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1.
Artigo em Inglês | MEDLINE | ID: mdl-36239587

RESUMO

OBJECTIVE: To determine the effect of preeclampsia on the development of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Retrospective cohort study of infants' ≤32 weeks' gestation admitted to a level-IV single center neonatal intensive care unit from 2014 to 2016. Infants with major congenital anomalies, death or transfer before 28 days were excluded. Infants were stratified by maternal preeclampsia status. Demographic, clinical, and laboratory data were reviewed. Logistic regression was used to examine predictors for BPD. MAIN OUTCOME MEASURE: The primary outcome was BPD incidence. RESULTS: 432 infants met inclusion criteria; 22% developed BPD, of which, 16% had severe BPD. Thirty-eight percent of infants were born to preeclamptic mothers, with 23% of those infants developing BPD. Infants born to preeclamptic mothers were delivered by cesarean section (88% vs. 60%; p<0.0001) more often and had lower birthweight (Median=1265g, IQR 910-1555 vs. Median=1388g, IQR 959-1752; p=0.008) compared to infants born to non-preeclamptic mothers. Higher incidence of intrauterine growth restriction was noted in pre-eclampsia group,24% vs 8%, p=0.0001). Gestational age, length of stay and days on ventilator were all associated with the development of BPD. In multivariable logistic regression, preeclampsia was not a risk factor for development of BPD (OR 1.12 [0.68, 1.83]). CONCLUSIONS: Preeclampsia was not a significant risk factor for development of BPD nor the severity of BPD in infants' ≤32 weeks' gestation. IUGR infants with or without preeclampsia mothers were at higher risk for BPD.

2.
Obstet Gynecol Surv ; 74(2): 111-125, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30756125

RESUMO

IMPORTANCE: Pregnancy is getting more and more complex due to increasing number of complications that may affect fetal outcomes. The introduction of newer "proteomics and metabolomics" technologies in the field of obstetrics and gynecology may allow physicians to identify possible associated etiologies that affect the mother during pregnancy and lead to associated complications affecting the offspring. OBJECTIVE: The principal objective of this review article is to provide a comprehensive evaluation of the use of proteomics and metabolomics in complicated pregnancies. Future studies that incorporate data from multiple technologies may allow the development of an integrated biological system approach to maternal genomes, proteomes, and metabolomes in pregnancy. EVIDENCE ACQUISITION AND RESULTS: We conducted a substantial MEDLINE, EBSCOhost, and Cochrane database search for all the relevant articles containing use of "omics" technologies in pregnancy. We identified 197 relevant articles, following standardized systematic review process along with grading systems; 69 eligible articles were identified. CONCLUSION/RELEVANCE: We sought to provide a comprehensive review in this emerging field of "omics" in pregnancy and associated complications. This article focuses mainly on use of proteomics and metabolomics identification techniques and possible interventions for early pregnancy complications to improve neonatal outcomes.


Assuntos
Metabolômica/métodos , Complicações na Gravidez/metabolismo , Proteômica/métodos , Feminino , Humanos , Gravidez
3.
Sci Rep ; 9(1): 133, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644421

RESUMO

Hydrogen peroxide (H2O2) plays an important role physiologically as the second messenger and pathologically as an inducer of oxidative stress in injury, ischemia and other conditions. However, it is unclear how H2O2 influences various cellular functions in health and disease differentially, particularly in the blood-brain barrier (BBB). We hypothesized that the change in cellular concentrations of H2O2 is a major contributor in regulation of angiogenesis, barrier integrity/permeability and cell death/apoptosis in BBB endothelial cells. Rat brain microvascular endothelial cells were exposed to various concentrations of H2O2 (1 nM to 25 mM). BBB tight junction protein (zonula ocludens-1; ZO-1) localization and expression, cytoskeletal organization, monolayer permeability, angiogenesis, cell viability and apoptosis were evaluated. H2O2 at low concentrations (0.001 µM to 1 µM) increased endothelial cell tube formation indicating enhanced angiogenesis. H2O2 at 100 µM and above induced monolayer hyperpermeability significantly (p < 0.05). H2O2 at 10 mM and above decreased cell viability and induced apoptosis (p < 0.05). There was a decrease of ZO-1 tight junction localization with 100 µm H2O2, but had no effect on protein expression. Cytoskeletal disorganizations were observed starting at 1 µm. In conclusion H2O2 influences angiogenesis, permeability, and cell death/apoptosis in a tri-phasic and concentration-dependent manner in microvascular endothelial cells of the blood-brain barrier.


