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1.
Mol Nutr Food Res ; 68(2): e2300533, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38085123

RESUMO

BACKGROUND: Human milk oligosaccharides (HMOs) are bioactive glycans first detected in human milk. Their presence in maternal blood during pregnancy suggests systemic functions. Dynamics and associations of the most abundant prenatal HMOs in relation to maternal BMI and serum lipids in a cohort of 87 pregnant women with either overweight or obesity are studied. METHODS: Serum HMOs (2'FL, 3'SL, 3'SLN, LDFT), serum lipids (total cholesterol, HDL, LDL, triglycerides), and BMI are measured at 15, 24, and 32 weeks of gestation. RESULTS: 2'FL and LDFT are negatively correlated to pre-pregnancy BMI and increase significantly slower between 15 and 24 weeks in highly obese women. Women without detectable increase of serum 2'FL (non-secretors) show a less pronounced gestational weight gain and lower BMI in the third trimester as compared to women phenotype as secretors. Higher early-pregnancy 2'FL is associated with high HDL and low triglycerides in pregnancy. On the other hand, higher 3'SL at 15 weeks is associated with higher triglycerides, LDL, and total cholesterol. CONCLUSIONS: Higher early-pregnancy 2'FL is associated with a cardioprotective lipid profile, whereas higher 3'SL is associated with an atherogenic lipid profile. Serum trajectories of 2'FL and LDFT in obese women suggest an obesity mediated delay of α-1,2-fucosylation.


Assuntos
Ganho de Peso na Gestação , Leite Humano , Humanos , Feminino , Gravidez , Sobrepeso , Gestantes , Índice de Massa Corporal , Oligossacarídeos , Obesidade , Vitaminas , Triglicerídeos , Lipídeos
2.
Cell Biosci ; 13(1): 163, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684702

RESUMO

BACKGROUND: The human placenta, a tissue with a lifespan limited to the period of pregnancy, is exposed to varying shear rates by maternal blood perfusion depending on the stage of development. In this study, we aimed to investigate the effects of fluidic shear stress on the human trophoblast transcriptome and metabolism. RESULTS: Based on a trophoblast cell line cultured in a fluidic flow system, changes caused by shear stress were analyzed and compared to static conditions. RNA sequencing and bioinformatics analysis revealed an altered transcriptome and enriched gene ontology terms associated with amino acid and mitochondrial metabolism. A decreased GLUT1 expression and reduced glucose uptake, together with downregulated expression of key glycolytic rate-limiting enzymes, hexokinase 2 and phosphofructokinase 1 was observed. Altered mitochondrial ATP levels and mass spectrometry data, suggested a shift in energy production from glycolysis towards mitochondrial oxidative phosphorylation. This shift in energy production could be supported by increased expression of glutamic-oxaloacetic transaminase variants in response to shear stress as well as under low glucose availability or after silencing of GLUT1. The shift towards amino acid metabolic pathways could be supported by significantly altered amino acid levels, like glutamic acid, cysteine and serine. Downregulation of GLUT1 and glycolytic rate-limiting enzymes, with concomitant upregulation of glutamic-oxaloacetic transaminase 2 was confirmed in first trimester placental explants cultured under fluidic flow. In contrast, high fluid shear stress decreased glutamic-oxaloacetic transaminase 2 expression in term placental explants when compared to low flow rates. Placental tissue from pregnancies with intrauterine growth restriction are exposed to high shear rates and showed also decreased glutamic-oxaloacetic transaminase 2, while GLUT1 was unchanged and glycolytic rate-limiting enzymes showed a trend to be upregulated. The results were generated by using qPCR, immunoblots, quantification of immunofluorescent pictures, padlock probe hybridization, mass spectrometry and FRET-based measurement. CONCLUSION: Our study suggests that onset of uteroplacental blood flow is accompanied by a shift from a predominant glycolytic- to an alternative amino acid converting metabolism in the villous trophoblast. Rheological changes with excessive fluidic shear stress at the placental surface, may disrupt this alternative amino acid pathway in the syncytiotrophoblast and could contribute to intrauterine growth restriction.

