RESUMO
Objective: We aimed to identify in this study time trends of relapses in the illicit consumption of narcotics in a special at-risk population of former drug users under a public health perspective. Methods: In a pooled dataset of 14 consecutive calendar years (2006-2019), the use of seven different narcotic substances was studied in 380 persons with a total of 2,928 urine samples which were analyzed using a valid marker system for narcotic residues. Results: During the entire observation period, the relapse rate for cannabinoids and opiates was the highest despite abstinence requirements. It was noticeable that the relapses across all narcotics groups occurred primarily during the first 3 years of the probation period (90%) with a decrease in illegal consumption during the following years of the observation period. Conclusion: Special attention should be paid to probationers at the beginning of the probation period to develop more effective prevention strategies for substance abstinence by all involved actors in public health services.
Assuntos
Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Fatores de Risco , Entorpecentes , Serviços de SaúdeRESUMO
INTRODUCTION: Trophoblast homing to maternal spiral arteries is mandatory for successful placentation. Cell-cell adhesion molecules regulate this process and adhesion molecule expression is altered in impaired placentation. We hypothesize that, similar to immune cell recruitment, trophoblast cell adherence and rolling are primarily mediated by adhesion molecules like, cadherins, immunoglobulins, selectins and their partnering ligands. Here, the interdependence of adhesion molecule expression in trophoblastic cell lines of diverse origin was investigated in relation to their interaction with endothelial cell networks on Matrigel® co-cultures and the effect of specific adhesion molecule knockdown analyzed. METHODS: Trophoblastic cells were labeled in red and co-cultured with green HUVEC networks on Matrigel®. Association was quantified after collection of fluorescence microscopy pictures using Wimasis® internet platform and software. Expression of adhesion molecules was analyzed by PCR and Western blot, immuno-fluorescence and flow cytometry. The impact of adhesion molecules on trophoblast-endothelial-cell interaction was investigated using siRNA technique. RESULTS: N-cadherin and CD162 were specifically expressed in the trophoblast cell line HTR-8/SVneo, which closely adhere to and actively migrate toward HUVEC networks on Matrigel®. Suppression of N-cadherin led to a significant alteration in trophoblast-endothelial cell interaction. Expression of VE-cadherin in closely interacting trophoblast cells was not confirmed in vitro. DISCUSSION: We identified N-cadherin to mediate specific interaction between HUVEC and the migrating trophoblast cells HTR-8/SVneo in a Matrigel® co-culture model. VE-cadherin contribution could not be confirmed in vitro. Our results support the hypothesis that impaired N-cadherin but not VE-cadherin expression is involved in trophoblast recruitment to the maternal endothelium.
Assuntos
Caderinas/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Endoteliais/metabolismo , Endotélio/metabolismo , Trofoblastos/citologia , Comunicação Celular/fisiologia , Técnicas de Cultura de Células , Movimento Celular/fisiologia , Feminino , Humanos , Placentação/fisiologia , GravidezRESUMO
The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis.
Assuntos
Biomarcadores/metabolismo , Células Endoteliais/citologia , Feto/irrigação sanguínea , Macrófagos/citologia , Placenta/irrigação sanguínea , Adulto , Células Cultivadas , Citocinas/metabolismo , Feminino , Feto/citologia , Feto/fisiologia , Humanos , Masculino , Neovascularização Fisiológica , Fenótipo , Placenta/citologia , Placenta/fisiologia , GravidezRESUMO
STUDY QUESTION: How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy? SUMMARY ANSWER: Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space. WHAT IS KNOWN ALREADY: Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells. STUDY DESIGN, SIZE, DURATION: As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis. PARTICIPANTS/MATERIALS, SETTING, METHODS: First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5-11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations. WIDER IMPLICATIONS OF THE FINDINGS: This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now.