Assuntos
Barreira Hematoencefálica/patologia , Células Endoteliais/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/patologia , Neovascularização Patológica/induzido quimicamente , Permeabilidade/efeitos dos fármacos , Ratos , Junções Íntimas/efeitos dos fármacos
4.
J Investig Med ; 66(4): 728-732, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29170244

RESUMO

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan's post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.


Assuntos
Diabetes Gestacional/patologia , Pré-Eclâmpsia/patologia , Adulto , Peso ao Nascer , Estudos Transversais , Diabetes Gestacional/fisiopatologia , Diástole , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/fisiopatologia , Gravidez , Estudos Retrospectivos , Sístole
5.
Proc (Bayl Univ Med Cent) ; 30(4): 459-460, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28966466

RESUMO

Congenital midline nasal anomalies are rare, with a prevalence of 1 in 20,000 to 40,000 births and with 5% to 7% of them being nasal glioma. Differential diagnoses of nasal anomalies include nasal dermoid cysts, gliomas, encephaloceles, nasal polyps, and some other rare anomalies. Due to current medical technological advancements, most of these anomalies are easily correctable, though delaying management may lead to fatal effects. This report describes two cases-one of nasal glioma and one of nevus lipomatosus cutaneous superficialis-that presented as respiratory distress in a newborn. Approximately 10 to 20 cases of these two conditions have been described; notably, this is the second documented case of nevus lipomatosus cutaneous superficialis with nasal presentation.

6.
BMC Res Notes ; 10(1): 42, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-28086969

RESUMO

BACKGROUND: In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. METHODS: We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. RESULTS: A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. CONCLUSIONS: Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Humanos , Recém-Nascido
7.
J Biol Chem ; 291(53): 26958-26969, 2016 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-27875293

RESUMO

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema are hallmark features of several brain pathologies, including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1ß (IL-1ß) that is up-regulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability, but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain. In these studies, rat brain microvascular endothelial cell monolayers exposed to calpain inhibitors (calpain inhibitor III and calpastatin) or transfected with calpain-1 siRNA demonstrated attenuation of IL-1ß-induced monolayer hyperpermeability. Calpain inhibition led to protection against IL-1ß-induced loss of zonula occludens-1 (ZO-1) at the tight junctions and alterations in F-actin cytoskeletal assembly. IL-1ß treatment had no effect on ZO-1 gene (tjp1) or protein expression. Calpain inhibition via calpain inhibitor III and calpastatin decreased IL-1ß-induced calpain activity significantly (p < 0.05). IL-1ß had no detectable effect on intracellular calcium mobilization or endothelial cell viability. Furthermore, calpain inhibition preserved BBB integrity/permeability in a mouse controlled cortical impact model of TBI when studied using Evans blue assay and intravital microscopy. These studies demonstrate that calpain-1 acts as a mediator of IL-1ß-induced loss of BBB integrity and permeability by altering tight junction integrity, promoting the displacement of ZO-1, and disorganization of cytoskeletal assembly. IL-1ß-mediated alterations in permeability are neither due to the changes in ZO-1 expression nor cell viability. Calpain inhibition has beneficial effects against TBI-induced BBB hyperpermeability.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Calpaína/antagonistas & inibidores , Permeabilidade da Membrana Celular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Glicoproteínas/farmacologia , Animais , Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/metabolismo , Calpaína/genética , Calpaína/metabolismo , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Interleucina-1beta/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Ratos
8.
Proc (Bayl Univ Med Cent) ; 29(4): 387-388, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27695169

RESUMO

Bilateral congenital pseudoarthrosis of the clavicles is extremely rare. We report a case of this entity presenting in the neonatal period. We highlight the importance of the differential diagnosis when clavicular fracture shows no evidence of healing or occurs bilaterally.

