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1.
J Reprod Immunol ; 138: 103098, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32045760

RESUMO

The present review article compares NK cell subsets and cytokine patterns determined in the peripheral blood as well as results of functional in-vitro assays using peripheral NK cells of idiopathic recurrent miscarriage (iRM) patients with corresponding results obtained in female healthy controls and female renal transplant recipients with good long-term graft function. Immune mechanisms, inducing transplant rejection in long-term transplant recipients might also be able to induce rejection of semi-allogeneic fetal cells in patients with iRM. Consequently, the immune status of transplant recipients with good stable long-term graft function should be different from the immune status of iRM patients. iRM patients show a strong persistent cytotoxic NK cell response in the periphery. Simultaneously, immunostimulatory Th1 as well as immunosuppressive Th2 type lymphocytes in the blood are strongly activated but plasma levels of immunosuppressive Th2 type cytokines are abnormally low. In-vitro, unstimulated NK cell cultures of iRM patients show a strong spontaneous TGF-ß1 release in the supernatant but lower TGF-ß1 levels after stimulation with tumor cell line K562, suggesting strong consumption of TGF-ß1 by pre-activated NK cells of iRM patients that might contribute to the low systemic Th2 type plasma levels. iRM patients do not show a systemic switch to a Th2 type cytokine pattern and one might hypothesize that low TGF-ß plasma levels indicate low TGF-ß levels in the micromilieu immediately before fetal rejection. Persistent TGF-ß deficiency implies a persistent unfavorable micromilieu for pregnancy resulting in failing tolerance induction due to lack of TGF-ß, a condition that might contribute to iRM.

2.
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
3.
Geburtshilfe Frauenheilkd ; 79(11): 1171-1175, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31736505

RESUMO

This position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth.

4.
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
5.
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.

6.
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.

7.
Geburtshilfe Frauenheilkd ; 79(8): 834-843, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423018

RESUMO

Numerous experimental studies indicate that natural progesterone, through various mechanisms, exerts an inhibitory effect on uterine contractility and sensitises the myometrium for tocolytics. It was therefore appropriate to investigate the possible benefits of oral/vaginal progesterone and the synthetic progesterone derivative 17-α-hydroxyprogesterone caproate, applied intramuscularly, in clinical studies on primary tocolysis, additively to established tocolytics ("adjunctive tocolysis") and as maintenance treatment after successful tocolysis in cases of threatened preterm birth. Three studies with a small number of cases do not yield any sufficient evidence for recommending progesterone/17-α-hydroxyprogesterone caproate as primary tocolysis in women with preterm labour. There is also no evidence that progesterone or 17-α-hydroxyprogesterone caproate combined with commonly used tocolytics leads to a prolongation of pregnancy and a significant decrease in the rate of preterm birth. The data on the use of progesterone as maintenance treatment is controversial. While randomised, controlled studies with low quality showed promising results, studies with high quality did not reveal any significant differences with regard to the rate of preterm birth < 37 weeks of gestation, the latency period until delivery and in the neonatal outcome between progesterone/17-α-hydroxyprogesterone caproate and placebo or no treatment. Significant differences in the methodology, the inclusion and outcome criteria, the mode of application and the dosages of the substances as well as the inadequate statistical power as a result of low numbers of cases make interpretation and comparability of the studies difficult. Therefore, well-designed randomised, placebo-controlled, double-blind studies with uniform primary outcome criteria are needed in order to clarify whether progesterone and via which route of administration and at which dosage is of clinical benefit for patients with manifest preterm contractions and as maintenance treatment after arrested preterm labour.

