RESUMO
PURPOSE: Female fashion models are more at risk for developing eating disorders than non-models due to the intense occupational pressure they face. The present study focuses on assessing whether female models are more prone to report orthorexia nervosa signs and symptoms than non-models. METHODS: Female fashion models (n = 179, mean age: 25.9 SD = 4.40 years) and an age adjusted control group (n = 261, mean age: 25.0 SD = 4.97 years) were selected by snowball sampling. Participants filled out an online survey containing anthropometric questions and the 18-item Eating Habits Questionnaire. RESULTS: According to BMI, fashion models were underweight (mean BMI = 18.1 SD = 1.68) while control participants' BMI was in the normal range (mean = 22.1 SD = 4.23, p < 0.001). On all three of Eating Habits Questionnaire subscales fashion models showed significantly higher average value (Knowledge subscale: M = 2.42 among models versus M = 2.08 in the control group, p < 0.01, Cohen's d = 0.52; Problems subscale: M = 1.93 among models versus M = 2.61 in the control group, p < 0.01, Cohen's d = 0.49; Feelings subscale: M = 3.20 among models versus M = 2.96 in the control group, p < 0.01, Cohen's d = 0.38). Orthorexic tendencies were reported by 35.1% of the models versus 20.2% of controls. CONCLUSION: Fashion models are at risk for the development of eating disorders. Even though not yet included in the DSM-5, the assessment of orthorexia nervosa among fashion models seems to be important. It is suggested to take appropriate measures to prevent the spread of disordered eating habits among models as they can lead to the development of anorexia nervosa or bulimia nervosa. LEVEL OF EVIDENCE: Level III, well-designed cohort study.
Assuntos
Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Comportamento Alimentar/psicologia , Adulto , Adulto Jovem , Inquéritos e Questionários , Comportamentos Relacionados com a Saúde , Índice de Massa Corporal , Imagem Corporal/psicologia , AdolescenteRESUMO
OBJECTIVE: Sociocultural influences, including an increasing pressure for fashion models to maintain a thin body frame may be crucial in the development of eating disorders. The present study aimed to establish whether fashion models are more likely than non-models to develop eating disorders. METHODS: Female fashion models were selected by snowball sampling (n = 179, mean age: 25.9 SD = 4.70 years). They were compared with an age adjusted control group (n = 261, mean age: 25.0 SD = 4.97 years). Participants completed an online questionnaire containing the Eating Disorder Inventory. RESULTS: The average BMI of the fashion models was in the underweight range (mean BMI = 18.1 SD = 1.68). The BMI of the control group was significantly higher (mean = 22.1 SD = 4.23, p < 0.001). The frequency of simulated anorexia nervosa was 3.9% among the fashion models and 1.1% in the control group (p = 0.057). 14.6% of the models showed subclinical anorexia nervosa symptoms versus 2.7% in the control group (p < 0.001). The ratio of bulimia nervosa and subclinical bulimia nervosa showed no significant difference between the two groups. CONCLUSION: Female fashion models showed no significant difference from the control group in the frequency of anorexia nervosa and bulimia nervosa but had a significantly higher frequency of the subclinical form of anorexia nervosa.
Assuntos
Anorexia Nervosa , Bulimia Nervosa , Bulimia , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/epidemiologia , Bulimia/diagnóstico , Bulimia Nervosa/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Hábitos , HumanosRESUMO
PURPOSE: The aim of our study was validating Eating Disorder Inventory (EDI) among pregnant women, who are vulnerable to eating disorders (EDs). METHODS: In 2012-2013, 1146 women (aged 18-47 years) completed a questionnaire including EDI during the first 3 days after delivery. We checked factorial validity of three diagnostic subscales of EDI with confirmative factor analysis and internal validity by Cronbach's alpha and item-total correlation. We also tested discriminative validity by comparing average of the three subscale of EDI in case of ED and non-ED groups. RESULTS: When applying the EDI to pregnant women, it seems necessary to exclude five items on three diagnostic subscales: on the Drive for Thinness subscale, 4 items remain (out of 7); on the Bulimia subscale, 6 items remain (out of 7); the Body Dissatisfaction subscale decreases from 9 to 8 items. Cronbach's alpha and item-total correlation values meet the requirements defined by Garner et al. The internal consistency of the EDI has proved to be appropriate, indicating that it is a reliable screening tool. CONCLUSIONS: Thinking, attitudes, and behaviors connected to eating, along with the relation to altering body weight change during pregnancy. Vomiting usually accompanies pregnancy; body weight gain within wide limits is also regarded as normal during pregnancy. These behaviors and changes are not feasible to use for measuring ED symptoms. These aspects cannot be neglected when screening eating disorders in pregnant women. LEVEL OF EVIDENCE: Level IV evidence obtained from multiple time series with or without an intervention.
