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1.
Reprod Toxicol ; : 108588, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615785

RESUMO

The placental cholinergic system; known as an important factor in intracellular metabolic activities, regulation of placental vascular tone, placental development, and neurotransmission; can be affected by persistent organic pesticides, particularly organochlorine pesticides(OCPs), which can influence various epigenetic regulations and molecular pathways. Although OCPs are legally prohibited, trace amounts of the persistent dichlorodiphenyltrichloroethane(DDT) are still found in the environment, making prenatal exposure inevitable. In this study, the effects of 2,4'-DDT and 4,4'-DDT; and its breakdown product 4,4'-DDE in the environment on placental cholinergic system were evaluated with regards to cholinergic genes. 40 human placentas were screened, where 42,50% (17 samples) were found to be positive for the tested compounds. Average concentrations were 10.44µg/kg; 15.07µg/kg and 189,42µg/kg for 4,4'-DDE; 2,4'-DDT and 4,4'-DDT respectively. RNA-Seq results revealed 2396 differentially expressed genes in positive samples; while an increase in CHRM1,CHRNA1,CHRNG and CHRNA2 genes at 1.28, 1.49, 1.59 and 0.4 fold change were found(p<0,028). The increase for CHRM1 was also confirmed in tissue samples with immunohistochemistry. In vitro assays using HTR8/SVneo cells; revealed an increase in mRNA expression of CHRM1, CHRM3 and CHRN1 in DDT and DDE treated groups; which was also confirmed through western blot assays. An increase in the expression of CHRM1,CHRNA1, CHRNG(p<0,001) and CHRNA2(p<0,05) were found from the OCPs exposed and non exposed groups.The present study reveals that intrauterine exposure to DDT affects the placental cholinergic system mainly through increased expression of muscarinic receptors. This increase in receptor expression is expected to enhance the sensitivity of the placental cholinergic system to acetylcholine.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38286413

RESUMO

BACKGROUND: Several musculoskeletal changes occur in pregnancy, particularly in the abdominal region. The aim of this study was to search and compare the effects of long (LEP) and short exercise programs (SEP) in terms of the satisfaction of the needs of pregnant women. METHODS: This study consisted of 2 groups: LEP (n=16) and SEP (n=16). Muscle thickness measurements determined by ultrasound, the 6 minute walk test, Pregnancy Physical Activity Questionnaire, Visual Analogue Scale, Oswestry Disability Index, and Short Form-36 Quality of Life Questionnaire were the study variables. Evaluations were done at the 16th (baseline), 24th, and 32nd gestational weeks. The LEP consisted of 20 and the SEP consisted of 9 exercises, which were applied for 16 weeks until the 32nd gestational week. RESULTS: Emotional role limitation and pain scores of quality of life, 6 minute walk test, and occupational physical activity were found to be better in the LEP group at the 24th gestational week (p=0.043, p=0.049, p=0.049, p=0.026). At the 32nd gestational week, the 6 minute walk test and occupational physical activity were found to be higher in the LEP group (p=0.006, p=0.017). Additionally, rectus abdominis and bilateral diaphragm muscle thicknesses, "moderate intensity and sports physical activity" and "vitality and emotional well-being" were increased over time with the LEP (p+<+0.05 for all). On the other hand, unilateral diaphragm muscle thickness, sports physical activity level, and vitality were improved with the SEP (p+<+0.05 for all). CONCLUSIONS: The SEP and LEP both have beneficial effects in pregnant women. However, the LEP increases physical activity level, functional capacity, and quality of life more than the SEP during the later stages of pregnancy.

3.
Int J Environ Health Res ; : 1-10, 2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38007699

RESUMO

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT4) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (ß = 0.26; p = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health.

