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1.
Z Geburtshilfe Neonatol ; 223(6): 373-394, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31801169

RESUMO

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). 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.


Assuntos
Ruptura Prematura de Membranas Fetais , Trabalho de Parto Prematuro/prevenção & controle , Guias de Prática Clínica como Assunto , Nascimento Prematuro , Sociedades Médicas , Prevenção Terciária , Incompetência do Colo do Útero , Áustria , Feminino , Ruptura Prematura de Membranas Fetais/prevenção & controle , Ruptura Prematura de Membranas Fetais/terapia , Humanos , Recém-Nascido , Obstetrícia , Gravidez , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/terapia , Sistema de Registros
2.
Z Geburtshilfe Neonatol ; 223(5): 304-316, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31623006

RESUMO

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.


Assuntos
Guias de Prática Clínica como Assunto , Nascimento Prematuro , Áustria , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Prevenção Primária , Sistema de Registros , Prevenção Secundária , Sociedades Médicas
3.
Geburtshilfe Frauenheilkd ; 79(8): 800-812, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423016

RESUMO

Aims This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. Methods Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). Recommendations Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.

4.
Geburtshilfe Frauenheilkd ; 79(8): 813-833, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423017

RESUMO

Aims This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. Methods The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). 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.

5.
PLoS Pathog ; 14(12): e1007464, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30521644

RESUMO

The ubiquitous Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is etiologically linked to the development of several malignancies and autoimmune diseases. EBV has a multifaceted life cycle that comprises virus lytic replication and latency programs. Considering EBV infection holistically, we rationalized that prophylactic EBV vaccines should ideally prime the immune system against lytic and latent proteins. To this end, we generated highly immunogenic particles that contain antigens from both these cycles. In addition to stimulating EBV-specific T cells that recognize lytic or latent proteins, we show that the immunogenic particles enable the ex vivo expansion of cytolytic EBV-specific T cells that efficiently control EBV-infected B cells, preventing their outgrowth. Lastly, we show that immunogenic particles containing the latent protein EBNA1 afford significant protection against wild-type EBV in a humanized mouse model. Vaccines that include antigens which predominate throughout the EBV life cycle are likely to enhance their ability to protect against EBV infection.


Assuntos
Antígenos Virais/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Vacinas contra Herpesvirus/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Camundongos , Latência Viral
6.
World J Gastroenterol ; 24(38): 4393-4402, 2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30344423

RESUMO

AIM: To study liver stiffness (LS) during pregnancy and its association with complications during pregnancy. METHODS: In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device (Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women (controls) while preeclampsia and intrahepatic cholestasis of pregnancy (ICP) developed in 22 and 40 women, respectively. RESULTS: In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa (P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index (BMI). In women with pregnancy complications, LS was significantly higher as compared to controls (P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05 (1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa (P < 0.001). CONCLUSION: During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent non-invasive predictor.


Assuntos
Colestase Intra-Hepática/diagnóstico , Fígado/patologia , Pré-Eclâmpsia/diagnóstico , Complicações na Gravidez/diagnóstico , Adulto , Fosfatase Alcalina/sangue , Estudos de Casos e Controles , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/epidemiologia , Técnicas de Imagem por Elasticidade/métodos , Feminino , Alemanha/epidemiologia , Idade Gestacional , Humanos , Fígado/diagnóstico por imagem , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Prognóstico , Estudos Prospectivos , Ultrassonografia/métodos
7.
Arch Gynecol Obstet ; 298(3): 521-527, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29938346

RESUMO

PURPOSE: ß2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the ß2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other ß2-mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different ß2-sympathomimetic tocolytic drugs.


Assuntos
Fenoterol/uso terapêutico , Hemangioma/epidemiologia , Simpatomiméticos/uso terapêutico , Tocolíticos/uso terapêutico , Peso ao Nascer , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Gravidez , Estudos Retrospectivos , Tocólise
8.
Arch Gynecol Obstet ; 297(2): 505-512, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29164336