8.
Geburtshilfe Frauenheilkd ; 79(8): 844-853, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423019

RESUMO

The prevention and treatment of preterm birth remains one of the biggest challenges in obstetrics. Worldwide, 11% of all children are born prematurely with far-reaching consequences for the children concerned, their families and the health system. Experimental studies suggest that progesterone inhibits uterine contractions, stabilises the cervix and has immunomodulatory effects. Recent years have seen the publication of numerous clinical trials using progestogens for the prevention of preterm birth. As a result of different inclusion criteria and the use of different progestogens and their methods of administration, it is difficult to draw comparisons between these studies. A critical evaluation of the available studies was therefore carried out on the basis of a search of the literature (1956 to 09/2018). Taking into account the most recent randomised, controlled studies, the following evidence-based recommendations emerge: In asymptomatic women with singleton pregnancies and a short cervical length on ultrasound of ≤ 25 mm before 24 weeks of gestation (WG), daily administration of vaginal progesterone (200 mg capsule or 90 mg gel) up until 36 + 6 WG leads to a significant reduction in the preterm birth rate and an improvement in neonatal outcome. The latest data also suggest positive effects of treatment with progesterone in cases of twin pregnancies with a short cervical length on ultrasound of ≤ 25 mm before 24 WG. The study data for the administration of progesterone in women with singleton pregnancies with a previous preterm birth have become much more heterogeneous, however. It is not possible to make a general recommendation for this indication at present, and decisions must therefore be made on a case-by-case basis. Even if progesterone use is considered to be safe in terms of possible long-term consequences, exposure should be avoided where it is not indicated. Careful patient selection is crucial for the success of treatment.

9.
BMC Immunol ; 20(1): 10, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832584

RESUMO

BACKGROUND: Previously, we demonstrated up-regulated activated CD4+ and CD8+ T lymphocytes as well as up-regulated cytotoxic NK cells in the blood of patients with idiopathic recurrent miscarriage. In the present study, we tried to identify deficiencies in counter-regulating immune mechanisms of these patients. METHOD: Cytokines were determined in NK cells and in plasma samples of 35 healthy controls, 33 patients with idiopathic recurrent miscarriage, 34 patients with end stage renal disease, 10 transplant patients early and 37 transplant patients late post-transplant using flow-cytometry and luminex. In addition, cytokines were studied in supernatants of cell cultures with peripheral blood mononuclear cells stimulated in-vitro with tumor cell line K562. RESULTS: Patients with idiopathic recurrent miscarriage exhibited the highest absolute cell counts of circulating TGFß1+ NK, NKT and T lymphocytes and the lowest TGFß1 plasma levels of all study groups (for all p < 0.050). In-vitro, peripheral blood mononuclear cells of patients with idiopathic recurrent miscarriage showed high spontaneous TGFß1 production that could not be further increased by stimulation with K562, indicating increased consumption of TGFß1 by activated cells in the cell culture. Moreover, patients with idiopathic recurrent miscarriage had abnormally high IL4+ as well as abnormally high IFNy+ NK cells (p < 0.010) but similar IL10+ NK cell numbers as female healthy controls and showed the lowest plasma levels of IL10, TGFß3, IL1RA, IL1ß, IL5, IL6, IL8, IL17, TNFα, GM-CSF, TPO and VEGF and the highest plasma levels of G-CSF, FGF-basic, CCL3 and CXCL5 as compared to female HC and female transplant recipients (for all p < 0.050). CONCLUSIONS: Patients with idiopathic recurrent miscarriage show an activated immune system that can hardly be stimulated further and cannot be efficiently down-regulated by up-regulated TGFß1+ and IL4+ NK, NKT and T lymphocytes which are present concomitantly in these patients. The strongly decreased TGFß and IL10 plasma levels indicate deficient down-regulation and reflect a dysbalance of the immune system in patients with idiopathic recurrent miscarriage. These findings may be relevant for explaining the pathogenesis of idiopathic recurrent miscarriage.


Assuntos
Aborto Habitual/sangue , Aborto Habitual/imunologia , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Células T Matadoras Naturais/imunologia , Subpopulações de Linfócitos T/imunologia , Fator de Crescimento Transformador beta/sangue , Biomarcadores , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Células T Matadoras Naturais/metabolismo , Receptores de Citocinas/metabolismo , Subpopulações de Linfócitos T/metabolismo
10.
Dtsch Arztebl Int ; 116(50): 858-864, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931955