4.
Health Care Women Int ; : 1-18, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566684

RESUMO

This trial was carried out to investigate the effect of forced air warming in various body areas of women on hypothermia during cesarean delivery. The patients in the study groups (n = 76) were assigned to the full-body warming group, upper-extremity warming group, lower-extremity warming group, and control groups. The intervention groups received forced-air warming 30 min before the surgery and continued until 30 min after surgery. The incidence of hypothermia was significantly higher in the control group than in the other groups at the 60th minute of the operation (p < 0.01). The intervention and control groups showed significant differences in the frequency of shivering at the entrance to the PACU (p = 0.001). Thermal comfort scores have significant difference between the control group and all of the intervention groups (p<.001). It is said that the full-body forced-air warming technique prevents hypothermia, shivering, and thermal discomfort in women Cesarean Section (CS).

5.
J Obstet Gynaecol Res ; 49(6): 1525-1531, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37004995

RESUMO

AIM: To present the first-year experience of fetal cardiac interventions (FCIs) in a tertiary referral hospital and to evaluate the outcomes. METHODS: This retrospective study consisted of four pregnant women who underwent fetal pulmonary or aortic balloon valvuloplasty between November 2020 and June 2021. The procedures were performed with a percutaneous cardiac puncture under the ultrasonography guidance. Gestational age at intervention, procedural success, complications, and perinatal outcomes were evaluated. Procedural complications defined as fetal bradyarrhythmia requiring treatment, pericardial effusion requiring drainage, balloon rupture, and fetal death. The procedure was considered technically successful if the valve was dilated with a balloon catheter. Ultimately successful procedure was defined as the discharge of infants alive with biventricular circulation. RESULTS: A total of 5 FCIs attempted between 26 + 3 and 28 + 2 gestational weeks. While the procedure was technically successful in 2 cases with pulmonary stenosis, both attempts were unsuccessful in the fetus with pulmonary atresia. Although the procedure was technically successful in the patient with critical aortic stenosis, it ultimately failed. No fetal death occurred in our series and there were no procedure-related significant maternal complications. However, three interventions were complicated by fetal bradycardia and pericardial effusion necessitating treatment, and balloon rupture cropped up in one case. CONCLUSION: FCIs may lead to improving the likelihood of a biventricular outcome for selected fetuses. Careful selection of patients and centralization of experience are essential for obtaining favorable outcomes. Operators should be aware of procedural complications. Improved procedural techniques with a lower complication rate will be achieved through advanced medical technology and special balloon catheters.


Assuntos
Estenose da Valva Aórtica , Derrame Pericárdico , Lactente , Gravidez , Humanos , Feminino , Centros de Atenção Terciária , Estudos Retrospectivos , Turquia/epidemiologia , Coração Fetal/diagnóstico por imagem , Coração Fetal/cirurgia , Ultrassonografia Pré-Natal/métodos , Estenose da Valva Aórtica/cirurgia , Morte Fetal , Resultado do Tratamento
6.
Metabolomics ; 19(5): 45, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37084096

RESUMO

INTRODUCTION: Pregnancy complications, as preeclampsia (PE) and HELLP syndrome, occurring with similar pathophysiological mechanisms, have adverse effects on the health of both mother and fetus during pregnancy and thereafter, they are leading causes of maternal and fetal morbidity and mortality. The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information to be able to assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. OBJECTIVE: The aim of this study was to investigate the hair metabolome profile of pregnant women with PE, HELLP syndrome and healthy women. METHOD: Hair samples of new-borns' mothers (patients and controls) were investigated segmentally relevant to each trimester using a proper sample preparation and gas chromatography-mass spectrometry (GC-MS) to identify robust biomarkers that can be useful for screening, early detection, follow-up and treatment of PE and HELLP syndrome, the etiology of which are still unknown. RESULTS: The results showed a significant change in the metabolome profiles of the patient and control groups regarding the trimesters. A striking decrease was observed in all 100 metabolites investigated in the patient group (p < 0.000). The metabolic pathways associated with significant metabolites have also been investigated, and the most affected pathways were observed to be the urea cycle, glycine, serine, aspartate, methionine and purine metabolism, ammonia cycle, and phosphatidylethanolamine biosynthesis. CONCLUSION: The found metabolites provide us with extensive data on the ability to establish biomarkers for predicting, early detection and monitoring of PE.