Assuntos
Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Adulto , Anorexia Nervosa/diagnóstico , Bulimia Nervosa/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Inventário de Personalidade , Gravidez , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
Plant-based diet is an old-new trend in nutrition. In this review based on a historical context, we wish to introduce this popular nutritional trend. Our aim is to present plant-based diet as a primary measure for prevention. We intend to critically analyse some past stereotypes related to plant-based diet - whose main components include fruits, vegetables, whole grains, legumes, nuts and seeds - according to the literature (e.g. protein, vitamin B12, folic acid, and iron intake) by doing so we wish to create an adequate conceptual basis for its interpretation. We discuss positive physiological effects of plant-based diet and its possible role in diseases risk reduction. Cardiovascular and metabolic diseases developing due to obesity could be prevented by a properly compiled plant-based diet. For patients with cancer minimizing the intake of foods of animal origin - as opposed to plant-based ones - has proved to have positive effects. Our review suggests this diet can be used in a number of diseases and it also provides long-term sustainable solutions for the health care challenges of the newest era. Orv. Hetil., 2016, 157(47), 1859-1865.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Vegetariana/normas , Preferências Alimentares , Estado Nutricional , Doença Crônica/prevenção & controle , Frutas , Nível de Saúde , Humanos , Nozes , Fatores de Risco , VerdurasRESUMO
Eating disorders are psychosomatic disorders affecting primarily women, and influence reproductive functions as well. They have an impact on ovarial cyclem fertility, course of pregnancy, process of delivery, post partum period. Moreover, some data show that they can influence the adult health status. Extensive research from the last three decades call the attention to the fact that besides the classical eating disorders (anorexia nervosa and bulimia nervosa) the newer types (e.g., orthorexia nervosa), and subclinical disorders also occur in a subgroup of pregnant women. For this reason it is of key importance that the personnel working in the territory of obstetrics and gynecology have a solid knowledge about the symptoms, screening and therapeutical opportunities, and outcome of these disorders. The review summarizes the recent research data about the relationship of eating disorders and pregnancy.
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Transtornos da Alimentação e da Ingestão de Alimentos , Complicações na Gravidez , Adulto , Feminino , Humanos , GravidezRESUMO
BACKGROUND: For a better differential diagnosis of eating disorders, it is necessary to investigate their subtypes and develop specific assessment tools to measure their specific symptoms. Orthorexia nervosa is an alleged eating disorder in which the person is excessively preoccupied with healthy food. The ORTO-15, designed by Donini and colleagues, is the first and only at least partially validated instrument to measure this construct. The aims of the present study were to examine the psychometric properties of its Hungarian adaptation (ORTO-11-Hu), and to investigate its relationship to food consumption and lifestyle habits in order to contribute to a better description of the phenomenon. METHODS: The ORTO-11-Hu, a lifestyle habits questionnaire, a food choice list indicating foods the participants choose to consume, and ten additional orthorexia-related questions were administered to a group of 810 Hungarian participants (89.4% female) aged between 20 and 70 (M = 32.39 ± 10.37 years). RESULTS: Confirmatory factor analysis suggested a single factor structure for the 11-item shortened version of the instrument. Internal consistency of the measure was adequate (Cronbach's alpha = 0.82). No significant differences were found between males and females on the ORTO-11-Hu. Age and body mass index were significantly associated with a tendency towards orthorexia nervosa. Additional orthorexia-related features were significantly correlated with ORTO-11-Hu scores: orthorexia nervosa tendency was associated not only with healthier food choices (eating more whole wheat cereals, less white wheat cereals, more fruit and vegetables) but with shopping in health food stores, as well as with some healthy lifestyle habits (more sports activity, specific dietary behaviors, and less alcohol intake). Individuals with higher orthorexia nervosa tendency also reported a greater tendency to advocate their healthy diet to their friends and family members. CONCLUSIONS: These results provide evidence for the reliability of ORTO-11-Hu and some support for the construct validity of the instrument. The present study also contributes to the establishment of (diagnostic) criteria for this new subtype of eating disorders.