RESUMO

BACKGROUND: The preterm birth rate in Germany has remained unchanged at 8-9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care. METHODS: This review is based on pertinent publications from the years 2000-2019 that were retrieved by a selective search in PubMed. RESULTS: The clinical risk factors for preterm birth-known mainly from retrospective cohort studies-include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e., <25 mm in the second trimester (aOR: 6.9). In women with a short cervix, vaginally administered progesterone significantly lowers the preterm birth rate (22.5% vs. 14.1% for birth before 33 weeks of gestation, RR: 0.62; 95% confidence interval [0.47; 0.81]). Nicotine abstinence is associated with a lower pre- term birth rate as well (aOR: 0.91; [0.88; 0,.94]), while working more than 40 hours per week (aOR: 1.25; [1,.01; 1,.54]) and heavy lifting during pregnancy (hazard ratio [HR]: 1.43; [1.13; 1.80]) are associated with a higher preterm birth rate. Avoidance of physical exertion, or bed rest, in the face of impending preterm birth does not lower the preterm birth rate, but it does increase the risk of complications, such as thromboembolism. CONCLUSION: The meticulous assessment and elimination of treatable risk factors at the outset of ambulatory prenatal care can help lower the preterm birth rate. Further velopment of causally directed treat- ments (e.g., changes of relevant environmental and epigenetic factors).

11.
Pediatr Res ; 84(5): 757-764, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30135596

RESUMO

BACKGROUND: A pro-inflammatory intrauterine milieu accounts for increased perinatal morbidity and mortality. We asked how maternal inflammation as seen in endotoxemia affects fetal leukocyte recruitment in vivo during late gestation. METHODS: Inflammation was induced in pregnant LysEGFP-mice by intraperitoneal LPS injection between gestational day 14 and 18 (E14-E18). After 20 h, intravital fluorescence microscopy was performed on fetal yolk sac venules to examine leukocyte rolling (number of rolling cells/min) and adhesion (>30 s). Infiltration of neutrophils into chorion/amnion, lung, and kidney were quantified by immunofluorescence microscopy. RESULTS: At high doses (2 × 1 mg/kg), LPS triggered preterm birth (PTB) and intrauterine fetal death (IUFD), with early gestations at high risk of IUFD and late gestations prone to PTB. Lower LPS dosing (2 × 0.25 mg/kg) did not induce labor, but promoted maternal and fetal cytokine production, as well as neutrophilic infiltration of fetal membranes, as seen in chorioamnionitis (CAM). Baseline fetal leukocyte recruitment increased throughout gestation, and maternal inflammation further augmented adhesion at E16-E18. Enhanced leukocyte recruitment ultimately translated into prominent infiltration of fetal lung and kidney. CONCLUSION: LPS-induced maternal endotoxemia promotes IUFD, PTB, and fetal leukocyte recruitment depending on gestational age. Our proposed model may serve as a platform to test novel perinatal immune modulators.


Assuntos
Feto/citologia , Inflamação/patologia , Leucócitos/patologia , Lipopolissacarídeos/farmacologia , Âmnio/patologia , Animais , Córion/patologia , Feminino , Proteínas de Fluorescência Verde/genética , Inflamação/induzido quimicamente , Masculino , Troca Materno-Fetal , Camundongos , Camundongos Endogâmicos C57BL , Gravidez
12.
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
13.
Geburtshilfe Frauenheilkd ; 78(4): 364-381, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29720743

RESUMO

Purpose: Official guideline of the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (ÖGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). The aim of this guideline was to standardize the diagnosis and treatment of couples with recurrent miscarriage (RM). Recommendations were based on the current literature and the views of the involved committee members. Methods: Based on the current literature, the committee members developed the statements and recommendations of this guideline in a formalized process which included DELPHI rounds and a formal consensus meeting. Recommendations: Recommendations for the diagnosis and treatment of patients with RM were compiled based on the international literature. Specific established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders were taken into consideration.