Assuntos
Síndrome HELLP , Pré-Eclâmpsia , Complicações na Gravidez , Feminino , Gravidez , Humanos , Gestantes , Síndrome HELLP/diagnóstico , Metabolômica , Pré-Eclâmpsia/diagnóstico , Cabelo , Biomarcadores
7.
Artigo em Inglês | MEDLINE | ID: mdl-36746073

RESUMO

OBJECTIVES: The reproductive health of patients with Takayasu's arteritis (TA) is an important issue. Systemic inflammation and treatments used in TA may affect female reproductive organs, leading to infertility, maternal and fetal morbidity, and early menopause. This study aimed to evaluate fertility, early menopause and pregnancy outcomes of patients before and after TA diagnosis. In addition, pregnancy morbidities following TA diagnosis were analysed for each cluster. STUDY DESIGN: Two hundred and two patients with TA (184 females) who met the 1990 American College of Rheumatology criteria were registered in the prospective database of Hacettepe University Vasculitis Research Centre by the end of February 2020. Demographic and clinical features, comorbidities, distribution of vascular involvement, obstetric histories and outcomes were evaluated retrospectively. Patients with TA were classified according to novel proposed disease clusters. Early menopause was defined as menopause before 45 years of age. RESULTS: One hundred and twenty-one female patients with TA, for whom gynaecological records and marriage status could be obtained, were included in the study. Ninety-seven patients were married, of whom 12 (12.5 %) patients were infertile. In total, there were 238 pregnancies in 83 female patients with TA: 203 before TA diagnosis, 35 after TA diagnosis, and two patients were diagnosed during pregnancy. Compared with the pre-diagnosis group, maternal complications were significantly more common in the post-diagnosis group [23 (11.3 %) vs 9 (25.7 %); p = 0.048]. The most common maternal complication was gestational hypertension (12.1 %). Fetal complications were common in both groups (21.5 % pre-diagnosis vs 34.2 % post-diagnosis; p = 0.18), and included prematurity, intrauterine growth retardation and low birth weight. According to novel disease subsets, post-diagnosis patients were classified as C1 (n = 3, 15.7 %), C2 (n = 9, 47.3 %) or C3 (n = 6, 31.5 %). One patient could not be classified. There was no difference in obstetric outcomes between these subgroups. Early menopause was observed in 20 (16.5 %) of 121 patients, but some patients had not yet reached 45 years of age. CONCLUSION: Infertility was higher in patients with TA in comparison with the general population in Turkey (12.5% vs 8.6%), and the early menopause rate was lower in patients with TA (16.7% vs 36.1%). Pregnancies following a diagnosis of TA had more maternal complications than pre-diagnosis pregnancies. Fetal complications were more common both pre- and post-diagnosis. Chronic inflammation before TA diagnosis may lead to increased infertility and fetal complications.


Assuntos
Infertilidade , Arterite de Takayasu , Gravidez , Humanos , Feminino , Resultado da Gravidez , Arterite de Takayasu/complicações , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/diagnóstico , Estudos Retrospectivos , Fertilidade , Inflamação , Menopausa
8.
Eur J Med Genet ; 65(12): 104631, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36195292

RESUMO

Glycine encephalopathy with normal serum glycine (MIM #617301), also known as GLYT1 encephalopathy, is an extremely rare disorder caused by biallelic variants in SLC6A9 and characterised by facial dysmorphic features, skeletal findings including contractures, knee hyperextension, and joint dislocations and seizures. To date, only ten patients from five families have been reported and only two of them could survive until childhood. In this study, we report on a consanguineous Turkish couple with a history of six pregnancies with three habitual abortions and three postpartum exitus. While in three pregnancies the babies were born prematurely at 32nd gestational week by emergency ceserean section due to hydrops and fetal distress, the other pregnancy was medically terminated at 16th gestational week due to absent fetal heart activity. The product of all these three pregnancies exhibited similar phenotype including short neck, thoracic kyphosis, hypertrichosis, joint contractures and dislocations, hypertonia, knee hyperextension and facial dysmorphic features. Trio exome sequencing was performed prenatally during the last pregnancy and a novel VUS variant in SLC6A9 and a likely pathogenic variant in MTOR gene were detected. DNA isolation was performed from frozen muscle and adrenal tissue of previously autopsied fetuses with similar clinical features, and the same variants were confirmed in both of them. Our data suggest that SLC6A9 and MTOR variants may be responsible for this extremely lethal phenotype in this family.