Assuntos
Decídua/citologia , Placenta/citologia , Placentação/fisiologia , Trofoblastos/citologia , Técnicas de Cocultura , Feminino , Humanos , Gravidez , Primeiro Trimestre da GravidezRESUMO
Trophoblast invasion into uterine tissues represents a hallmark of first trimester placental development. As expression of serum amyloid A4 (SAA4) occurs in tumorigenic and invasive tissues we here investigated whether SAA4 is present in trophoblast-like human AC1-M59/Jeg-3 cells and trophoblast preparations of human first trimester and term placenta. SAA4 mRNA was expressed in non-stimulated and cytokine-treated AC1-M59/Jeg-3 cells. In purified trophoblast cells SAA4 mRNA expression was upregulated at weeks 10 and 12 of pregnancy. Western-blot and immunohistochemical staining of first trimester placental tissue revealed pronounced SAA4 expression in invasive trophoblast cells indicating a potential role of SAA4 during invasion.
Assuntos
Proteína Amiloide A Sérica/metabolismo , Trofoblastos/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da GravidezRESUMO
Cell transplantation is a promising strategy in regenerative medicine for revascularization of ischemic tissues. Based on our observation that placental mesenchymal stromal cells (PMSC) enhance endothelial cell viability in vitro via secretion of angiogenic factors, we asked whether PMSC support vascular growth in vivo. PMSC were isolated from amnion and placental endothelial cells (PLEC) from chorion and either separately or co-transplanted subcutaneously into immune-deficient mice. Co-transplantation resulted in a higher number of perfused human vessels (CD31+/vimentin+) containing mouse glycophorin A+ erythrocytes. Results indicate positive effects of PMSC on neovascularization in vivo, making them attractive candidates to create autologous PMSC/PLEC pairs for research and transplantation.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica , Placenta/citologia , Animais , Células Endoteliais/fisiologia , Células Endoteliais/transplante , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Modelos Animais , Placenta/irrigação sanguínea , Gravidez , Medicina RegenerativaRESUMO
STUDY QUESTION: Do decidual natural killer (dNK) cells and decidual macrophages (dMph) become enriched in the vicinity of the trophoblast invasion front? SUMMARY ANSWER: Morphometric image analysis and areal cell density calculations, which excluded observer bias, showed an enrichment of decidual leukocytes in the neighbourhood of the trophoblast invasion front. WHAT IS KNOWN ALREADY: In previous studies, the number of decidual leukocytes was visually counted in medium- or high power fields. These methods, however, cannot reveal the exact spatial relationship between leukocytes and invasive trophoblast cells, and are therefore prone to subjective errors. Thus, a more objective approach is required. STUDY DESIGN, SIZE, DURATION: Applying a new method of morphometric image analysis, leukocyte populations were studied in human tissue fragments derived from first trimester placentation sites (n = 7) as well as in co-cultures of first trimester decidual tissue with placental villi of the same pregnancy representing an appropriate in vitro model of trophoblast invasion (n = 15). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: First trimester decidual tissue was obtained from women undergoing elective terminations of pregnancy at 7-10 weeks of gestational age. Tissue sections were double-stained immunohistochemically for markers of dNK cells or dMph on one hand, and for invasive extravillous trophoblast cells on the other. To analyse the distribution of leukocytes, distinct cell compartments as well as cell neighbourhood areas were defined. Finally, relative areal cell densities were calculated and these data were compared with those of an in vitro model of trophoblast invasion as well as with tissue fragments derived from decidua parietalis without trophoblast cells. MAIN RESULTS AND THE ROLE OF CHANCE: At first trimester placentation sites, a higher density of dNK cells as well as of dMph was found in close proximity to the invasive trophoblast (P ≤ 0.01), compared with the average areal cell density of decidual leukocytes in the tissue with exclusion of the trophoblast. The highest areal cell density of leukocytes was determined up to a distance of 20 µm from the trophoblast cells, whereas in more distant regions it was even lower than average, indicating a migration of these leukocytes towards the trophoblast invasion front. In the three-dimensional co-culture model, however, we found an enrichment of dMph (P ≤ 0.01) but not of dNK cells (P > 0,05) in the neighbourhood of the invasive trophoblast. LIMITATIONS, REASONS FOR CAUTION: The morphometric image analysis depends on intense immunohistochemical staining that is free of background and cross-reactivity. WIDER IMPLICATIONS OF THE FINDINGS: The presented method will be useful not only for the investigation of recurrent miscarriage but also in the fields of tumour immunology and inflammation. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the European Commission (Network of Excellence 'The Control of Embryo Implantation (EMBIC)', FP6-512040, lead researcher: P.S.), and by the Franz Lanyar Foundation of the Medical University of Graz, Austria (Grant #347). None of the authors declared a conflict of interests.
