants with IUGR maintain a pattern of body composition during the first year of life that is independent of prenatal Doppler findings. Future studies with larger sample sizes and correlating with hormonal status are warranted to further extend the phenotypic characterization of the various conditions now classified under the common label of IUGR. PMID:26938993

Symptoms of an Intrauterine Hematoma Associated with Pregnancy Complications: A Systematic Review

PubMed Central

Xiang, Lan; Wei, Zhaolian; Cao, Yunxia

2014-01-01

Objective To evaluate the predictive value of the symptoms of an intrauterine hematoma (IUH) for adverse pregnancy outcomes. Methods A literature review was performed with the search terms, including intrauterine/subchorionic/retroplacental/subplacental hematoma/hemorrhage/bleeding/collection/fluid, covering the period from January, 1981 to January, 2014. We just focused on the pregnancy outcomes associated with different symptoms of an IUH. Results It is generally agreed that a retroplacental, posterior or subchorionic in the fundus of uterus, and/or persistent IUH is associated with adverse outcomes in the ongoing pregnancy. However, the prognosis value of both volume and gestational age at diagnosis of IUH still remains controversial. Some researchers argue that a large IUH is associated with an increased risk of adverse events during pregnancy while others refuted. It is believed by some that the earlier an IUH was detected, the higher the risk for adverse outcomes would be, while no or weak association were reported by other studies. The prognostic value of the simultaneous presence of vaginal bleeding on pregnancy outcome is also controversial. Conclusions Both the position relative to the placenta or uterus and duration of IUH have strong predictive value on the prognosis in the ongoing pregnancy. However, the prognostic values of the IUH volume, gestational age at diagnosis and the simultaneous presence of vaginal bleeding remain controversial up to now. Moreover, most of previous reports are small, uncontrolled studies with incomplete information. Prospective, large sample, cohorts studies which take all detailed symptoms of an IUH into consideration are needed when we evaluate its clinical significance in the prognosis of pregnancy. PMID:25369062

The effect of prolonged intrauterine hyperinsulinemia on iron utilization in fetal sheep.

PubMed

Georgieff, M K; Widness, J A; Mills, M M; Stonestreet, B S

1989-11-01

Newborn infants of poorly controlled insulin-dependent diabetic mothers demonstrate a redistribution of iron from serum and tissue stores into red blood cells. These changes may be due to increases in iron utilization during augmented Hb synthesis, which compensates for chronic intrauterine hypoxemia induced by prolonged fetal hyperinsulinemia. We tested this hypothesis by measuring plasma iron, total iron-binding capacity, percent iron-binding capacity saturation (total iron-binding capacity saturation), Hb concentration, total red cell Hb, and total red cell iron in the arterial blood of 11 chronically instrumented fetal sheep after 7-12 d of infusion with 15 U/day of insulin (n = 5) or placebo (n = 6). The insulin-infused fetal sheep had higher mean +/- SD plasma insulin concentrations (448 +/- 507 versus 11 +/- 8 mU/L; p less than 0.001) and lower arterial oxygen saturations (38 +/- 7 versus 54 +/- 9%; p less than 0.02). The insulin-infused group had a lower mean plasma iron concentration (20.8 +/- 10.9 versus 42.1 +/- 14.7 microM/L; p less than 0.02) and total iron-binding capacity saturation (36 +/- 20 versus 64 +/- 22%; p less than 0.02) and a higher total red cell Hb (45.4 +/- 8.7 versus 32.6 +/- 8.8 g; p less than 0.02) and total red cell iron content (154 +/- 29 versus 111 +/- 29 mg; p less than 0.02) when compared with the placebo group. Seven to 12 d of intrauterine hyperinsulinemia decreases serum iron and increases total red cell iron, most likely by stimulating increased Hb synthesis in response to low arterial oxygen saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring

PubMed Central

Dasinger, John Henry; Fahling, Joel M.; Backstrom, Miles A.; Alexander, Barbara T.

2017-01-01

Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis. PMID:29145418

Fertilization and embryo recovery rates in superovulated chios ewes after laparoscopic intrauterine insemination.