Assuntos
Artrogripose , Encefalopatias , Contratura , Gravidez , Feminino , Humanos , Artrogripose/genética , Artrogripose/patologia , Sequenciamento do Exoma , Contratura/genética , Serina-Treonina Quinases TOR/genética
9.
Chemosphere ; 301: 134470, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35367487

RESUMO

Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals (EDCs). Their presence in the environment is particularly concerning in cases of fetal exposure, which is the most vulnerable period of life for both human and animals who share the same environment. Placenta, as a sample collected using noninvasive methods to screen EDCs, is a good indicator for potential fetal exposure. Although recent studies indicate that companion animal may correspond to human exposure, species-specific anatomo-morphological and metabolic differences are controversial. In this study, placenta samples of 60 women and 25 dogs living and giving birth within the same region were evaluated for the presence of PCB, OCP, PBDE, and PAH residues; where, socio-demographic factors were also assessed to identify the possible sources. Gas chromatography-mass spectrometry method was validated for the matrix, and among 45 screened and targeted pollutants, only 18 were found in human placentas. While the most frequently detected pollutants were DDTs, followed by PAHs and PCBs in decreasing order, the pollutants with the highest concentrations were PAHs, followed by PCBs and DDTs. Only five of the target contaminants were detected in the dog placentas. These results indicate that; as dogs have different bioaccumulation capacities and higher excretion rates than humans, the life-long effects of exposure to endocrine compound and possible consequences related to adverse health outcomes are expected to vary and concentrations cannot be directly correlated.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Hidrocarbonetos Policíclicos Aromáticos , Animais , Cães , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Feminino , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/toxicidade , Humanos , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Praguicidas/toxicidade , Placenta/metabolismo , Bifenilos Policlorados/análise , Bifenilos Policlorados/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Gravidez
10.
J Matern Fetal Neonatal Med ; 35(20): 3998-4003, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33231495

RESUMO

BACKGROUND: Amniotic fluid (AF) is a dynamic liquid whose contents vary according to the needs of the fetus. Levels of the amniotic components have been used in numerous studies as potential biomarkers to screen pregnancy-related abnormalities. As a reflection of Na+ and Cl- levels of fetal lung fluid, amniotic fluid's Na+ and Cl- levels can be used as an indicator of lung maturation in the newborn period. This study aimed to investigate whether Na+ and Cl- levels in the amniotic fluid would be a new marker to determine the severity of respiratory distress and pulmonary maturation in the newborn. METHODS: This prospective cohort study was conducted at Hacettepe University Neonatal Intensive Care Unit. One hundred twenty single infants who were delivered with the cesarean section between January 2015 and March 2016 were included. Na+ and Cl- levels were measured from AF. RESULTS: There were 46 of 120 infants (33.3%) in Group-1 and 74 infants (66.7%) in Group-2. Na + and Cl- levels of the AF of Group-1 were higher than Group 2 and this was statistically significant (p < .001/p: .01, respectively). Na+ and Cl- levels of the AF were significantly higher in infants who needed surfactant (p < .001/p: .001, respectively). CONCLUSION: Our results showed that Na+ and Cl- levels of the AF can be used as an indicator of infant lung maturation.