Assuntos
Decídua/citologia , Células Matadoras Naturais/citologia , Macrófagos/citologia , Trofoblastos/fisiologia , Contagem de Células , Movimento Celular , Técnicas de Cocultura , Feminino , Humanos , Células Matadoras Naturais/fisiologia , Leucócitos/citologia , Gravidez , Primeiro Trimestre da Gravidez , Trofoblastos/citologiaRESUMO
BACKGROUND: Red blood cells (RBCs) are routinely stored in liquid state at temperatures below 6°C, and RBC unit core temperature should not exceed 10°C during transport. Since the critical temperature of 10°C was chosen mostly arbitrarily, this study investigated the effect of both constant temperature settings as well as multiple rewarming cycles on stored RBCs with respect to morphology, biochemical parameters and haemolysis. MATERIALS AND METHODS: Buffy coat-depleted filtered RBCs were used as standard products. RBCs were stored at 1-6°C (reference group, n = 12), 13 and 22°C (test groups, n = 12 each) or stored at 1-6°C and warmed up five times to 10, 13, or 22°C for a period of 24 h each. Various biochemical parameters were measured weekly. RBCs were further investigated using electron microscopy. RESULTS: Red blood cells stored constantly at 13 or 22°C showed stable haemolysis rates until day 28 and day 14, respectively. RBCs stored at 1-6°C with five warming-up periods to 10, 13 or 22°C each lasting 24 h (total 120 h) did not exceed the limit of the haemolysis rate at the end of storage. Differently shaped erythrocytes were found in all samples, but more crenate erythrocytes appeared after 42 days of storage independent of temperature profiles. CONCLUSION: Red cells can be kept at constant temperatures above 6°C without apparent harmful effects at least until day 14, whereas multiple warming cycles for no longer than 24 h at 10, 13 or 22°C with subsequent cooling do not cause quality loss as assessed using the in vitro assays employed in this study.
Assuntos
Preservação de Sangue/métodos , Eritrócitos/citologia , Eritrócitos/metabolismo , Hemólise , Temperatura Alta , Humanos , Fatores de TempoRESUMO
Offspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placental function. High plasma levels of particular nutrients in obese and diabetic mothers are likely to be the important drivers of nutrient transfer to the fetus, resulting in excess fat accretion. However, not all offspring of obese and diabetic mothers are born large for gestational age and the explanation may involve the regulation of placental nutrient transfer required for fetal growth. The placenta integrates maternal and fetal signals across gestation in order to determine nutrient transfer rate. Understanding the nature of these signals and placental responses to them is key to understanding the pathology of both fetal growth restriction and macrosomia. The overall effects of the maternal environment on the placenta are the product of its exposures throughout gestation, the 'placental exposome'. Understanding these environmental influences is important as exposures early in gestation, for instance causing changes in the function of genes involved in nutrient transfer, may determine how the placenta will respond to exposures later in gestation, such as to raised maternal plasma glucose or lipid concentrations. Longitudinal studies are required which allow investigation of the influences on the placenta across gestation. These studies need to make full use of developing technologies characterising placental function, fetal growth and body composition. Understanding these processes will assist in the development of preventive strategies and treatments to optimise prenatal growth in those pregnancies at risk of either excess or insufficient nutrient supply and could also reduce the risk of chronic disease in later life.