PubMed

Lymberopoulos, A G; Amiridis, G S; Kühholzer, B; Besenfelder, U; Christodoulou, V; Vainas, E; Brem, G

2001-06-01

Forty superovulated dairy ewes of the Greek Chios breed were used in an experiment to evaluate the efficiency of laparoscopic intrauterine insemination on fertilization and embryo recovery rates as well as embryo quality. Estrus was synchronized by intravaginal progestagen impregnated sponges and superovulation was induced by administration of 8.8 mg o-FSH i.m. following a standard 8 dose protocol. A small volume (0.3 mL) of diluted fresh ram semen was deposited in each uterine horn 24 to 28 h after onset of the estrus by a laparoscopic technique. The animals were allocated randomly into two groups (Group A and B) of 20 animals each. In Group A, embryos were recovered 18 to 24 h after the intrauterine insemination and in Group B on Day 6. The average number of corpora lutea was 12.8 +/- 1.2 and 11.5 +/- 1.1 (+/- SEM); the overall embryo recovery was 66.4% and 57% and the percentage of recovered fertilized ova was 81% and 82.8% in Groups A and B, respectively. More fertilized ova were collected per ewe from Group A (P < or = 0.1). Results indicated that in Chios breed, superovulation using homologous FSH combined with laparoscopic AI leads to good ovarian response with satisfactory results in fertilization, embryo recovery and quality of embryos. This could lead to improved and more efficient methods for obtaining large numbers of high quality oocytes and embryos for embryo transfer programs which could contribute to genetic improvement and increase of the population size.

Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

PubMed Central

Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T.; Black, M. Jane

2014-01-01

Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. PMID:25551250

Fuel cell system logic for differentiating between rapid and normal shutdown commands

DOEpatents

Keskula, Donald H.; Doan, Tien M.; Clingerman, Bruce J.

2000-01-01

A method of controlling the operation of a fuel cell system wherein each shutdown command for the system is subjected to decision logic which determines whether the command should be a normal shutdown command or rapid shutdown command. If the logic determines that the shutdown command should be a normal shutdown command, then the system is shutdown in a normal step-by-step process in which the hydrogen stream is consumed within the system. If the logic determines that the shutdown command should be a rapid shutdown command, the hydrogen stream is removed from the system either by dumping to atmosphere or routing to storage.

Level of intrauterine cocaine exposure and neuropsychological test scores in preadolescence: subtle effects on auditory attention and narrative memory.

PubMed

Beeghly, Marjorie; Rose-Jacobs, Ruth; Martin, Brett M; Cabral, Howard J; Heeren, Timothy C; Frank, Deborah A

2014-01-01

Neuropsychological processes such as attention and memory contribute to children's higher-level cognitive and language functioning and predict academic achievement. The goal of this analysis was to evaluate whether level of intrauterine cocaine exposure (IUCE) alters multiple aspects of preadolescents' neuropsychological functioning assessed using a single age-referenced instrument, the NEPSY: A Developmental Neuropsychological Assessment (NEPSY) (Korkman et al., 1998), after controlling for relevant covariates. Participants included 137 term 9.5-year-old children from low-income urban backgrounds (51% male, 90% African American/Caribbean) from an ongoing prospective longitudinal study. Level of IUCE was assessed in the newborn period using infant meconium and maternal report. 52% of the children had IUCE (65% with lighter IUCE, and 35% with heavier IUCE), and 48% were unexposed. Infants with Fetal Alcohol Syndrome, HIV seropositivity, or intrauterine exposure to illicit substances other than cocaine and marijuana were excluded. At the 9.5-year follow-up visit, trained examiners masked to IUCE and background variables evaluated children's neuropsychological functioning using the NEPSY. The association between level of IUCE and NEPSY outcomes was evaluated in a series of linear regressions controlling for intrauterine exposure to other substances and relevant child, caregiver, and demographic variables. Results indicated that level of IUCE was associated with lower scores on the Auditory Attention and Narrative Memory tasks, both of which require auditory information processing and sustained attention for successful performance. However, results did not follow the expected ordinal, dose-dependent pattern. Children's neuropsychological test scores were also altered by a variety of other biological and psychosocial factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Platelet concentrate in bovine reproduction: effects on in vitro embryo production and after intrauterine administration in repeat breeder cows.