Assuntos
Líquido Amniótico , Síndrome do Desconforto Respiratório do Recém-Nascido , Biomarcadores , Cesárea , Cloretos , Cloro , Feminino , Humanos , Recém-Nascido , Pulmão , Gravidez , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Sódio
11.
Fetal Pediatr Pathol ; 41(5): 843-851, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34622726

RESUMO

Introduction: One-third of fetal soft tissue tumors are malignant and include congenital fibrosarcoma (CF). We report two fetal CFs arising in the posterior mediastinum. Case Presentation: In case 1, the CF resulted in a mediastinal shift, extensive infiltration of the tumor around adjacent structures, pulmonary hypoplasia, pleural effusion, and rapid growth. The pregnancy was terminated. Case 2 had multiple intrathoracic masses, thoracic hypoplasia, pleural effusion, and fetal death. Both were diagnosed as fibrosarcoma at fetopsy. Discussion: Although congenital CF tends to be locally aggressive with a low metastatic rate, it tends to grow rapidly and the tumor location can affect fetal survival. In Case 1, the tumor demonstrated locally aggressive behavior whereas multiple distant metastases such as lung, liver, adrenals, and left eye were detected in Case 2. The tumor was directly responsible for intrauterine fetal demise in the second case.


Assuntos
Fibrossarcoma , Derrame Pleural , Neoplasias de Tecidos Moles , Feminino , Feto/patologia , Fibrossarcoma/diagnóstico , Fibrossarcoma/patologia , Humanos , Mediastino/patologia , Gravidez , Neoplasias de Tecidos Moles/diagnóstico
12.
Congenit Anom (Kyoto) ; 61(6): 208-211, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34273127

RESUMO

Congenital esophageal web is a very rare type of esophageal atresia (EA) and is considered as Type IV atresia in Kluth's classification. Type IV EA is further classified into subgroups according to the location of web and the presence of tracheoesophageal fistula (TEF). Herein, we present a newborn having Type IV1a EA who was initially suspected as isolated EA and has co-existing malrotation together with the review of the literature. A newborn having congenital esophageal web was admitted with antenatal ultrasonography revealing polyhydramnios, dilated stomach, and duodenum. Abdominal X-ray revealed a gasless abdomen suggesting isolated EA. The upper gastrointestinal series confirmed complete obstruction at the lower esophagus. Bronchoscopy performed excluding TEF. Laparotomy revealed intestinal malrotation and the absence of another GI webs. Gastrotomy was performed and mucosal web at GEJ was seen by pushing nasogastric catheter. Web excision and Ladd procedure were performed. Congenital esophageal web is an extremely rare type of esophageal anomaly that can be only classified in Kluth classification. A high index of suspicion is required for diagnosis especially in newborns with the gasless abdomen and esophageal obstruction at the level of GEJ. Preoperative bronchoscopy is mandatory to exclude an associating TEF. Surgical exploration via laparotomy is beneficial for exploring additional GIS anomalies.


Assuntos
Anormalidades do Sistema Digestório , Atresia Esofágica , Fístula Traqueoesofágica , Atresia Esofágica/diagnóstico por imagem , Atresia Esofágica/cirurgia , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Fístula Traqueoesofágica/diagnóstico por imagem , Fístula Traqueoesofágica/cirurgia , Ultrassonografia Pré-Natal
13.
Arch Gynecol Obstet ; 304(1): 125-130, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33433702

RESUMO

PURPOSE: In December 2019, the emerging of a novel coronavirus (COVID-19) has influenced the whole world. The current pandemic also triggers several psychological changes. Uncertainties and changes in health practices may cause anxiety, depression, and concerns on vulnerable populations such as pregnant. This study aims to survey the pregnant women to capture the psychological impact and perceptions during the pandemic. METHODS: A total of 297 pregnant women aged ≥ 18 years were enrolled in May 2020. We evaluated the hard-copy survey included questions about demographic and clinical information of patients, 95% confidence intervals of a COVID-19-related questionnaire in a Likert scale and 14-item Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 297 pregnant women were included in this study with a mean age of 27.64. Most patients (82.5%) had concerns about infecting their babies during delivery. The fear of infection of the fetus during delivery revealed elderly age and having anxiety as the unique significant risk factors. Mean HADS-A and HADS-D scores were 7.94 (± 4.03) and 7.23 (± 3.84), respectively. Multivariate analysis showed having anxiety was associated with a high HADS-D score and concern about the inability to reach obstetrician, and being in advanced age, having a high HADS-A score, and concern about the inability to reach obstetrician demonstrated significant effects on HADS-D score. CONCLUSION: We conclude that in future pandemics, communications and reassurance of the patients should be prioritized upon their routine ante-natal care to avoid increased levels of anxiety and even depression.