14.
Transpl Immunol ; 49: 59-71, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29702201

RESUMO

BACKGROUND: There is evidence that NK cells with low cytotoxicity but strong immunoregulatory characteristics contribute to good graft outcome. We attempted to investigate which NK cell subsets increase post-transplant and might affect graft function. METHOD: Lymphocyte and NK cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients pre-transplant and post-transplant. In total, 31 transplant recipients were studied. RESULTS: When cell numbers were compared in 9 patients pre- and 6 months post-transplant, post-transplant CD56dimCD16+ (p = 0.011) NK cells with the phenotype CD158a+ (p = 0.008), CD158e+ (p = 0.038), NKG2A+ (p = 0.008), NKG2D+ (p = 0.011), IFNyR+ (p = 0.008), perforin+ (p = 0.008), granzymeB+ (p = 0.008), perforin+granzymeB+ (p = 0.008) and perforin-granzymeB- (p = 0.021) were lower than those pre-transplant, indicating a post-transplant reduction of cytotoxic NK cells. In 28 patients NK cell subsets were analyzed with respect to time post-transplant (median 888 days post-transplant). CD56dimCD16+ NK cells co-expressing CD158a (p = 0.014), NKG2D (p = 0.047), IL4R (p = 0.038), IL10R (p = 0.008) and IFNy (p = 0.036) as well as CD56bright NK cells with the phenotype TGFß+ (p = 0.017), TGFR+ (p = 0.035), CD158a+ (p = 0.042) and perforin-granzymeB- (p = 0.048) increased with time post-transplant. CONCLUSION: Post-transplant, cytotoxic NK cells were lower than pre-transplant and remained low, whereas NK cell subsets with potentially immunoregulatory properties increased.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Complicações Pós-Operatórias/imunologia , Adulto , Idoso , Separação Celular , Citotoxicidade Imunológica , Feminino , Citometria de Fluxo , Humanos , Imunomodulação , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
15.
Arch Gynecol Obstet ; 297(5): 1157-1167, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29404742

RESUMO

OBJECTIVES: In understanding early disturbances in the mother-child relationship, maternal-fetal attachment has become an important concept. To date no study has investigated the reliability and validity of the German version of the Maternal Fetal Attachment Scale (MFAS). The present study aimed to close this gap. METHODS: Questionnaires were completed in a sample of 324 women [third trimester (T1), first week postpartum (T2), and 4 months postpartum (T3)]. In addition to the MFAS (T1), the following measures were assessed: the questionnaire of partnership (T1), the postpartum bonding questionnaire (T2), the Edinburgh Postnatal Depression Scale (T1-T3), the State Trait Anxiety Inventory (T1-T3), and the pregnancy related anxiety questionnaire (T1-T3). Factor structure was analyzed using a principal component analysis (PCA) with varimax rotation. Internal and convergent validities were calculated. RESULTS: In contrast to the original version with five subscales, PCA yielded a three-factor solution, consisting of the three independent dimensions "anticipation", "empathy", and "caring", explaining 34.9% of the variance together. Good internal reliabilities were found for the total MFAS scale. Maternal-fetal attachment showed a significant negative correlation with postpartum bonding impairment. While no correlations were found with depression, general anxiety and pregnancy-related anxiety during pregnancy, maternal-fetal attachment was significantly related to aspects of partnership quality. In the postpartum period, maternal attachment showed a strong negative correlation with maternal anxiety. CONCLUSIONS: Our results suggest that the German version of the MFAS is a reliable and valid questionnaire to measure the emotional relationship of the mother to the unborn child during pregnancy.


Assuntos
Depressão Pós-Parto/diagnóstico , Relações Materno-Fetais , Mães/psicologia , Apego ao Objeto , Gestantes/psicologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Inquéritos e Questionários/normas , Adulto , Ansiedade/complicações , Ansiedade/diagnóstico , Ansiedade/psicologia , Depressão/complicações , Depressão/diagnóstico , Depressão/psicologia , Depressão Pós-Parto/complicações , Depressão Pós-Parto/psicologia , Feminino , Alemanha , Humanos , Inventário de Personalidade , Período Pós-Parto , Gravidez , Terceiro Trimestre da Gravidez , Psicometria , Reprodutibilidade dos Testes
16.
PLoS One ; 12(10): e0186349, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29040297