Assuntos
Comportamento de Escolha , Dieta/efeitos adversos , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Comportamentos Relacionados com a Saúde , Inquéritos e Questionários , Adulto , Índice de Massa Corporal , Análise Fatorial , Feminino , Humanos , Hungria , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Adulto JovemRESUMO
AIM: To review the literature on the prevalence, risk groups and risk factors of the alleged eating disorder orthorexia nervosa. METHODS: We searched Medline and Pubmed using several key terms relating to orthorexia nervosa (ON) and checked the reference list of the articles that we found. Attention was given to methodological problems in these studies, such as the use of non-validated assessment instruments, small sample size and sample characteristics, which make generalization of the results impossible. RESULTS: Eleven studies were found. The average prevalence rate for orthorexia was 6.9 % for the general population and 35-57.8 % for high-risk groups (healthcare professionals, artists). Dieticians and other healthcare professionals are at high risk of ON. Risk factors include obsessive-compulsive features, eating-related disturbances and higher socioeconomic status. Relevant clinical experience, published literature and research data have increased in the last few years. DISCUSSION: The definition and diagnostic criteria of ON remain unclear. Further studies are needed to clarify appropriate diagnostic methods and the place of ON among psychopathological categories.
Assuntos
Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Comportamentos Relacionados com a Saúde , Humanos , Prevalência , Fatores de Risco , Classe SocialRESUMO
The place of orthorexia nervosa (ON)--described by Bratman in 1997--is not clearly defined in the diagnostic systems. However, the increasing number of clinical experiences and research data gives us more and more information about the epidemiology, and the social and individual characteristics of ON. The general population shows a 6.9% prevalence of ON; healthcare professionals are at high risk of ON with the prevalence rate of 35-57.6%. Education, the choice of profession, socioeconomic status and the internalization of the ideals of society are significant factors in the development of ON, while sex, age and body mass index do not seem to be determining variables in this respect. The lack of common criteria and proper research results on ON makes it impossible to generalize data on the general population. Further studies with larger representative samples and assessment instruments with good psychometric properties are necessary to make research data on ON comparable.
Assuntos
Anorexia Nervosa/diagnóstico , Anorexia Nervosa/epidemiologia , Comportamento Alimentar , Comportamentos Relacionados com a Saúde , Pessoal de Saúde/estatística & dados numéricos , Classe Social , Comorbidade , Diagnóstico Diferencial , Escolaridade , Humanos , Hungria/epidemiologia , Ciências da Nutrição/educação , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Over recent decades, the practice of human resource management in the transitional countries of Eastern Europe and in Hungary has changed significantly. Especially in local subsidiaries of foreign-owned companies and in the leading domestic large organizations, HRM has become a strategic function, while in the practice of small and medium-sized enterprises it is less common. COVID-19 hit companies, institutions and individuals unexpectedly, not only in Hungary but also in the more developed regions of the world. This crisis has also highlighted the fact that larger and better prepared organizations and public institutions have found it easier to weather this global human catastrophe. We analyze how the key tasks of HRM have changed during the successive waves, along four hypotheses. Initially, health protection, communication and home-office organization were the focus of the work of human resource professionals. In the second and third waves, securing and retaining staff became more important.
Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Hungria/epidemiologia , Pandemias/prevenção & controle , Pesquisa Empírica , Europa OrientalRESUMO
Introduction and aim: The of this research was to conduct a network meta-analysis based on a systematic literature search to compare the relative frequency of urinary tract infections using sodium-glucose cotransporter-2 (SGLT2) inhibitors combined with metformin in the therapy of type 2 diabetes. Method: MEDLINE and EMBASE databases were searched to identify publications of randomized, controlled trials investigating SGLT2 inhibitors combined with metformin in the therapy of type 2 diabetes and providing information on the frequency of urinary tract infections. Results: 10 165 unique citations were screened to identify 10 publications to be included in the network meta-analysis. The network meta-analysis showed reduced risk of urinary tract infections for low-dose ertugliflozin compared to other SGLT2 inhibitors (ertugliflozin 5 mg vs. empagliflozin 10 mg: RR: 0.606, 95% CrI: 0.264-1.415; ertugliflozin 5 mg vs. dapagliflozin 10 mg: RR = 0.853, 95% CrI: 0.301-2.285). For high-dose comparisons, empagliflozin 25 mg showed reduced risk of urinary tract infections compared to both ertugliflozin 15 mg (RR = 0.745, 95% CrI 0.330-1.610) and dapagliflozin 10 mg (RR = 0.680, 95% CrI: 0.337-1.289). The difference between active substances and their doses was not statistically significant for the relative frequency of urinary tract infections. The meta-regression revealed a statistically significant association between baseline fasting plasma glucose level and relative frequency of urinary tract infections (ß = 0.785, 95% CrI: 0.062-1.587). Conclusion: There was no statistically significant difference between SGLT2 inhibitors investigated in this study in terms of the relative frequency of urinary tract infections. This research demonstrates the applicability of network meta-analyses when assessing the relative effectiveness and safety of interventions. Orv Hetil. 2020; 161(13): 491-501.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/administração & dosagem , Metformina/uso terapêutico , Proteínas de Transporte de Sódio-Glucose/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose , Infecções Urinárias/epidemiologia , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND AIMS: There are contradictory findings on time changes in the prevalence of eating disorders (EDs). The first epidemiological studies in Hungary were carried out in the late 1980s. The objective of the present study was to follow the changes in the prevalence of EDs in medical students after a period of 22 years. METHODS: A questionnaire survey was conducted in 1989 and in 2010. The sample comprised medical students: 538 subjects (248 males and 290 females) in 1989 and 969 subjects (261 males and 708 females) in 2010. The questionnaire contained sociodemographic and anthropometric items, the Eating Behaviour Severity Scale, the General Health Questionnaire, the Anorexia Nervosa Inventory for Self-Rating, and the Eating Disorder Inventory (EDI). In the second wave, three subscales of the EDI-2 and the SCOFF questionnaire were added. RESULTS: Current and desired body mass index were significantly higher in the second study. Binge eating at least once a week was reported less frequently (2.7% vs 6.8% in males, 6.1% vs 13% in females) in 2010. The proportion of subclinical anorexia nervosa was higher among females in 2011 (2.5% vs 0.3%, P < 0.01). Among males, the proportion of counterregulatory behaviours increased significantly (from 8.9 to 14.6%). DISCUSSION AND CONCLUSIONS: The increase of the proportion of subclinical anorexia nervosa and that of male EDs may relate to the importance of the changes in the sociocultural background. Further representative studies are proposed in other countries of Central and Eastern Europe among medical students and in the general population.
Assuntos
Anorexia Nervosa , Bulimia , Transtornos da Alimentação e da Ingestão de Alimentos , Estudantes de Medicina , Anorexia Nervosa/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Hungria/epidemiologia , MasculinoRESUMO
INTRODUCTION: Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications. METHODS: We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring. RESULTS: PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia. DISCUSSION: PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.