Assuntos
Adiposidade , Composição Corporal/fisiologia , Feto/metabolismo , Placentação , Peso ao Nascer , Epigênese Genética , Feminino , Desenvolvimento Fetal , Humanos , Troca Materno-Fetal , Obesidade/metabolismo , Gravidez , Resultado da Gravidez , Fatores de RiscoRESUMO
Pregnancy-related complications not only represent a risk for maternal and fetal morbidity and mortality, but are also a risk for several diseases later in life. Many epidemiological studies have shown clear associations between an adverse intrauterine environment and an increased risk of diabetes, hypertension, cardiovascular disease, depression, obesity, and other chronic diseases in the adult. Some of these syndromes could be prevented by avoiding adverse stimuli or insults including psychological stress during pregnancy, intake of drugs, insufficient diet and substandard working conditions. Hence, all of these stimuli have the potential to alter health later in life. The placenta plays a key role in regulating the nutrient supply to the fetus and producing hormones that control the fetal as well as the maternal metabolism. Thus, any factor or stimulus that alters the function of the hormone producing placental trophoblast will provoke critical alterations of placental function and hence could induce programming of the fetus. The factors that change placental development may interfere with nutrient and oxygen supply to the fetus. This may be achieved by a direct disturbance of the placental barrier or more indirectly by, e. g., disturbing trophoblast invasion. For both path-ways, the respective pathologies are known: while preeclampsia is caused by alterations of the villous trophoblast, intra-uterine growth restriction is caused by insufficient invasion of the extravillous trophoblast. In both cases the effect can be undernutrition and/or fetal hypoxia, both of which adversely affect organ development, especially of brain and heart. However, the mechanisms responsible for disturbances of trophoblast differentiation and function remain elusive.
Assuntos
Desenvolvimento Fetal , Doenças Fetais/fisiopatologia , Troca Materno-Fetal , Modelos Biológicos , Placenta/fisiopatologia , Adulto , Feminino , Humanos , Masculino , GravidezAssuntos
Bancos de Espécimes Biológicos/organização & administração , Bancos de Espécimes Biológicos/tendências , Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/tendências , Bases de Dados Genéticas/tendências , Patologia/organização & administração , Patologia/tendências , Adulto , Idoso , Áustria , Bancos de Espécimes Biológicos/ética , Criopreservação , Bases de Dados Genéticas/ética , Ética em Pesquisa , Feminino , Previsões , Hospitais Universitários , Humanos , Consentimento Livre e Esclarecido/ética , Masculino , Pessoa de Meia-Idade , Patologia/ética , Manejo de EspécimesRESUMO
INTRODUCTION: Reduced serum LDL concentrations have been observed in pregnancies complicated by intrauterine growth restriction (IUGR) as compared to healthy pregnant women. Since increased oxidative stress has been suggested to play a major role in IUGR we now hypothesized that the lower LDL concentrations are accompanied by an accumulation of oxidized LDLs in the placenta. METHODS: Fifteen placentas of near term and preterm born IUGR, and a gestational age matched control group (CTRL n = 15) were analyzed. Placental minimal modified LDL and fully oxidized LDL particles were measured by ELISA, and by immunohistochemistry, and were related to maternal and fetal serum lipid profiles. RESULTS: We found fully oxidized LDL but not minimal modified LDL being increased in the preterm subgroup of IUGR (n = 10) as compared to preterm CTRL (n = 10; p < 0.05). An increased staining intensity of trophoblasts in preterm IUGR subjects as compared to preterm CTRL has been confirmed by immunohistochemistry (p < 0.05). No difference could be found between the term groups (n = 5 each). Correlation analysis revealed an inverse relationship of maternal LDL (ρ = −0.49, p = 0.03) and fetal HDL cholesterol (ρ = −0.46, p = 0.04) with placental fully oxidized LDL particle concentration within preterms. DISCUSSION: IUGR is a heterogeneous entity. Different pathomechanisms seem to underlie the disease in preterm and term subjects with oxidation of LDL within the placenta possibly taking place in preterm IUGRs. CONCLUSIONS: We conclude that the reduced maternal LDL cholesterol concentration in IUGR pregnancies is attributed to increased accumulation of oxidized LDL particles within the placenta at least in early onset IUGR