3.
Front Med (Lausanne) ; 10: 1208103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37746089

RESUMO

Background: Postpartum hemorrhage (PPH) is still the leading cause of maternal morbidity and mortality worldwide. While impaired fibrin polymerization plays a crucial role in the development and progress of PPH, recent approaches using viscoelastic measurements have failed to sensitively detect early changes in fibrinolysis in PPH. This study aimed to evaluate whether women experiencing PPH show alterations in POC-VET fibrinolytic potential during childbirth and whether fibrinolytic potential offers benefits in the prediction and treatment of PPH. Methods: Blood samples were collected at three different timepoints: T0 = hospital admission (19 h ± 18 h prepartum), T1 = 30-60 min after placental separation, and T2 = first day postpartum (19 h ± 6 h postpartum). In addition to standard laboratory tests, whole-blood impedance aggregometry (Multiplate) and viscoelastic testing (VET) were performed using the ClotPro system, which included the TPA-test lysis time, to assess the POC-VET fibrinolytic potential, and selected coagulation factors were measured. The results were correlated with blood loss and clinical outcome markers. Severe PPH was defined as a hemoglobin drop > 4g/dl and/or the occurrence of shock or the need for red blood cell transfusion. Results: Blood samples of 217 parturient women were analyzed between June 2020 and December 2020 at Heidelberg University Women's Hospital, and 206 measurements were eligible for the final analysis. Women experiencing severe PPH showed increased fibrinolytic potential already at the time of hospital admission. When compared to non-PPH, the difference persisted 30-60 min after placental separation. A higher fibrinolytic potential was accompanied by a greater drop in fibrinogen and higher d-dimer values after placental separation. While 70% of women experiencing severe PPH showed fibrinolytic potential, 54% of those without PPH showed increased fibrinolytic potential as well. Conclusion: We were able to show that antepartal and peripartal fibrinolytic potential was elevated in women experiencing severe PPH. However, several women showed high fibrinolytic potential but lacked clinical signs of PPH. The findings indicate that high fibrinolytic potential is a risk factor for the development of coagulopathy, but further conditions are required to cause PPH.

4.
Nutrients ; 15(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37764825

RESUMO

(1) Background: Pregnancy presents a challenge to maternal glucose homeostasis; suboptimal adaptations can lead to gestational diabetes mellitus (GDM). Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. We thus assessed the HMO response to glucose load during an oral glucose tolerance test (OGTT) and investigated HMO associations with glucose tolerance/insulin sensitivity in healthy pregnant women. (2) Methods: Serum of 99 women, collected at 0 h, 1 h and 2 h during a 75 g OGTT at 24-28 gestational weeks was analyzed for HMOs (2'FL, 3'SLN, LDFT, 3'SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results: Serum 3'SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3'SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions: Rapid increase in serum 3'SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy. Underlying mechanisms or potential consequences of observed HMO changes remain to be elucidated.


Assuntos
Diabetes Gestacional , Resistência à Insulina , Gravidez , Humanos , Feminino , Glucose , Leite Humano , Glicemia , Peptídeo C , Oligossacarídeos , Insulina
5.
BMC Pregnancy Childbirth ; 23(1): 653, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689629

RESUMO

BACKGROUND: Pregnant women have an increased risk of getting infected with SARS-CoV-2 and are more prone to severe illness. Data on foetal demise in affected pregnancies and its underlying aetiology is scarce and pathomechanisms remain largely unclear. CASE: Herein we present the case of a pregnant woman with COVID-19 and intrauterine foetal demise. She had no previous obstetric or gynaecological history, and presented with mild symptoms at 34 + 3 weeks and no signs of foetal distress. At 35 + 6 weeks intrauterine foetal death was diagnosed. In the placental histopathology evaluation, we found inter- and perivillous fibrin depositions including viral particles in areas of degraded placental anatomy without presence of viral entry receptors and SARS-CoV-2 infection of the placenta. CONCLUSION: This case demonstrates that maternal SARS-CoV-2 infection in the third trimester may lead to an unfavourable outcome for the foetus due to placental fibrin deposition in maternal COVID-19 disease possibly via a thrombogenic microenvironment, even when the foetus itself is not infected.