Assuntos
Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Proteínas da Gravidez/metabolismo , Adulto , Cromatografia Líquida , Feminino , Humanos , Espectrometria de Massas , Gravidez , ProteômicaRESUMO
Amadori peptides were enriched using boronate affinity tips and measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). As demonstrated by electrochemical measurements, the tips show the highest binding efficiency for glucose at pH 8.2 employing ammonium chloride/ammonia buffer with ionic strength of 150 mM, exceeding taurine buffer at the same concentration. The bound constituents were released by sorbitol and formic acid. It was also demonstrated that elution with sorbitol at 1.2 M is superior to acidic media. Comparison of results was based on the numbers of detected peptides and their glycated sites. Using sorbitol for elution requires desalting prior to analysis. Therefore, three different sorbents were tested: fullerene-derivatized silica, ZipTip (C18), and C18 silica. Fullerene-derivatized silica and ZipTip showed the same performance regarding the numbers of glycated peptides, and sites were better than C18 silica. The elaborated off-line method was compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurements, by which considerable less modified peptides were detected. Affinity tips used under optimized conditions were tested for the analysis of human serum albumin (HSA) from sera of healthy and diabetic individuals. A peptide with a mass of 1783.9 Da could be detected only in samples of diabetic patients and, therefore, could be a very interesting biomarker candidate.
Assuntos
Cromatografia de Afinidade/métodos , Glicopeptídeos/química , Glicopeptídeos/isolamento & purificação , Glicoproteínas/química , Peptídeos/isolamento & purificação , Ácidos Borônicos/química , Cromatografia de Afinidade/instrumentação , Humanos , Estrutura Molecular , Peptídeos/química , Ribonuclease Pancreático/análise , Albumina Sérica/análiseRESUMO
SPE plays a crucial role in bioanalytical research. In the present work a novel fullerene(C60)-derivatised silica material is compared with octadecyl(C18) - and triaconthyl(C30)-silicas regarding recoveries of peptides and sequence coverage of HSA and fibrinogen digests. C30- and C60(30 nm)-SPE materials were found to be the two most prominent SPE materials. At low peptide concentrations C60-material prepared from a silica gel with a pore size of 30 nm has proven to be the best material with regards to recoveries. By increasing the amount of loaded peptides recoveries decrease due to its relative low binding capacity in contrast to C30-silica particles, showing no changes. The best sequence coverages of Aalpha- and Bbeta-chains of 20 pmol fibrinogen digest can also be achieved using these two SPE materials, C60 (30 nm) demonstrates an outstanding value of sequence coverage (62.15%) achieved for the gamma-chain. After nonenzymatic glycation the digests of fibrinogen and HSA were also separated. This makes the detection of a considerably higher number of glycated peptides possible compared to the unfractionated digests and the use of boronate affinity chromatography in the case of fibrinogen. For HSA, ten new sites of glycation at lysine and arginine residues have been explored. Using the detailed SPE/off-line MALDI method the glycation sites on fibrinogen are first described in this paper.