Assuntos
Retardo do Crescimento Fetal/metabolismo , Lipoproteínas LDL/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Placentação , Regulação para Cima , Adulto , Cesárea , HDL-Colesterol/sangue , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/patologia , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Recém-Nascido , Lipoproteínas LDL/sangue , Masculino , Oligo-Hidrâmnio/etiologia , Placenta/diagnóstico por imagem , Placenta/patologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Nascimento Prematuro , Diagnóstico Pré-Natal , Índice de Gravidade de Doença , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Oxidised low density lipoproteins (oxLDL) are key players in the development of atherosclerotic cardiovascular diseases. Since there are similarities between the pathogenesis of preeclampsia and atherosclerosis we hypothesised an increased accumulation of oxLDL at the materno-foetal and foeto-foetal interface within the placental tissue of preeclamptic women compared to women with normotensive pregnancies (controls). Moreover, we analysed maternal and foetal serum lipid parameters. PATIENTS AND METHODS: oxLDL was determined by immunohistochemistry in placental paraffin sections of 14 women suffering from preeclampsia (30th-39th week of gestation) and compared to 28 preterm and term deliveries (25th-40th week of gestation). 10 high power fields were chosen randomly by the newCAST software and oxLDL expression was analysed via standardised methods by 2 independent and blinded investigators. Maternal and foetal triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol were measured. Statistical examination was carried out by the Mann-Whitney test. RESULTS: oxLDL was found in villous trophoblast and placental endothelium. No significant differences were observed in expression intensity between preeclampsia and controls. Maternal and foetal triglyceride levels were significantly increased in preeclampsia compared to controls (pre-eclampsia mothers: 293 [SD 87.4] mg/dL, controls: 214 [SD 89.4] mg/dL, p=0.0097; preeclampsia foetuses: 26 [SD 16.6] mg/dL, controls: 18 [SD 10.4] mg/dL, p=0.0463). No significant differences in other lipid concentrations were found. CONCLUSIONS: We could not confirm our initial hypothesis of an increased oxLDL accumulation in placental tissue of preeclampsia. However, preeclampsia is a condition of dyslipidaemia affecting both maternal and foetal serum with implications for development and programming of cardiovascular diseases in later life.
Assuntos
Sangue Fetal/metabolismo , Lipídeos/sangue , Lipoproteínas LDL/sangue , Troca Materno-Fetal , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Adulto , Biomarcadores , Feminino , Humanos , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Fetal growth restriction is a serious, still poorly understood pregnancy-related pathology often associated with preeclampsia. Recent studies speculate on the role of human transthyretin, a carrier protein for thyroxin and retinol binding protein, in the etiology of both pregnancy pathologies. Objective was to investigate the localization and abundance of transthyretin (TTR) in placentas of pregnancies suffering from fetal growth restriction with and without preeclampsia and HELLP. This was a retrospective case control study on human paraffin-embedded placentas from pregnancies with a gestational age at delivery between the 24th and 34th week of gestation. 16 placentas were included in this study, 11 cases and 5 from normotensive pregnancies as controls. Cases were divided into three groups: four from early onset idiopathic intrauterine growth restriction (IUGR), four from early-onset severe preeclampsia (PE), and three from early-onset IUGR with preeclampsia plus HELLP syndrome. Distribution and abundance of TTR were investigated by means of immunohistochemistry. Semi quantitative analysis of TTR staining of placental sections revealed that TTR was mostly expressed in the villous trophoblast covering placental villi. Only weak staining of TTR in villous stroma could be detected. The comparison of placentas revealed that in pure IUGR and severe PE there is a much stronger TTR reactivity compared to controls and cases with IUGR + PE + HELLP. Concluding, the study showed that TTR is dysregulated in cases of IUGR and severe early onset preeclampsia. Interestingly, TTR expression is not affected in cases with HELLP syndrome that reveal the same staining intensities as age-matched controls.