Assuntos
COVID-19 , Insuficiência Placentária , Gravidez , Feminino , Humanos , Insuficiência Placentária/etiologia , COVID-19/complicações , Placenta , SARS-CoV-2 , Natimorto , Fibrina
8.
World J Hepatol ; 15(7): 904-913, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37547032

RESUMO

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a rare but severe complication for both the mother and the unborn child. The diagnosis is primarily based on elevated serum levels of bile acids. In a large ICP cohort, we here study in detail liver stiffness (LS) using transient elastography (TE), now widely used to non-invasively screen for liver cirrhosis within minutes. AIM: To specifically explore LS in a large cohort of women with ICP compared to a control group with uncomplicated pregnancy. METHODS: LS and hepatic steatosis marker controlled attenuation parameter (CAP) were measured in 100 pregnant women with ICP using TE (Fibroscan, Echosens, Paris, France) between 2010 and 2020. In 17 cases, LS could be measured postpartum. 450 women before and 38 women after delivery with uncomplicated pregnancy served as control group. Routine laboratory, levels of bile acids and apoptosis marker caspase-cleaved cytokeratin 18 fragment (M30) were also measured. RESULTS: Women with ICP had significantly elevated transaminases but normal gamma-glutamyl transferase (GGT). Mean LS was significantly increased at 7.3 ± 3.0 kPa compared to the control group at 6.2 ± 2.3 kPa (P < 0.0001). Postpartum LS decreased significantly in both groups but was still higher in ICP (5.8 ± 1.7 kPa vs 4.2 ± 0.9 kPa, P < 0.0001), respectively. In ICP, LS was highly significantly correlated with levels of bile acids and M30 but not transaminases. No correlation was seen with GGT that even increased significantly after delivery in the ICP group. Bile acids were mostly correlated with the liver apoptosis marker M30, LS and levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin. In multivariate analysis, LS remained the sole parameter that was independently associated with elevated bile acids. CONCLUSION: In conclusion, LS is significantly elevated in ICP which is most likely due to toxic bile acid accumulation and hepatocyte apoptosis. In association with conventional laboratory markers, LS provides additional non-invasive information to rapidly identify women at risk for ICP.

9.
F S Rep ; 4(2): 231-234, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37398607

RESUMO

Objective: To report a case of monozygotic dichorionic (DC) twins after a single cryopreserved blastocyst embryo transfer followed by genetic determination of zygosity postpartum. Design: Case report. Setting: University hospital. Patients: A 26-year-old woman with polycystic ovary syndrome and her 36-year-old male partner with severe oligozoospermia, resulting in a 1.5-year history of primary infertility. Interventions: Controlled ovarian stimulation and intracytoplasmic sperm injection treatment with single cryopreserved embryo transfer at blastocyst stage. Main Outcome Measures: Ultrasound images of the fetuses and short tandem repeat genotyping postpartum. Results: A DC twin pregnancy following a single cryopreserved blastocyst embryo transfer was confirmed at the first trimester screening. Confirmatory testing performed postpartum included short tandem repeat analysis determining monozygosity and pathology examination reporting DC placental configuration. Conclusions: Dichorionic monozygotic twins are thought to arise from the splitting of an embryo before the blastocyst stage. This case suggests that placental configuration of monozygotic twins may not strictly depend on timing of embryo division. Genetic analysis is the only tool to confirm the zygosity.

10.
Front Cell Dev Biol ; 11: 1183793, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325567

RESUMO

Tissue insults in response to inflammation, hypoxia and ischemia are accompanied by the release of ATP into the extracellular space. There, ATP modulates several pathological processes, including chemotaxis, inflammasome induction and platelet activation. ATP hydrolysis is significantly enhanced in human pregnancy, suggesting that increased conversion of extracellular ATP is an important anti-inflammatory process in preventing exaggerated inflammation, platelet activation and hemostasis in gestation. Extracellular ATP is converted into AMP, and subsequently into adenosine by the two major nucleotide-metabolizing enzymes CD39 and CD73. Here, we aimed to elucidate developmental changes of placental CD39 and CD73 over gestation, compared their expression in placental tissue from patients with preeclampsia and healthy controls, and analyzed their regulation in response to platelet-derived factors and different oxygen conditions in placental explants as well as the trophoblast cell line BeWo. Linear regression analysis showed a significant increase in placental CD39 expression, while at the same time CD73 levels declined at term of pregnancy. Neither maternal smoking during first trimester, fetal sex, maternal age, nor maternal BMI revealed any effects on placental CD39 and CD73 expression. Immunohistochemistry detected both, CD39 and CD73, predominantly in the syncytiotrophoblast layer. Placental CD39 and CD73 expression were significantly increased in pregnancies complicated with preeclampsia, when compared to controls. Cultivation of placental explants under different oxygen conditions had no effect on the ectonucleotidases, whereas presence of platelet releasate from pregnant women led to deregulated CD39 expression. Overexpression of recombinant human CD39 in BeWo cells decreased extracellular ATP levels after culture in presence of platelet-derived factors. Moreover, platelet-derived factors-induced upregulation of the pro-inflammatory cytokine, interleukin-1ß, was abolished by CD39 overexpression. Our study shows that placental CD39 is upregulated in preeclampsia, suggesting an increasing demand for extracellular ATP hydrolysis at the utero-placental interface. Increased placental CD39 in response to platelet-derived factors may lead to enhanced conversion of extracellular ATP levels, which in turn could represent an important anti-coagulant defense mechanism of the placenta.