RESUMO

BACKGROUND: There is evidence that NK-cell reactivity might affect graft outcome in transplant recipients and pregnancy in women. METHOD: NK-cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients before and after renal transplantation, patients with recurrent miscarriage (RM) and healthy controls (HC). RESULTS: Patients late post-transplant (late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0.021) whereas RM patients exhibited abnormally high numbers of these cells (vs HC p = 0.043). CD56dimCD16+perforin+granzyme+ NK-cell counts were strikingly different between the two patient groups (p<0.001). In addition, recipients late-Tx showed abnormally low CD8+ NK-cells (vs HC p<0.001) in contrast to RM patients who showed an abnormal increase (vs HC p = 0.008). CD8+ NK-cell counts were strongly different between the two patient groups (p<0.001). Higher perforin+granzyme+CD56dimCD16+ and CD8+ NK-cells were associated with impaired graft function (p = 0.044, p = 0.032). After in-vitro stimulation, CD56dimCD16+ and CD56brightCD16dim/- NK-cells showed strong upregulation of CD107a and IFNy, whereas the content of perforin decreased dramatically as a consequence of perforin release. Recipients late post-Tx showed less in-vitro perforin release (= less cytotoxicity) than HC (p = 0.037) and lower perforin release was associated with good graft function (r = 0.738, p = 0.037). Notably, we observed strong in-vitro perforin release in 2 of 6 investigated RM patients. When circulating IL10+CD56bright NK-cells were analyzed, female recipients late post-Tx (n = 9) showed significantly higher relative and absolute cell numbers than RM patients (p = 0.002 and p = 0.018, respectively); and high relative and absolute IL10+CD56bright NK-cell numbers in transplant recipients were associated with low serum creatinine (p = 0.004 and p = 0.012) and high glomerular filtration rate (p = 0.011 and p = 0.002, respectively). Female recipients late post-Tx exhibited similar absolute but higher relative numbers of IL10+IFNy- NK-cells than RM patients (p>0.05 and p = 0.016, respectively). CONCLUSION: NK-cells with lower cytotoxicity and immunoregulatory function might contribute to good long-term graft outcome, whereas circulating NK-cells with normal or even increased cytotoxicity and less immunoregulatory capacity are observed in patients with RM.


Assuntos
Aborto Habitual/sangue , Transplante de Rim/efeitos adversos , Rim/imunologia , Células Matadoras Naturais/imunologia , Aborto Habitual/imunologia , Aborto Habitual/patologia , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , Feminino , Citometria de Fluxo , Taxa de Filtração Glomerular , Granzimas/sangue , Humanos , Rim/metabolismo , Rim/patologia , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Perforina/sangue , Gravidez , Transplantados
17.
Transpl Immunol ; 43-44: 3-10, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28757397

RESUMO

BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study. The absolute counts of CD4+ and CD8+ T, CD16+ CD56+ NK, CD19+ B, CD4+ CD25+ CD127- Foxp3+ (Tregs), Helios+ Tregs, CD38+ Tregs, and CD4+ CD17+ (Th17) cells were analyzed in peripheral blood in both patient groups. In addition, serum 25 (OH) D3, 1, 25 (OH)2 D3, IL-6, IL-17, IL-23, and TGF-ß1 were measured. The association between lymphocyte subset counts and 1, 25 (OH)2 D3 or 25 (OH) D3 was studied, as was the association between serum IL-6, IL-17, IL-23, or TGF-ß1 and 1,25 (OH)2 D3 or 25 (OH) D3. RESULTS: Serum 25 (OH) D3 and 1,25 (OH)2 D3 levels were not independently associated with peripheral CD4+ T, CD19+ B, CD16+ CD56+ NK, Treg, or Th17 cell counts. In contrast to serum 25 (OH) D3, serum1, 25 (OH)2 D3 was positively associated with CD8+ T cells counts in renal transplant recipients. CONCLUSION: Our findings indicate low utility of serum 25 (OH) D3 and 1, 25 (OH)2 D3 levels in predicting a change in lymphocyte subset counts in ESRD and renal transplant patients.


Assuntos
Calcifediol/sangue , Calcitriol/sangue , Falência Renal Crônica/sangue , Transplante de Rim , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Adulto , Contagem de Linfócito CD4 , Calcifediol/imunologia , Calcitriol/imunologia , Citocinas/imunologia , Feminino , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia
18.
Eur J Obstet Gynecol Reprod Biol ; 216: 164-168, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28777967

RESUMO

OBJECTIVES: Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone. STUDY DESIGN: Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve® (also known as Crinone®), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied. RESULTS: Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P<0.05-<0.001) delay delivery, but vaginal Prochieve® did not. Administration of P4 in late gestation also prevented (P<0.001) delivery even when given 8h before delivery. CONCLUSIONS: Prochieve® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration.