Assuntos
Retardo do Crescimento Fetal/metabolismo , Síndrome HELLP/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Albumina/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Placenta/química , Pré-Albumina/análise , Gravidez , Estudos RetrospectivosRESUMO
Abnormalities in glucose metabolism linked to D-chiro-inostol phosphoglycans (IPGs) have been described in human placentas of preeclamptic women. In this study, a semi-quantitative approach to assess the histological assessment of IPGs revealed no significant differences between early and late onset preeclampsia and gestational age matched controls. However, there was a tendency towards higher values in early onset preeclampsia for villous stroma and placental vessels. Moreover, in control cases staining of plasma in placental vessels was present only in one part of vessels of mature intermediate villi while in preeclamptic specimens all placental vessels showed a similar staining. The tendencies of more staining in villous stroma associated with a differential staining of placental vessels only in preeclamptic specimens support a vectoral movement of D-chiro-inositol phosphoglycans from the fetus to the placenta.
Assuntos
Fosfatos de Inositol/biossíntese , Placenta/metabolismo , Polissacarídeos/biossíntese , Pré-Eclâmpsia/metabolismo , Adulto , Feminino , Idade Gestacional , Humanos , Imuno-Histoquímica , GravidezRESUMO
PURPOSE: We present a new method for noninvasive automatic measurement of perfusion intensity (PixelFlux method) in standardized 3âD power Doppler sonography to quantify differences of perfusion intensities among different placental layers. MATERIALS AND METHODS: Power Doppler sonographic videos of anterior and central placentas were recorded at various gestational ages (13 to 38 weeks) under defined conditions in 22 women with uncomplicated pregnancies which ended in the delivery of an appropriately grown fetus. Tissue perfusion intensity in four placental layers was calculated as the product of the Doppler amplitude and the perfused area encoded by power Doppler signals related to the area of the respective layer. Measurements are given as the percentage of maximal possible perfusion. RESULTS: Significant differences in placental perfusion intensities in the uterine wall (6.6â%), the maternal flow within the intervillous space (2.4â%), the fetal flow within placental villi (1.6â%) and the chorionic plate (9.3â%) were demonstrated with a continuous increase in the uterine wall and the placental villi. CONCLUSION: Placental perfusion intensity was quantified noninvasively from 3âD power Doppler signal data in an easily accomplishable manner with a new software-based measurement procedure. There are significant differences in perfusion intensities among placental layers. Placenta perfusion measurement with the PixelFlux method is feasible and can discern significant perfusion differences among different placenta layers.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Placenta/irrigação sanguínea , Ultrassonografia Doppler em Cores/métodos , Ultrassonografia Pré-Natal/métodos , Adulto , Estatura Cabeça-Cóccix , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Troca Materno-Fetal/fisiologia , Computação Matemática , Placenta/diagnóstico por imagem , Gravidez , Estudos Prospectivos , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia , SoftwareRESUMO
OBJECTIVES: The antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies (aPLs), is a leading cause for thromboembolic events, repeated miscarriage, fetal loss and is a major risk factor for fetal growth restriction (FGR) and preeclampsia. In human, anti-ß2 glycoprotein I (aß2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by aß2GPI antibodies in FGR are largely unknown. METHODS: In the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse aß2GPI monoclonal antibody. RESULTS: Administration of WBCAL-1, but not the isotype control antibody and saline, into pregnant mice specifically decreased the size of fetuses and placentas without affecting the number of delivered pups. Also, a significant increase in urinary albumin and electron microscopic changes, such as splitting layers of basal membranes in the placental labyrinth and rearrangement of pores in glomerular endothelial cells, were observed in WBCAL-1 treated mice. WBCAL-1 injection did not induce any changes in blood pressure and typical parameters of blood thromboembolic symptoms. Furthermore, FcRγ deficiency protected the fetuses from aß2GPI antibody-induced injuries. CONCLUSIONS: Our present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcRγ might be a molecular target for prevention of aß2GPI antibody-mediated obstetrical pathologies.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Retardo do Crescimento Fetal/imunologia , Receptores de IgG/fisiologia , beta 2-Glicoproteína I/imunologia , Animais , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/urina , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal/prevenção & controle , Retardo do Crescimento Fetal/urina , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Nus , Microscopia Eletrônica , Placenta/imunologia , Placenta/patologia , Gravidez , Proteinúria , Receptores de IgG/deficiênciaRESUMO
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2011 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology: 1) immunology; 2) epigenetics; 3) comparative placentation; 4) trophoblast differentiation; 5) stem cells.