Assuntos
Ansiedade/epidemiologia , COVID-19/psicologia , Depressão/epidemiologia , Medo/psicologia , Pandemias , Gestantes/psicologia , Adulto , Idoso , Ansiedade/psicologia , Transtornos de Ansiedade , COVID-19/epidemiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , SARS-CoV-2 , Estresse Psicológico , Inquéritos e Questionários
14.
Fetal Pediatr Pathol ; 40(3): 189-197, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31696754

RESUMO

OBJECTIVE: We evaluated the association of nuchal translucency (NT) values above 99th percentile with perinatal outcomes. Materials and methods: Singleton pregnancies with NT values above 99th percentile were investigated. Pregnancies were divided into 3 groups: group 1, NT = 2.6-<3.5 mm; group 2, NT = 3.5-4.5 mm; and group 3, NT > 4.5 mm. Demographic features, clinical characteristics, structural/chromosomal anomaly rates and perinatal outcomes were compared. Results: Normal ultrasonographic anatomy was found in 47.5%, 7.7%, and 14.3% of groups 1, 2, and 3, respectively (p = 0.006). Group 3 had the lowest normal karyotype rate (44.6%) (p = 0.005). Higher frequencies for both miscarriage and pregnancy termination were observed in group 3 compared to group 1 (8.9% vs. 4.9% and 66.1% vs. 32.7%, respectively) (p = 0.02). The lowest rate of normal postnatal anatomic findings was found in group 3 (10.7%) (p = 0.01). Conclusion: NT values above 99th percentile for gestational age seem to be associated with increased rates of chromosomal/structural abnormalities and adverse perinatal outcomes.


Assuntos
Medição da Translucência Nucal , Resultado da Gravidez , Aberrações Cromossômicas , Feminino , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez
15.
Neuropeptides ; 80: 102029, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32127176

RESUMO

Differentiation, self-renewal and quiescence of Hematopoietic stem cells (HSCs) is tightly regulated in order to protect the HSCs from the strain of constant cell division and depletion of the stem cell pool. The neurotransmitter Neuropeptide Y (NPY) is released from sympathetic nerves in the bone marrow and has been shown to indirectly affect HSC function through effects on bone marrow (BM) multipotent Mesenchymal Stromal Cells (MSCs), osteoblasts (OBs) and macrophages. Although the absence of NPY has been shown to be accompanied by severe BM impairment and delayed engraftment of HSCs, the direct effects of NPY on HSCs have never been assessed. Here, we aimed to explore the effect of NPY on the regulation of HSCs. All NPY receptors Y1, Y2, Y4 and Y5 were found to be highly expressed on most HSCs and mature hematopoietic cell subsets. In culture, in particularly expression of the Y1 receptor was shown to decrease in time. Doses of 300 nM NPY suppressed HSC proliferation in cell cultures, as confirmed by an increase of HSCs in G0 phase and an increase in the gene expression levels of FOXO3, DICER1, SMARCA2 and PDK1, which all have been shown to play an important role in the regulation of cell quiescence. These data support the idea that NPY may have a direct effect on the regulation of HSC fate by modulating cell quiescence.