RESUMO

PURPOSE: Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are pro-inflammatory cytokines which have been shown to be involved in the pathophysiology of implantation disorders. Both cytokines in combination are able to sensitize primarily resistant human endometrial stromal cells (ESCs) to Fas-induced apoptosis. Since CCL (CC-chemokine ligand) 5 and CCL2 are important regulators of the endometrial immune cell population, we examined the impact of TNF-α and IFN-γ on these two chemokines under non-apoptotic and apoptotic conditions. METHODS: ESCs were isolated from hysterectomy specimens, decidualized in vitro and incubated with TNF-α, IFN-γ, an activating anti-Fas antibody and a caspase-inhibitor. CCL5 and CCL2 were measured using ELISA and real-time RT-PCR. Apoptosis was determined by flow cytometry, and cellular viability and membrane integrity were measured by fluorescent assays. RESULTS: The secretion of CCL5 and CCL2 was stimulated in undifferentiated and decidualized ESCs by the combination of TNF-α and IFN-γ under non-apoptotic as well as apoptotic (with Fas-stimulation in parallel) conditions. TNF-α or IFN-γ alone did not have this effect. The stimulatory influence of TNF-α plus IFN-γ on CCL5 and CCL2 in ESCs was also seen on the transcriptional level. Inhibition of cell death by a caspase-inhibitor had no influence on the secretion of CCL5 and CCL2 in ESCs under apoptotic stimulation. CONCLUSION: TNF-α and IFN-γ modulate the secretion of chemokines in ESCs independently of Fas-induced apoptosis. These results suggest a constant response pattern on pro-inflammatory cytokines within the population of human ESCs.


Assuntos
Apoptose/efeitos dos fármacos , Quimiocinas/metabolismo , Endométrio/efeitos dos fármacos , Interferon gama/farmacologia , Células Estromais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Morte Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Implantação do Embrião/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Humanos , Interferon gama/metabolismo , Células Estromais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Surg Endosc ; 32(2): 1002-1011, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28840380

RESUMO

BACKGROUND: In general surgery, minimally invasive laparoscopic procedures have been steadily increasing over the last decade. The application of advanced bipolar and ultrasonic energy devices for sealing and cutting of blood vessels plays a vital role in routine clinical procedures. The advantages of energy-based instruments are enhanced sealing capability combined with both fast sealing time and minimal thermal injury. The purpose of this study was to compare the safety and efficacy profiles of nine laparoscopic sealing and cutting devices in a porcine model, with a new scoring system. METHODS: Comparative studies in a porcine model were performed to assess vessel sealing, burst pressure, thermal spread, maximum heat, sealing/cooling time, and compression strength over the full jaw. Nine different devices from five manufacturers were tested in this study. The sealing and cutting devices (SCD) score has been developed to enable standardized comparisons of various devices. For this purpose, the most important parameters were identified through a consensus approach. RESULTS: All sealed vessels with different devices could withstand a median pressure of more than 300 mmHg (range 112-2046 mmHg). The time for the sealing procedure was 7.705 s (range 5.305-18.38 s) for the ultrasonic and 7.860 s (range 5.08-10.17 s) for the bipolar devices. The ultrasonic instruments reached a median temperature of 218.1 °C (range 81.3-349.75 °C) and the bipolar devices a temperature of 125.5 °C (range 94.1-133.35 °C). The tissue reached a median temperature of 61.9 (range 47.1-80.6 °C) after ultrasonic sealing and 76.7 °C (range 63.1-94.2 °C) after bipolar sealing. The median SCD score was 10.47 (range 7.16-13.72). CONCLUSION: All the instruments used seemed safe for use on the patient. The SCD score allows an indirect comparability of the instruments.


Assuntos
Dissecação/instrumentação , Hemostasia Cirúrgica/instrumentação , Laparoscopia/instrumentação , Animais , Desenho de Equipamento , Segurança do Paciente , Pressão , Suínos , Temperatura Ambiente , Fatores de Tempo
10.
Geburtshilfe Frauenheilkd ; 77(10): 1104-1110, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29093604