Assuntos
Fibrinogênio/análise , Fulerenos/química , Fragmentos de Peptídeos/análise , Albumina Sérica/análise , Dióxido de Silício/química , Extração em Fase Sólida/métodos , Tripsina/metabolismo , Ácidos Borônicos , Cromatografia de Afinidade , Fibrinogênio/metabolismo , Glicosilação , Humanos , Fragmentos de Peptídeos/química , Albumina Sérica/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
INTRODUCTION: Placental Protein 5 (PP5)/Tissue Factor Pathway Inhibitor-2 (TFPI-2) is an extracellular matrix-associated protein mainly expressed by the syncytiotrophoblast that may regulate trophoblast invasion. Our aim was to study placental PP5/TFPI-2 expression and its relation to placental pathology in various forms of preeclampsia and HELLP syndrome. METHODS: Placental and maternal blood specimens were collected at the time of delivery from the same women in the following groups: 1) early controls; 2) early preeclampsia; 3) early preeclampsia with HELLP syndrome; 4) late controls; and 5) late preeclampsia. After histopathological examination, placental specimens were immunostained with polyclonal anti-PP5/TFPI-2 antibody on Western blot and tissue microarray immunohistochemistry. Placental PP5/TFPI-2 immunoscores were assessed manually and with a semi-automated method. Maternal sera were immunoassayed for PP5/TFPI-2. RESULTS: PP5/TFPI-2 was localized to the cytoplasm of syncytiotrophoblast. Manual and semi-automated PP5/TFPI-2 immunoscores were higher in early preeclampsia with or without HELLP syndrome but not in late preeclampsia than in respective controls. In patients with preeclampsia, the correlation of placental PP5/TFPI-2 expression with maternal vascular malperfusion score of the placenta was positive while it was negative with birthweight and placental weight. Maternal serum PP5/TFPI-2 concentration was higher in early preeclampsia and it tended to be higher in early preeclampsia with HELLP syndrome than in early controls. DISCUSSION: Our findings suggest that an increased placental PP5/TFPI-2 expression may be associated with abnormal placentation in early preeclampsia, with or without HELLP syndrome.
Assuntos
Glicoproteínas/metabolismo , Síndrome HELLP/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Síndrome HELLP/patologia , Humanos , Placenta/patologia , Placentação , Pré-Eclâmpsia/patologia , GravidezRESUMO
Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This sine qua non of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes. To gain insights into these molecular pathways, we employed a systems biology approach and integrated different "omics," clinical, placental, and functional data from patients with distinct phenotypes of preeclampsia. First trimester maternal blood proteomics uncovered an altered abundance of proteins of the renin-angiotensin and immune systems, complement, and coagulation cascades in patients with term or preterm preeclampsia. Moreover, first trimester maternal blood from preterm preeclamptic patients in vitro dysregulated trophoblastic gene expression. Placental transcriptomics of women with preterm preeclampsia identified distinct gene modules associated with maternal or fetal disease. Placental "virtual" liquid biopsy showed that the dysregulation of these disease gene modules originates during the first trimester. In vitro experiments on hub transcription factors of these gene modules demonstrated that DNA hypermethylation in the regulatory region of ZNF554 leads to gene down-regulation and impaired trophoblast invasion, while BCL6 and ARNT2 up-regulation sensitizes the trophoblast to ischemia, hallmarks of preterm preeclampsia. In summary, our data suggest that there are distinct maternal and placental disease pathways, and their interaction influences the clinical presentation of preeclampsia. The activation of maternal disease pathways can be detected in all phenotypes of preeclampsia earlier and upstream of placental dysfunction, not only downstream as described before, and distinct placental disease pathways are superimposed on these maternal pathways. This is a paradigm shift, which, in agreement with epidemiological studies, warrants for the central pathologic role of preexisting maternal diseases or perturbed maternal-fetal-placental immune interactions in preeclampsia. The description of these novel pathways in the "molecular phase" of preeclampsia and the identification of their hub molecules may enable timely molecular characterization of patients with distinct preeclampsia phenotypes.