Assuntos
Proliferação de Células/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Neuropeptídeo Y/farmacologia , Receptores de Neuropeptídeo Y/metabolismo , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Neuropeptídeo Y/metabolismo , Receptores de Neuropeptídeo Y/efeitos dos fármacos
16.
Biol Blood Marrow Transplant ; 26(4): 634-642, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31917271

RESUMO

The newly developed 6-hydroxychromanol derivate SUL-109 was shown to provide protection during hypothermic storage of several cell lines, but has not been evaluated in hematopoietic stem cells (HSCs). Hypothermic preservation of HSCs would be preferred over short-term cryopreservation to prevent cell loss during freezing/thawing and would be particularly useful for short-term storage, such as during conditioning of patients or transport of HSC transplants. Here we cultured human CD34+ umbilical cord blood (UCB) cells and lineage-depleted (Lin-) Balb/c bone marrow (BM) cells for up to 7 days in serum-free HSC expansion medium with hematopoietic growth factors. SUL-109-containing cultures were stored at 4°C for 3 to 14 days. The UCB cells were tested for viability, cell cycle, and reactive oxygen species (ROS). DMSO-cryopreserved Lin- BM cells or Lin- BM cells maintained for 14 days at 4°C were transplanted into RAG2-/- Balb/c mice and engraftment was followed for 6 months. The addition of SUL-109 during the hypothermic storage of expanded CD34+ UCB cells provided a significant improvement in cell survival of the immature CD34+/CD38- fraction after 7 days of hypothermic storage through scavenging of hypothermia-induced ROS and was able to preserve the multilineage capacity of human CD34+ UCB cells for up to 14 days of cold storage. In addition, SUL-109 protected murine BM Lin- cells from 14 days of hypothermic preservation and maintained their engraftment potential after transplantation in immune-deficient RAG2-/- mice. Our data indicate that SUL-109 is a promising novel chemical for use as a protective agent during cold storage of human and murine HSCs to prevent hypothermia-induced apoptosis and promote cell viability.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hipotermia , Animais , Antígenos CD34 , Apoptose , Cromanos , Sangue Fetal , Células-Tronco Hematopoéticas , Humanos , Camundongos
17.
J Turk Ger Gynecol Assoc ; 21(3): 180-186, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564083

RESUMO

Objective: To evaluate perinatal outcomes in human immunodeficiency virus (HIV) infected pregnant women in Turkey. Material and Methods: Maternal characteristics, pregnancy complications, laboratory findings including HIV load, CD4 cell count, CD4/CD8 ratio, neonatal features and final HIV status of the baby were retrospectively analyzed. Results: The sample included 26 singleton pregnancies, from 25 HIV-infected women. The ethnicities were Turkish (n=18), East European (n=4), Asian (n=2) and African (n=2). The majority (76.9%) was aware of their HIV status before becoming pregnant. Four cases (15.3%) were diagnosed during pregnancy and two (7.8%) at the onset of labor. The results for median HIV viral load, CD4 count, and CD4/CD8 ratio at birth were 20 copies/mL (0-34 587), 577/mm3 (115-977), and 0.7 (0.1-1.9), respectively. The HIV viral load rate was 5.5% in eighteen women taking anti-retroviral treatment. The rates of gestational diabetes mellitus, gestational hypertension, intrauterine growth restriction, and preterm delivery were 3.8%, 3.8%, 7.6%, and 8% (numbers are 1;1;2;2), respectively. The mean gestational week at birth was 38 weeks and mean birthweight is 2972±329 g. Two babies were congenitally infected with HIV (infection rate of 8.3%). There was one needle-related accident during surgery. Conclusion: Timely diagnosis of HIV infection during pregnancy is important for preventing mother to child transmission. HIV infected women may give birth to HIV negative babies with the help of a multidisciplinary team, composed of perinatology, infectious diseases, and pediatrics specialists.