PubMed

Lange-Consiglio, Anna; Cazzaniga, Nadia; Garlappi, Rosangela; Spelta, Chiara; Pollera, Claudia; Perrini, Claudia; Cremonesi, Fausto

2015-06-19

A repeat breeder cow (RBC) can be defined as an animal that after 3 or more inseminations cannot get pregnant because of fertilization failure or early embryonic death. If no cause is identified precisely, inadequate uterine receptivity is responsible for implantation failures. Since a large number of identified molecular mediators, such as cytokines, growth factors and lipids have been postulated to be involved in early feto-maternal interaction, in this study a different approach to the treatment of RBC syndrome has been employed using a platelet concentrate (PC) that contains a significant amount of growth factors accumulated in its α-granules. Three explorative studies were performed. Initially, PC was supplemented in the in vitro embryo culture medium to study its effect on embryo-development. After the pilot study, 4 RBCs were treated with intrauterine administration of PC to evaluate proliferative potential of endometrium by immunohistochemical expression of the antigen Ki-67. Lastly, the effect of intrauterine administration of PC at 48 hrs after artificial insemination in RBCs was evaluated. The in vitro results show that 5 % of PC and 5 % of fetal calf serum (FCS) increase the rate of blastocysts compared with the control containing 10 % FCS only (43.04 % vs 35.00 % respectively). The immunohistochemical study shows more proliferating nuclei in the treated uterine horn compared to the control one. After intrauterine insemination in RBCs, the percentage of pregnant cows in the control group was 33.33 % compared to 70 % of the treated animals. We suppose that when embryo descends in uterus could find a more appropriate environment for nesting and subsequent pregnancy.

Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

PubMed

Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

2005-01-01

Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

Cell proliferation and differentiation in chemical leukemogenesis

NASA Technical Reports Server (NTRS)

Irons, R. D.; Stillman, W. S.; Clarkson, T. W. (Principal Investigator)

1993-01-01

In tissues such as bone marrow with normally high rates of cell division, proliferation is tightly coordinated with cell differentiation. Survival, proliferation and differentiation of early hematopoietic progenitor cells depend on the growth factors, interleukin 3 (IL-3) and/or granulocyte-macrophage colony stimulating factor (GM-CSF) and their synergism with other cytokines. We provide evidence that a characteristic shared by a diverse group of compounds with demonstrated leukemogenic potential is the ability to act synergistically with GM-CSF. This results in an increase in recruitment of a resting population of hematopoietic progenitor cells normally unresponsive to the cytokine and a twofold increase in the size of the proliferating cell population normally regarded to be at risk of transformation in leukemogenesis. These findings support the possibility that transient alterations in hematopoietic progenitor cell differentiation may be an important factor in the early stages of development of leukemia secondary to chemical or drug exposure.

A randomized trial of levonorgestrel intrauterine system insertion 6 to 48 h compared to 6 weeks after vaginal delivery; lessons learned.

PubMed

Stuart, Gretchen S; Lesko, Catherine R; Stuebe, Alison M; Bryant, Amy G; Levi, Erika E; Danvers, Antoinette I

2015-04-01

The objective of this randomized trial was to compare breastfeeding among women who received a levonorgestrel-releasing intrauterine system within 6-48 h (early) or 4-6 weeks (standard) after an uncomplicated vaginal birth. Analysis groups of 86 women in each arm were needed to demonstrate a 20% difference in any breastfeeding. Thirty-five women were randomized to the early (N=17) and standard (N=18) arms. The combination of unsuccessful placement (2/17; 12%), expulsions (7/17; 41%) and removals (3/17; 18%) reached 71% (12/17) in the early arm, so the study was stopped. In our small study cohort, levonorgestrel-releasing intrauterine system insertion between 6 and 48 h after vaginal birth was associated with a high rate of expulsion or removal soon after insertion. Copyright © 2015 Elsevier Inc. All rights reserved.

Antenatal glucocorticoid treatment of the growth-restricted fetus: benefit or cost?

PubMed

Morrison, Janna L; Orgeig, Sandra

2009-06-01

Women at risk of preterm labor are commonly treated with antenatal glucocorticoids to reduce neonatal complications, including respiratory distress syndrome. Despite the benefits of antenatal glucocorticoid for neonatal lung function, they are associated with negative cardiovascular outcomes. Among this population, there is a group of intrauterine growth-restricted fetuses in which substrate supply is reduced and these fetuses must undergo a range of cardiovascular adaptations to survive. Interestingly, the cardiovascular changes caused by antenatal glucocorticoid in normally grown fetuses are contrary to the cardiovascular adaptations that the intrauterine growth-restricted fetus must make to survive. Hence, the possibility exists that antenatal glucocorticoid in intrauterine growth-restricted infants may compromise cardiovascular development. This review first provides an overview of general antenatal glucocorticoid effects, before outlining the effects on cardiorespiratory development in normally grown fetuses, the cardiovascular adaptations that occur in the intrauterine growth-restricted fetus and finally integrating this with the very limited evidence for the effect of antenatal glucocorticoid in intrauterine growth-restricted infants.