Assuntos
Doenças Placentárias , Pré-Eclâmpsia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Doenças Placentárias/sangue , Doenças Placentárias/genética , Doenças Placentárias/fisiopatologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteômica , Biologia de Sistemas , Trofoblastos/metabolismo , Trofoblastos/patologiaRESUMO
Preterm preeclampsia is associated with the failure of trophoblast invasion, placental hypoxic/ischemic injury and the release of toxic substances, which promote the terminal pathway of preeclampsia. In term preeclampsia, factors yet unknown trigger the placenta to induce the terminal pathway. The contribution of the villous trophoblast to these pathologic events has not been fully elucidated. Here we aimed to study how stress and signaling pathways influence trophoblastic functions in various subforms of preeclampsia. Tissue microarrays (TMAs) were constructed from placentas obtained from pregnant women in the following groups: 1-2) preterm preeclampsia with (n = 8) or without (n = 7) HELLP syndrome; 3) late-onset preeclampsia (n = 8); 4-5) preterm (n = 5) and term (n = 9) controls. TMA slides were stained for phosphorylated Akt-1, ERK1/2, JNK, and p38 kinases, and trophoblastic immunostainings were semi-quantitatively evaluated. BeWo cells were kept in various stress conditions, and the expression of FLT1, GCM1, LEP, and PGF was profiled by qRT-PCR, while Akt-1, ERK1/2, JNK, and p38 kinase activities were measured with phospho-kinase immunoassays. We found that: 1) Placental LEP and FLT1 expression was up-regulated in preterm preeclampsia with or without HELLP syndrome compared to controls; 2) Mean pp38 immunoscore was higher in preterm preeclampsia, especially in cases with HELLP syndrome, than in controls. 3) Mean pERK1/2 immunoscore was higher in preterm preeclampsia with HELLP syndrome than in controls. 4) In BeWo cells, ischemia up-regulated LEP expression, and it increased JNK and decreased ERK1/2 activity. 5) Hypoxia up-regulated FLT1 and down-regulated PGF expression, and it increased ERK1/2, JNK and p38 activity. 6) IL-1ß treatment down-regulated PGF expression, and it increased JNK and p38 activity. 7) The p38 signaling pathway had the most impact on LEP, FLT1 and PGF expression. In conclusion, hypoxic and ischemic stress, along with unknown factors, activates trophoblastic p38 signaling, which has a key role in villous trophoblastic functional changes in preterm preeclampsia. The activation of ERK1/2 signaling may induce additional trophoblastic functional changes in HELLP syndrome, while distinct mechanisms may promote late-onset preeclampsia.
Assuntos
Vilosidades Coriônicas/metabolismo , Síndrome HELLP/metabolismo , Sistema de Sinalização das MAP Quinases , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células Cultivadas , Vilosidades Coriônicas/patologia , Feminino , Regulação da Expressão Gênica , Síndrome HELLP/genética , Síndrome HELLP/patologia , Humanos , Hipóxia/fisiopatologia , Técnicas Imunoenzimáticas , Recém-Nascido , Isquemia/fisiopatologia , Placenta/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Gravidez , Nascimento Prematuro , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Trofoblastos/patologiaRESUMO
Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n = 8); (2) early-onset preeclampsia without (n = 7) and (3) with HELLP syndrome (n = 8); (4) preterm controls (n = 5); and (5) term controls (n = 9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n = 49) and controls (n = 32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p = 0.0001) and early-onset preeclampsia with or without HELLP syndrome (p = 0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.
Assuntos
Síndrome HELLP/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Sindecana-1/metabolismo , Actinas/efeitos dos fármacos , Actinas/metabolismo , Adulto , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Feminino , Humanos , Técnicas In Vitro , Gravidez , Tiazolidinas/farmacologia , Trofoblastos/citologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismoRESUMO
Several lines of evidence support the hypothesis that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of pre-eclampsia (PE). VEGF is a key component in the regulation of vascular remodelling and the survival of cytotrophoblasts in the placenta. In this case-control study, we aimed to test whether VEGF genetic polymorphisms are associated with the risk of severe PE. We enrolled 84 nulliparous pregnant women with severe PE (PE group). Their VEGF G(+405)C and VEGF C(-2578)A genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) from venous blood samples and were compared with the corresponding VEGF genotypes of 96 nulliparous patients with uncomplicated pregnancies (control group). Carriers of the VEGF(+405)G allele occurred less frequently in PE than in the control group [P = 0.039; adjusted odds ratio (aOR) = 0.28, range: 0.08-0.93]. Hypertension and proteinuria were diagnosed earlier (by 1.6 weeks and 1.9 weeks, respectively) in PE patients with VEGF(-2578)A only after adjustment of this association for risk factors of PE. Our results suggest that carriers of VEGF(+405)G allele have a decreased susceptibility to PE and that the progression of PE may be modified by the presence of VEGF(-2578)A allele. Nevertheless, the clinical significance of these findings remains to be determined.