Assuntos
Hidroxiprogesteronas/uso terapêutico , Nascimento Prematuro/prevenção & controle , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Caproato de 17 alfa-Hidroxiprogesterona , Administração Cutânea , Administração Retal , Animais , Esquema de Medicação , Portadores de Fármacos , Feminino , Hidroxiprogesteronas/administração & dosagem , Injeções Subcutâneas , Gravidez , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Ratos , Resultado do Tratamento
19.
Am J Reprod Immunol ; 78(4)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28639334

RESUMO

PROBLEM: Uterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls. METHOD OF STUDY: Out of n=130 couples with ≥3 consecutive, clinical RM screened according to a standardized diagnostic protocol, n=58 patients with iRM were identified. Endometrial biopsies were investigated in patients and n=17 fertile women (controls) via immunohistochemistry. RESULTS: Compared to controls, the concentration of uNK cells was significantly higher in iRM patients (257±212 vs. 148±73 uNK cells/mm², P=.04). IRM patients showed a higher prevalence of >300 uNK cells/mm² than controls (34.5% vs. 5.9%, P=.02). In 88% of controls and 62% of iRM patients, uNK cells were detected within the range of 40-300/mm². CONCLUSION: Idiopathic recurrent miscarriage patients showed higher uNK cell levels than controls supporting the possible impact of uNK cells in the pathophysiology of miscarriage. Our cutoff levels might help to select RM patients which may benefit from immunomodulatory treatment.


Assuntos
Aborto Habitual/imunologia , Endométrio/patologia , Células Matadoras Naturais/imunologia , Útero/patologia , Adulto , Biópsia , Movimento Celular , Implantação do Embrião , Endométrio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Contagem de Linfócitos , Gravidez
20.
Arch Gynecol Obstet ; 295(4): 873-883, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28251311

RESUMO

PURPOSE: Reduced sexual activity and dysfunctional problems are highly prevalent in the perinatal period, and there is a lack of data regarding the degree of normality during pregnancy. Several risk factors have been independently associated with a greater extent of Female Sexual Dysfunction (FSD). Therefore, this study aimed to assess the prevalence of sexual inactivity and sexual dysfunctions in German women during the perinatal period and the verification of potential risk factors. METHODS: Questionnaires were administered to 315 women prenatally (TI 3rd trimester) and postpartum (TII 1 week, TIII 4 months), including the Female Sexual Function Index (FSFI), the Edinburgh Postnatal Depression Scale (EPDS), and the Questionnaire of Partnership (PFB). RESULTS: The frequency of sexual inactivity was 24% (TI), 40.5% (TII), and 19.9% (TIII). Overall, 26.5-34.8% of women were at risk of sexual dysfunction (FSFI score <26.55) at all measurement points. Sexual desire disorder was the most prevalent form of Female sexual dysfunction. Furthermore, especially breastfeeding and low partnership quality were revealed as significant risk factors for sexual dysfunctional problems postpartum. Depressive symptoms having a cesarean section and high maternal education were correlated with dysfunctional problems in several subdomains. CONCLUSIONS: Findings indicated that women at risk of FSD differed significantly in aspects of partnership quality, breastfeeding, mode of delivery, maternal education, and depressive symptoms. Aspects of perinatal sexuality should be routinely implemented in the counseling of couples in prenatal classes.


Assuntos
Comportamento Sexual/psicologia , Disfunções Sexuais Psicogênicas/epidemiologia , Adulto , Aleitamento Materno/efeitos adversos , Cesárea/efeitos adversos , Depressão , Depressão Pós-Parto/complicações , Feminino , Humanos , Estudos Longitudinais , Período Pós-Parto , Gravidez , Terceiro Trimestre da Gravidez , Prevalência , Fatores de Risco , Disfunções Sexuais Psicogênicas/etiologia , Sexualidade/psicologia
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