RESUMO

Background: Cancer patients have a higher risk for thromboembolic events compared to healthy individuals and are often treated with heparins. A beneficial effect of heparins on tumor patients above and beyond the classic anticoagulation effect has been reported, leading to an increased focus on the use of heparins in anticancer treatment. In recent years, it has become apparent that microenvironments greatly affect tumor development and can be a major source of tumor-promoting factors. Cytokines play an important role in tumor microenvironments, inducing carcinogenesis and influencing tumor progression by promoting angiogenesis, metastatic potential and immunosuppression. The possible interaction of heparins and cytokines could also have an effect on cancer cells. Methods: This study investigated the effect of paclitaxel (PTX) combined with heparins on the vitality of endometrial cancer cells using viability and cytotoxicity assays. The study also examined whether treatment with paclitaxel and heparin influences cytokine secretion or expression. Results: Heparin treatment did not influence cell viability, and no influence of heparins in combination with paclitaxel was seen for the evaluated cancer cell lines HEC-1-A, KLE, RL 95-2 and AN3-CA compared to untreated cells. Secretion of the cytokines CCL5, CCL2 and IL-6 increased after paclitaxel treatment in several endometrial cancer cell lines, but no general effect on cytokine secretion was detected after heparin treatment. A significant decrease in CCL5 expression was only detected in KLE cells following treatment with heparin and paclitaxel, and an increase in the expression of CCL5 in RL 95-2 cells. Conclusion: Further in-depth studies are needed to investigate the functions of cytokines CCL2, CCL5 and IL-6 in endometrial cancer cells treated with paclitaxel. Although no general effect on cytokine secretion was detected following heparin treatment, a selective modulatory impact could exist.

11.
Infect Agent Cancer ; 12: 30, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28572836

RESUMO

BACKGROUND: Though TRAIL has been hailed as a promising drug for tumour treatment, it has been observed that many tumour cells have developed escape mechanisms against TRAIL-induced apoptosis. As a receptor of LPS, TLR 4, which is expressed on a variety of cancer cells, can be associated with TRAIL-resistance of tumour cells and tumour progression as well as with the generation of an anti-tumour immune response. METHODS: In this study, the sensitivity to TRAIL-induced apoptosis as well as the influence of LPS-co-stimulation on the cell viability of the pancreatic cancer cell lines PANC-1, BxPC-3 and COLO 357 was examined by FACS analyses and a cell viability assay. Subsequently, the expression of TRAIL-receptors was detected via FACS analyses. Levels of osteoprotegerin (OPG) were also determined using an enzyme-linked immunosorbent assay. RESULTS: PANC-1 cells were shown to be resistant to TRAIL-induced apoptosis. This was accompanied by significantly increased osteoprotegerin levels and a significantly decreased expression of DR4. In contrast, TRAIL significantly induced apoptosis in COLO 357 cells and to a lesser degree in BxPC-3 cells. Co-stimulation of COLO 357 as well as BxPC-3 cells combining TRAIL and LPS resulted in a significant decrease in TRAIL-induced apoptosis. In COLO 357 cells TRAIL-stimulation decreased the levels of OPG thereby not altering the expression of the TRAIL-receptors 1-4 resulting in a high susceptibility to TRAIL-induced apoptosis. Co-stimulation with LPS and TRAIL completely reversed the effect of TRAIL on OPG levels reaching a 2-fold increase beyond the level of non-stimulated cells resulting in a lower susceptibility to apoptosis. In BxPC-3, TRAIL stimulation decreased the expression of DR4 and significantly increased the decoy receptors TRAIL-R3 and TRAIL-R4 leading to a decrease in TRAIL-induced apoptosis. OPG levels remained unchanged. Co-stimulation with TRAIL and LPS further enhanced the changes in TRAIL-receptor-expression promoting apoptosis resistance. CONCLUSIONS: Here it has been shown that TRAIL-resistance in pancreatic cancer cells can be mediated by the inflammatory molecule LPS as well as by different expression patterns of functional and non-functional TRAIL-receptors.

12.
Oncol Lett ; 13(4): 2847-2851, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28454476

RESUMO

PARP inhibitors are used in the treatment of gynecological malignancies and it has been demonstrated in preclinical studies that PARP inhibition sensitizes cancer cells to cytotoxic agents. In the present study, PARP expression was detected in different endometrial cancer cell lines by western blot analysis, and PARP activity was measured using an enzymatic assay. In addition, the endometrial cancer cell lines were treated with paclitaxel or carboplatin in combination with the PARP inhibitor PJ34 prior to a cell viability assay and apoptotic nuclei measurement. PARP protein was detected in all four cell lines examined, although its activity varied between the cell lines. Treatment with PJ34 in combination with paclitaxel decreased endometrial cancer cell viability compared with treatment with paclitaxel alone. These results indicate that the inhibition of PARP with PJ34 sensitizes endometrial cancer cells to cytotoxic treatment with paclitaxel.