18.
J Matern Fetal Neonatal Med ; 33(3): 368-372, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29914284

RESUMO

Objective: We aimed to evaluate congenital heart disease (CHD) cases according to EUROCAT subgroup classification that were diagnosed during the prenatal period in our center.Methods: CHDs that were prenatally diagnosed using ultrasonography and confirmed by fetal echocardiography were reviewed over a 10-year period. Subgroup classification was finalized at the post-partum period in terms of the EUROCAT guide 1.3. Congenital heart defect subtypes and obstetric outcomes (gestational week at delivery, birth weight, gender, extracardiac structural abnormalities, karyotype results if performed) were analyzed.Results: The data of 180 cases with CHD were examined. Left ventricular outflow tract obstruction (LVOT) was the most common CHD subtype (57/180; 31.6%), which included 48, five, and four cases of hypoplastic left heart syndrome (HLHS), coarctation of the aorta, and aortic valve atresia/stenosis, respectively. Eighteen pregnancies were terminated; the most common CHD subtype among patients of terminated pregnancies was hypoplastic left heart syndrome (HLHS) (n = 7, 38.8%). The most common extracardiac malformations were a single umbilical artery, esophageal atresia, and situs inversus in our study group. Eighteen of the 96 (18.75%) neonates with CHD died during the neonatal period. The most common CHD subtype was HLHS (7/18; 38%) among the newborns who died after birth.Conclusion: Prenatal diagnosis of a CHD and subgroup classification is very important for clinical decision making, including prenatal management, recommendations for termination of the pregnancy, postnatal management of the patient, and for early referral to pediatric cardiology and cardiovascular surgery centers.


Assuntos
Cardiopatias Congênitas/epidemiologia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Gravidez , Estudos Retrospectivos , Turquia/epidemiologia , Ultrassonografia Pré-Natal
19.
Reprod Toxicol ; 87: 146-155, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31170452

RESUMO

Bisphenol A (BPA) and phthalates can adversely affect the fetal development. However, observational studies on the effects of these chemicals on fetal male reproductive system are still limited. A hundred of umbilical cord blood samples were analyzed for the levels of BPA, di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and sex hormones. After birth, male newborns underwent physical examination that included measurements of anogenital distance, stretched penile length (SPL), and penile width. BPA, DEHP and MEHP levels were detectable in ≈99% of cord blood samples. In covariate-adjusted models, cord blood BPA levels were inversely associated with SPL of newborns and positively associated with cord blood estradiol levels. In addition, there was a significant inverse relationship between cord blood DEHP levels and anogenital distance index of newborn males. Our results suggest that in utero BPA and DEHP exposure exerted adverse effects on fetal male reproductive development and cord blood estradiol levels.


Assuntos
Compostos Benzidrílicos/análise , Dietilexilftalato/análogos & derivados , Dietilexilftalato/análise , Disruptores Endócrinos/análise , Poluentes Ambientais/análise , Sangue Fetal/química , Genitália Masculina/crescimento & desenvolvimento , Fenóis/análise , Adulto , Monitoramento Biológico , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Masculino , Exposição Materna , Troca Materno-Fetal , Gravidez , Fatores de Risco , Hormônios Tireóideos/sangue , Adulto Jovem
20.
Fetal Pediatr Pathol ; 38(4): 282-289, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30892123

RESUMO

Objective: To evaluate and compare the outcomes of pregnancies with prenatally detected gastroschisis and omphalocele. Materials and Methods: We retrospectively evaluated prenatally detected gastroschisis and omphalocele cases. Cases were compared in terms of maternal demographic and clinical characteristics as well as pregnancy and neonatal outcomes. Results: This study consisted of 17 gastroschisis and 30 omphalocele cases. Only one case with gastroschisis was terminated due to additional severe limb deformities. Seventeen out of 30 cases of omphalocele were terminated for various reasons (56.7%). All patients with gastroschisis had surgical repair, while 8 out of 13 omphalocele cases had surgery. One patient with an omphalocele died after surgery due to sepsis. Six cases of gastroschisis also died in the neonatal period due to various reasons (6/16, 37.5%). Conclusion: Additional genetic disorders are more frequent in those with omphalocele cases, and they are more frequently terminated during gestation that the gastroschisis fetuses.


Assuntos
Gastrosquise/diagnóstico por imagem , Gastrosquise/embriologia , Hérnia Umbilical/diagnóstico por imagem , Hérnia Umbilical/embriologia , Diagnóstico Pré-Natal , Adolescente , Adulto , Anormalidades Congênitas/diagnóstico por imagem , Anormalidades Congênitas/genética , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Cariotipagem , Idade Materna , Mães , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Adulto Jovem
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