11.
Geburtshilfe Frauenheilkd ; 83(5): 547-568, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37152544

RESUMO

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

12.
Geburtshilfe Frauenheilkd ; 83(5): 569-601, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37169014

RESUMO

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

13.
Eur J Obstet Gynecol Reprod Biol ; 285: 81-85, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37087834

RESUMO

OBJECTIVE: Enhanced recovery after surgery (ERAS) recommendations for cesarean section (ERAC), likely the most common reason for laparotomy in women, were issued in 2018-19. We examined how current perioperative management at cesarean section in Austrian hospitals aligns with ERAS recommendations. STUDY DESIGN: We surveyed the 21 largest public obstetric units in Austria for alignment with 20 of the 31 strong ERAS recommendations regarding perioperative maternal care at cesarean section. We also looked at how the German-language clinical guideline for cesarean section (AWMF Guideline Sectio caesarea) aligns with ERAS recommendations. RESULTS: The 21 obstetric units cared for about 51% of all births in Austria in 2019. Cesarean section rates ranged from 17.7% to 50.4%. All 21 units implemented the five strong recommendations regarding patient information and counselling, regional anesthesia, euvolemia and multimodal analgesia. The least implemented strong recommendation was the one for the use of pneumatic compression stockings to prevent thromboembolic disease (0/21 units). Overall, all 21 units implemented ≥11 and 13 (62%) implemented ≥15 (≥75%) of the 20 strong recommendations; no unit implemented all 20 strong recommendations. There were no differences in the implementation of strong recommendations according to hospital volume. CONCLUSIONS: Even in the absence of formal adoption of ERAS program for cesarean section many perioperative ERAS recommendations are already implemented in Austria. The least implemented recommendations were the use of pneumatic compression stockings (0 of 21 units) and immediate catheter removal (4 of 21 units). Only 10 of the 20 ERAS recommendations we looked at are included in the current German-language clinical guideline for cesarean section.


Assuntos
Analgesia , Cesárea , Gravidez , Feminino , Humanos , Áustria , Assistência Perioperatória , Manejo da Dor
14.
Nutrients ; 14(10)2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35631205

RESUMO

(1) Background: Human milk oligosaccharides (HMOs) are already found in maternal circulation in early pregnancy, changing with gestational age. HMOs are also present in cord blood and amniotic fluid (AF). We aimed to assess HMO profiles in AF over the course of gestation. (2) Methods: AF was collected during diagnostic amniocentesis, fetal surgery, or C-section from 77 women with a gestational age of ranging from 14.3 to 40.9 weeks. Samples were analysed using high performance liquid chromatography with fluorescence detection. (3) Results: We found lactose and up to 16 HMO structures in all AF samples investigated, starting at 14 weeks of gestation. Overall, 3'-sialyllactose (3'SL) and 2'-fucosyllactose (2'FL) were the most abundant HMOs. Individual and total HMO concentrations were significantly positively correlated with gestational age. HMO composition also changed between early, mid- and late pregnancy, with relative concentrations of 3'SL significantly decreasing (44%, 25%, 24%) and 2'FL increasing (7%, 13%, 21%), respectively. (4) Conclusion: Our study shows that HMOs are already present in AF early in pregnancy. This demonstrates extensive contact of the fetus with a broad variety of HMOs, suggesting roles for HMOs in fetal tissue development during the time course of pregnancy.