13.
PLoS One ; 11(12): e0167386, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27907089

RESUMO

INTRODUCTION: Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions. PATIENTS AND METHODS: 67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System). RESULTS: All 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn't be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred. CONCLUSION: HPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past medical history seemed to be significant factors for early relapse.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias Vaginais/diagnóstico , Adulto , Idoso , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Vagina/patologia , Vagina/virologia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/virologia
14.
Am J Reprod Immunol ; 76(5): 415-425, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27650411

RESUMO

PROBLEM: Recent studies revealed appropriate differentiation of recent thymic emigrant (RTE)-regulatory T cells (Tregs) to be crucial for maintaining healthy pregnancy. Currently, the role of responder T cells (Tresps) is not known. METHOD OF STUDY: Six-color flow cytometric analysis was used to detect differences in the differentiation of highly proliferative inducible co-stimulatory (ICOS)+ -RTE-Tregs/Tresps and apoptosis-sensitive ICOS- -RTE-Tregs/Tresps into mature naïve (MN)-, CD31+ -memory and CD31- -memory Tregs/Tresps in women with spontaneous preterm labor (sPL) compared to healthy pregnancy. RESULTS: Healthy pregnancy was characterized by an increased differentiation of ICOS+ - and ICOS- -RTE-Tregs, as well as ICOS+ -RTE-Tresps via CD31+ -memory Tregs/Tresps into CD31- -memory Tregs/Tresps. Women with sPL showed an early interruption of RTE-Treg/Tresp differentiation. Instead, ICOS+ -MN-Tresps and partly ICOS- -MN-Tregs differentiated into CD31- -memory Tregs/Tresps, causing a significant reduction of both ICOS+ -Tregs and ICOS+ -Tresps, but an increase of ICOS- -Tresps within total CD4+ -T-helper cells. CONCLUSION: Aberrant differentiation of ICOS+ -T cells is associated with sPL.


Assuntos
Trabalho de Parto Prematuro/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Timo/imunologia , Adulto , Diferenciação Celular , Separação Celular , Células Cultivadas , Feminino , Citometria de Fluxo , Humanos , Tolerância Imunológica , Memória Imunológica , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Ativação Linfocitária , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Gravidez , Adulto Jovem
15.
Anticancer Res ; 36(4): 1535-44, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27069129

RESUMO

BACKGROUND/AIM: This in vitro study analyzed the impact of heparins on expression of chemokines in human endometrial adenocarcinoma cell lines. MATERIALS AND METHODS: Cell lines were incubated with unfractionated heparin (UFH), low molecular weight heparins (LMWH) and fondparinux under hypoxic and normoxic conditions. Chemokine (C-X-C motif) ligand 8 (CXCL8), CC-chemokine ligand 2 (CCL2) and CCL5 were detected by enzyme-linked immunosorbent assays and real-time reverse transcriptase-polymerase chain reaction and cell viability by fluorometric assay. RESULTS: Different adenocarcinoma cell lines had distinct patterns of chemokine expression. UFH attenuated the secretion of CXCL8 and CCL2, and enhanced that of CCL5. The observed effects of heparin were in addition to the anti-coagulatory properties of heparin and dependent on molecular size and charge. CONCLUSION: UFH has selective modulating effects on the secretion of CXCL8, CCL2 and CCL5 in different endometrial adenocarcinoma cell lines. Molecular size and charge are relevant for these observed effects. By influencing the expression of these inflammatory mediators and thereby affecting the tumour microenvironment, heparins and related agents might play an essential role in the development of new therapeutic strategies.


Assuntos
Adenocarcinoma/metabolismo , Quimiocina CCL2 , Quimiocina CCL5 , Neoplasias do Endométrio/metabolismo , Heparina/farmacologia , Interleucina-8 , Linhagem Celular Tumoral , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Feminino , Fondaparinux , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Polissacarídeos/farmacologia
16.
J Assist Reprod Genet ; 33(7): 949-57, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27011369