Assuntos
Nível de Saúde , Placenta/fisiologia , Animais , Pesquisa Biomédica/tendências , Diferenciação Celular , Epigênese Genética , Feminino , Proteínas Fetais/genética , Proteínas Fetais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Imunomodulação , Masculino , MicroRNAs/fisiologia , Fisiologia Comparada/tendências , Placenta/citologia , Placenta/imunologia , Placentação , Gravidez , Proteínas da Gravidez/genética , Proteínas da Gravidez/metabolismo , Transplante de Células-Tronco/tendências , Células-Tronco/citologia , Células-Tronco/imunologia , Trofoblastos/citologia , Trofoblastos/imunologiaRESUMO
Preeclampsia is a multisystem disease for which the exact causes have not yet been sufficiently clarified. However, in the past few years it has become clear that a placental imbalance between angiogenic and anti-angiogenic proteins is the decisive pathogenetic factor for the occurrence of preeclampsia. With the possibility to measure these angiogenic factors (sFlt-1/PlGF ratio) in maternal blood full new diagnostic possibilities have been opened that enable the certain diagnosis or exclusion of the diseases as well as a short-term prognosis to be made. In secondary prevention the current data situation for ASA confirms a moderate but measurable utility. The management concept depends on gestational age. In the case of early clinical manifestations (< 34th week of pregnancy) the clinical management in a perinatal centre remains unchanged with foeto-maternal monitoring and induction of pulmonary maturation, symptomatic therapy under careful blood pressure lowering and determination of the optimal delivery time. A balance must be made here between foetal immaturity and maternal risks upon prolongations. The pathomechanism of anti-angiogenic overload with sFlt-1 provides a starting point for first therapeutic interventions. The present article gives an overview of current diagnostic options and presents possible future therapeutic perspectives for discussion.
RESUMO
INTRODUCTION: The cytochrome P450 (CYP)-system regulates vascular functions, inflammation, and angiogenesis that are mechanistically important in preeclampsia. OBJECTIVES: The aim of this study was to analyze the dysregulation of the Cytochrome P450 in the pathogenesis of preeclampsia. METHODS: We performed microarray screening of placenta and decidua from 25 preeclamptic women and 23 controls. Results were confirmed by realtime RT-PCR, immunohistochemistry and Serum of patients were analyzed by HPLC tandem mass spectrometry. For functional testing we did cardiomyocyte contraction bioassay and myograph studies. The reduced uterine perfusion pressure (RUPP) rat model was proceed for interventional study. RESULTS: In microarray studies the CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic decidual tissue (3.9 fold, p<0.0001) and in preeclamptic placenta (1.55 fold, p<0.001). RT-PCR confirmed the upregulation and immunohistochemistry, localized CYP2J2 in trophoblasts of villi and deciduas at week 12 and term. The CYP2J2 metabolites were analyzed by HPLC tandem mass spectrometry. 5,6- epoxyeicosatrienoic acids (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids (DHET), were elevated in preeclamptic women compared to controls in the latter two-thirds of pregnancy and after delivery. Stimulation of the trophoblast-derived cell line SGHPL-4 with the preeclampsia-associated cytokine tumor necrosis factor-a enhanced CYP2J2 gene and protein expression. For functional testing, 5,6-EET increased the beating rate of neonatal cardiomyocytes in a bioassay and downregulated large-conductance calcium-activated potassium channel KCa 1.1 activity. In the RUPP rat model of preeclampsia, we observed elevated EET, DHET, and preeclamptic features that were ameliorated by the CYP inhibitor MsPPOH. Uterine arterial rings of rats also dilated in response to MsPPOH. CONCLUSION: Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.