Assuntos
Líquido Amniótico , Leite Humano , Líquido Amniótico/química , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Lactente , Leite Humano/química , Oligossacarídeos/análise , Gravidez
15.
Front Pediatr ; 10: 864373, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620147

RESUMO

Background: The neonatal intensive care unit causes maternal stress and postpartum depressive symptoms in preterm and term mothers. Personal resources like maternal resilience are usually not considered in counselling these women. Objective: This study aims to evaluate the resilience and differences in postpartum depression after admission of newborns at the neonatal intensive care unit. Methods: This prospective pilot study was conducted in a single teaching hospital in Austria from December 2016 until December 2018. Sixty women completed two internationally validated questionnaires, the Edinburgh Postnatal Depression Scale (EPDS) to evaluate depressive symptoms and the Resilience Scale RS-13 to measure maternal resilience during the postpartum period (3 to 10 days postpartum). Additionally, women answered two open questions about burdens and relief. Results: Twenty women (34%) showed lower resilience scores. The 39 high-resilient women (66%) showed significantly less depression (p = 0.005). Women reported social support from their partner (n = 15), health professionals and psychologists (n = 15), family and friends (n = 12), and child-specific relief, e.g., spending time with the newborn and involvement in care (n = 7) as the most helpful variable during the first postpartum period. Conclusion: The experience of having a newborn at the neonatal intensive care unit is a challenging event for women. Women have different resilience parameters. Mothers with lower resilience will benefit from social support and emotional health-promoting activities.

16.
EMBO Mol Med ; 14(4): e14990, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35253392

RESUMO

The heterogeneous response of acute myeloid leukemia (AML) to current anti-leukemic therapies is only partially explained by mutational heterogeneity. We previously identified GPR56 as a surface marker associated with poor outcome across genetic groups, which characterizes two leukemia stem cell (LSC)-enriched compartments with different self-renewal capacities. How these compartments self-renew remained unclear. Here, we show that GPR56+ LSC compartments are promoted in a complex network involving epithelial-to-mesenchymal transition (EMT) regulators besides Rho, Wnt, and Hedgehog (Hh) signaling. Unexpectedly, Wnt pathway inhibition increased the more immature, slowly cycling GPR56+ CD34+ fraction and Hh/EMT gene expression, while Wnt activation caused opposite effects. Our data suggest that the crucial role of GPR56 lies in its ability to co-activate these opposing signals, thus ensuring the constant supply of both LSC subsets. We show that CDK7 inhibitors suppress both LSC-enriched subsets in vivo and synergize with the Bcl-2 inhibitor venetoclax. Our data establish reciprocal transition between LSC compartments as a novel concept underlying the poor outcome in GPR56high AML and propose combined CDK7 and Bcl-2 inhibition as LSC-directed therapy in this disease.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Quinases Ciclina-Dependentes , Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Sulfonamidas , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteína Quinase CDC2/antagonistas & inibidores , Quinases Ciclina-Dependentes/antagonistas & inibidores , Sinergismo Farmacológico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/uso terapêutico , Sulfonamidas/farmacologia , Quinase Ativadora de Quinase Dependente de Ciclina
17.
Front Immunol ; 13: 1095879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713449

RESUMO

Hofbauer cells (HBCs) are resident macrophages of the human placenta, regulating immune tolerance and tissue homeostasis. HBCs of a normal placenta (CTR) exhibit mainly an anti-inflammatory M2 phenotype. Under exaggerated chronic inflammation during pregnancy, as in preeclampsia (PE), a phenotypic switch towards M1 polarization has been proposed. PE, defined as maternally derived syndrome can be distinguished into two different entities: early-onset (EO) preeclampsia and late-onset (LO) preeclampsia. Although the clinical presenting characteristics overlap, both can be identified by biochemical markers, heritability, and different maternal and fetal outcomes. To date, no study has specifically investigated polarization and phenotype of EO- and LO-PE HBCs and looked at possible changes in HBC functionality. Primary HBCs were isolated from CTR and PE placentae. First, in vitro morphological differences were observed between CTR and PE HBCs, with both PE groups exhibiting features of M1 macrophages alongside M2 forms. Interestingly, a different polarization pattern was observed between EO- and LO-PE HBCs. EO-PE HBCs develop a tissue remodeling M2 phenotype that is strongly shifted toward M1 polarization and showed a significant upregulation of CD86, TLR4, and HLA-DR. Furthermore, this pro-inflammatory signature is corroborated by higher expression of IRF5 and of NOS2 (p ≤ 0.05). However, their M2 characteristics is reflected by significant TGF-ß secretion and ARG1 expression. In contrast, LO-PE HBCs developed a phagocytic CD209-low M2 phenotype in which the M1 pattern was not as pronounced as they downregulated the NOS2 gene, but expressed increased levels of pro-inflammatory CD80 and TLR1 (p ≤ 0.05). The enhanced phagocytosis and MMP-9 secretion alongside the increased secretion of anti-inflammatory IL -4, IL -13 and TGF-ß in both EO- and LO-PE HBCs suggests their adaptive role and plasticity in resolving inflammation and tissue homeostasis.