RESUMO

PURPOSE: The aim of this paper is to study the impact of heparin on the response of human endometrial stromal cells (ESCs) to interleukin (IL)-1ß during decidualization in vitro. METHODS: ESCs were isolated from hysterectomy specimens of premenopausal women undergoing hysterectomy for benign reasons; decidualized in vitro and incubated in parallel with unfractionated heparin or tinzaparin; and stimulated with IL-1ß at days 0, 3, 6, and 9 during decidualization. IL-6, IL-11, and leukemia inhibitory factor (LIF) were analyzed using ELISAs and real-time RT-PCR. Cell viability was determined by a fluorometric assay. RESULTS: IL-1ß dose-dependently stimulated IL-6, IL-11, and LIF in distinct patterns in ESCs during decidualization. Unfractionated heparin as well as tinzaparin attenuated the IL-1ß-mediated induction of IL-6, IL-11, and LIF on protein and messenger RNA (mRNA) levels. The relative effects of heparin and tinzaparin were getting more pronounced during the time course of decidualization. CONCLUSIONS: Unfractionated heparin and the low molecular weight heparin tinzaparin have modulating effects on IL-1ß-induced endometrial cytokines of the IL-6 family during decidualization. These effects of heparins beyond their classical anti-coagulatory properties might have implications on the regulation of endometrial receptivity and early implantation.


Assuntos
Decídua/embriologia , Endométrio/citologia , Heparina de Baixo Peso Molecular/farmacologia , Heparina/farmacologia , Interleucina-11/metabolismo , Interleucina-6/metabolismo , Fator Inibidor de Leucemia/metabolismo , Sobrevivência Celular , Implantação do Embrião , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Histerectomia , Interleucina-1beta/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Tinzaparina
17.
Arch Gynecol Obstet ; 294(3): 455-66, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26711837

RESUMO

PURPOSE: This study aimed to investigate socio-demographic, medical and psychological factors that have an impact on breastfeeding. METHODS: Questionnaires were administered to 330 women prenatally (TI third trimester) and postpartum (TII 3-4 days, TIII 4 months). Medical data were collected from the hospital records. Self-reported data on initiation and maintenance of breastfeeding was collected simultaneously. Primary endpoint was breastfeeding initiation and maintenance. Data analyses were performed using Spearman's ρ correlations between breastfeeding and other study variables and generalized multiple ordinal logistic regression analysis. RESULTS: Neonatal admission to the NICU, high BMI, cesarean section, difficulties with breastfeeding initiation and high maternal state anxiety were the strongest predictors of impaired breastfeeding initiation, explaining together 50 % of variance. After 4 months, the strongest predictors of impaired maintenance of breastfeeding were maternal smoking, a high BMI and a history of postpartum anxiety disorder, explaining 30 % of variance. CONCLUSIONS: Successful initiation and maintenance of breast feeding is a multifactorial process. Our results underline the need of interdisciplinary approaches to optimise breastfeeding outcomes by demonstrating the equality of medical and psychological variables. Whereas practices on maternity wards are crucial for optimal initiation, continuous lifestyle modifying and supporting approaches are essential for breastfeeding maintenance. Healthcare providers can also significantly influence breastfeeding initiation and maintenance by counselling on the importance of maternal BMI.


Assuntos
Aleitamento Materno , Adulto , Transtornos de Ansiedade/psicologia , Índice de Massa Corporal , Aleitamento Materno/psicologia , Feminino , Humanos , Modelos Logísticos , Gravidez , Inquéritos e Questionários
18.
Reprod Biol ; 15(3): 146-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26370457

RESUMO

The pro-inflammatory T helper (Th)-1 cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are immunological factors relevant at the feto-maternal interface and involved in the pathophysiology of implantation disorders. The synergistic action of the two cytokines has been described with regard to apoptotic cell death and inflammatory responses in different cell types, but little is known regarding the human endometrium. Therefore, we examined the interaction of TNF-α and IFN-γ in human endometrial stromal cells (ESCs). ESCs were isolated from specimens obtained during hysterectomy and decidualized in vitro. Cells were incubated with TNF-α, IFN-γ or signaling-inhibitor. Insulin-like growth factor binding protein (IGFBP)-1, prolactin (PRL), leukemia inhibitory factor (LIF), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted protein (RANTES) and monocyte chemotactic protein (MCP)-1 were measured using ELISA and real-time RT-PCR. Nuclear factor of transcription (NF)-κB and its inhibitor (IκBα) were analyzed by in-cell western assay and transcription factor assay. TNF-α inhibited and IFN-γ did not affect the decidualization of ESCs. In contrast, IFN-gamma differentially modulated the stimulating effect of TNF-alpha on cytokines by enhancing IL-6, RANTES and MCP-1 and attenuating LIF mRNA expression. These effects were time- and dose-dependent. IFN-γ had no impact on the initial activation of NF-κB signaling. Histone-deacetylase activity was involved in the modulating effect of IFN-γ on RANTES secretion. These observations showed a distinct pattern of interaction of the Th-1 cytokines, TNF-α and IFN-γ in the human endometrium, which could play an important role in the pathophysiology of implantation disorders.