Assuntos
Placenta , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/metabolismo , Macrófagos , Inflamação/metabolismo , Fator de Crescimento Transformador beta/metabolismo
18.
Transl Pediatr ; 10(8): 2225-2234, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34584893

RESUMO

Congenital heart disease (CHD) is the most common cause of major congenital anomalies affecting newborns. Prenatal detection of CHD has been improving continuously during the last two decades due to technical advances and thus optimized fetal cardiac imaging. Besides the in-utero diagnosis of CHD effective parental counseling is an integral part of any Fetal Cardiology Program. However, studies on the most effective techniques are scarce, as well as data on empirical assessment of counseling and its effectiveness. In this review article, we summarize current guidelines from different international associations and societies. We provide an updated literature overview evaluating current standards of counseling with regard to parental needs. This includes ethical aspects, counseling for univentricular disease and in-utero cardiac interventions. We discuss our method to assess counseling success for fetal heart defects by exploring different analytical dimensions that may be considered helpful in order to improve efficacy. Finally, we present a proposal of how to optimize a setting for counseling based on the current literature and our own data. In summary, parental counseling for fetal heart disease is complex and multidimensional. Significant expertise in fetal cardiology and physiology, potential progression of CHD, postnatal treatment strategies and knowledge of long-term sequelae is necessary. A structured approach, together with continuous improvement of communicative skills, may lead to more effective counseling for parents following a diagnosis of CHD in the fetus.

19.
Anaesthesist ; 70(5): 392-397, 2021 05.
Artigo em Alemão | MEDLINE | ID: mdl-33301057

RESUMO

BACKGROUND: Postdural puncture headache (PDPH) occurs in up to 11% of patients after spinal anesthesia and in more than 80% after dural perforation upon epidural anesthesia. It represents a severe anesthesiological complication in obstetric patients. If conservative medication measures do not result in a timely relief of symptoms, the current guidelines recommend the early implementation of an epidural blood patch; however, although performing an epidural blood patch is effective to treat PDPH, potential side effects include neurological complications, spinal hematoma and infections. Assumed to reduce cerebral vasodilatation as a potential pathophysiological driver of PDPH, the transnasal block of the sphenopalatine ganglion with local anesthetics is discussed as an alternative approach. METHODS: In this case study a modification of this technique is reported using a mucosal atomization device (MAD) for off-label nasal administration of lidocaine in two obstetric patients suffering from PDPH. Up to now there is no experience with this modified technique in obstetric anesthesiology. RESULTS: The first patient (25-year-old secundigravida, body mass index [BMI] 54.7 kg/m2) displayed a pronounced PDPH with nausea and vomiting during the first day after a cesarean section under spinal anesthesia (3 attempts). The second patient (32-year-old tertiagravida, BMI 27.3 kg/m2) was readmitted to hospital due to PDPH 4 days after a natural birth under epidural anesthesia. Whereas conservative measures and therapeutic attempts with nonopioid analgesics and caffeine did not result in a sufficient treatment success, intranasal lidocaine administration via a MAD led to an immediate and persisting symptom relief. Both patients could be discharged from hospital after 24 h of surveillance and did not report any relevant side effects of the lidocaine administration. CONCLUSION: The described noninvasive and simple procedure represents a valuable addition to previously known treatment options for PDPH and a potential alternative to an epidural blood patch in obstetric patients with PDPH. Prospective studies are needed to validate the findings.


Assuntos
Anestesiologia , Cefaleia Pós-Punção Dural , Administração Intranasal , Adulto , Placa de Sangue Epidural , Cesárea , Feminino , Humanos , Lidocaína , Cefaleia Pós-Punção Dural/terapia , Gravidez
20.
JACC Case Rep ; 2(1): 139-144, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34316982

RESUMO

Hypertrophic obstructive cardiomyopathy (HOCM) increases the risk for mother and fetus during pregnancy. Alcohol septal ablation (ASA) is an established procedure in nonpregnant patients with HOCM. In this report, we present a case of a 29-year-old woman in her 29th gestational week with decompensated HOCM undergoing a successful ASA. (Level of Difficulty: Advanced.).

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