Assuntos
Endométrio/efeitos dos fármacos , Interferon gama/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Apoptose/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Endométrio/citologia , Endométrio/metabolismo , Feminino , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Fator Inibidor de Leucemia/metabolismo , Prolactina/metabolismo , Células Estromais/citologia , Células Estromais/metabolismo
19.
PLoS One ; 10(6): e0129104, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26121653

RESUMO

OBJECTIVE: Emergency cervical cerclage is one of the treatment options for the reduction of preterm birth. The aim of this study is to assess neonatal outcome after cerclage with special focus on adverse effects in very low birth weight infants. STUDY DESIGN: Retrospective cohort study. Classification of cerclages in history-indicated (HIC, n = 38), ultrasound-indicated (UIC, n = 29) and emergency/ physical examination-indicated (PEIC, n = 33) cerclage. Descriptive analysis of pregnancy and neonatal outcome (admission to NICU, duration of hospitalization, respiratory outcome (intubation, CPAP, FiO2max), neonatal complications (ROP, IVH)). Statistical comparison of perinatal parameters and outcome of neonates <1500 g after cerclage with a birth weight matched control group. RESULTS: Neonates <1500 g after PEIC show significantly impaired outcome, i.e. prolonged respiratory support (total ventilation in days, CPAP, FiO2max) and higher rates of neonatal complications (IVH ≥ II, ROP ≥ 2). Placental pathologic evaluation revealed a significantly higher rate of chorioamnionitis (CAM) after PEIC. Neonates <1500 g after UIC or HIC show no significant difference in neonatal complications or CAM. CONCLUSIONS: In our study PEIC is associated with adverse neonatal outcome in infants <1500 g. The high incidence of CAM indicates a potential inflammatory factor in the pathogenesis. Large well-designed RCTs are required to give conclusive answers to the question whether to prolong or to deliver.


Assuntos
Cerclagem Cervical , Tratamento de Emergência , Resultado da Gravidez , Adulto , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Gravidez
20.
Immunol Cell Biol ; 93(10): 858-67, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25915117

RESUMO

During pregnancy, regulatory T cells (Tregs) have a key role in maternal immune tolerance to the semi-allogeneic fetus. Our previous results showed that the naive CD45RA(+)-Treg pool is functionally improved in pregnant women compared with non-pregnant women. Therefore, we examined the thymic output and differentiation of CD45RA(+)CD31(+) recent thymic emigrant (RTE)-Tregs during normal pregnancy and in the presence of preeclampsia. With the onset of pregnancy, the composition of the total CD4(+)CD127(low+/-)FoxP3(+)-Treg pool changed in the way that its percentage of RTE- and CD45RA(-)CD31(+)-memory Tregs decreased strongly, whereas that of the CD45RA(+)CD31(-)-mature naive (MN)-Tregs did not change and that of the CD45RA(-)CD31(-)-memory Tregs increased complementary. Thereby, the ratio of RTE-/MN-Tregs decreased from 1.0 to 0.7 leading to a significant increase in the suppressive activity of the naive CD45RA(+)-Treg pool. This effect was confirmed by re-assembling separated RTE- and MN-Tregs from non-pregnant women in the ratio of pregnant women. The suppressive activity of both separated naive Treg subsets was equally high in non-pregnant and pregnant women, but considerably reduced in preeclampsia patients, who showed significantly increased percentages of CD45RA(-)CD31(+)-memory Tregs, but decreased percentages of RTE- and MN-Tregs. Our results suggest a reduced thymic output of RTE-Tregs during pregnancy, which causes a decrease in the ratio of RTE-/MN-Tregs and thus an increase in the differentiation of RTE-Tregs towards CD45RA(-)CD31(-)-memory Tregs. Presumably, this differentiation of RTE-Tregs, which was impaired in preeclampsia patients, ensures the improved suppressive activity of the CD45RA(+)-naive Treg pool and thus retains the maintenance of pregnancy.


Assuntos
Pré-Eclâmpsia/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Timo/imunologia , Adolescente , Adulto , Animais , Diferenciação Celular , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Tolerância Imunológica , Memória Imunológica , Antígenos Comuns de Leucócito/metabolismo , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
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