9.
BBA Clin ; 6: 25-30, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27335802

RESUMO

OBJECTIVE: Preeclampsia (preE) has a significant link to alterations of placental function leading to stress and apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring. We assessed apoptotic signaling in placentas and umbilical cords from patients with and without preE. METHODS: We collected placental and cord tissues from 27 normal pregnant (NP) women and 20 preE consenting patients after delivery in an IRB approved prospective study. p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-apoptotic Bcl-2-associated X (Bax), anti-apoptotic Bcl-2, caspase-9, and pro-inflammatory cyclooxygenase-2 (Cox-2) were evaluated by western blot and immunohistochemistry. Comparisons were performed using Student's t-test. RESULTS: p38 phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold), ratio of Bax/Bcl-2 (Placenta: 1.7 fold, Cord: 2.2 fold), caspase-9 (Placenta: 1.5 fold, Cord: 1.8 fold) and Cox-2 (Placenta: 2.5 fold, Cord: 2.3 fold) were up-regulated (p < 0.05) in preE compared to NP patients. Average hospital stays for preE babies were longer than NP babies. No complications were reported for NP babies; however, all of preE babies had multiple complications. CONCLUSIONS: Apoptotic and stress signaling are augmented in preE placenta and cord tissue that alter the intrauterine environment and activates the detrimental signaling that is transported to fetus.

10.
PLoS One ; 11(5): e0154427, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27152411

RESUMO

Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1ß (IL-1ß) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1ß (10 ng/mL; 2 hours)-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 µg/mL; 1 hour), GM6001 (broad spectrum MMP inhibitor; 10 µM; 1 hour), MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour) or MMP-9 siRNA transfection (48 hours) in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1ß-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1ß treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB hyperpermeability in a mouse model of TBI indicating its potential as a therapeutic agent for brain edema when established in humans.


Assuntos
Barreira Hematoencefálica , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Melatonina/fisiologia , Inibidores de Proteases/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/uso terapêutico , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Ratos
11.
Am J Perinatol ; 33(14): 1337-1356, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27159203

RESUMO

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.


Assuntos
Quimiocinas/metabolismo , Hormônios/metabolismo , Inflamação/fisiopatologia , Complicações na Gravidez/imunologia , Receptores Toll-Like/metabolismo , Diabetes Gestacional/imunologia , Feminino , Retardo do Crescimento Fetal/imunologia , Humanos , Imunidade Celular , Imunidade Inata , Recém-Nascido , Obesidade/imunologia , Pré-Eclâmpsia/imunologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/imunologia
12.
Proc (Bayl Univ Med Cent) ; 29(2): 128-30, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27034542

RESUMO

This double-blinded, randomized, crossover study evaluated the safety and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC) transfusions versus 15 mL/kg aliquot transfusions in very low birth weight (VLBW) infants with anemia. The study enrolled 22 hemodynamically stable VLBW infants requiring PRBC transfusions, with a mean gestational age of 25.7 ± 2.2 weeks and birth weight of 804 ± 261 g. Each infant was randomized to receive one of two treatment sequences: 15 mL/kg followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants were monitored during and after transfusions, and the efficacy and safety of the treatments were evaluated. Infants had higher posttransfusion hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels (38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions when compared to 15 mL/kg transfusions. There were no differences in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign instability between groups. In conclusion, high-volume PRBC transfusions (20 mL/kg) were associated with higher posttransfusion hemoglobin and hematocrit levels but no adverse effects. Higher-volume transfusions may reduce the need for multiple transfusions and therefore the number of donors the infant is exposed to.

13.
AJP Rep ; 6(1): e42-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26929869

RESUMO

Introduction Preeclampsia (preE) is pregnancy-induced hypertension affecting a significant proportion of pregnant women worldwide and can cause detrimental effects in the mother and newborn. Some of the effects in the newborn include neonatal thrombocytopenia. Pertaining specifically to neonatal thrombocytopenia, several questions remain unanswered. Discussion According to the current literature, neonatal thrombocytopenia due to maternal preE is highly prevalent in the general population and the incidence is reported to be around 30% worldwide. This review gives an insight into the syndrome and summarizes the possible pathological mechanisms, the diagnostic approach, complications, and therapeutic interventions of neonatal thrombocytopenia. It also identifies the involvement of other cell lines, apart from platelets in the newborns. Furthermore, we suggest a future prospective study to investigate the pathogenesis of preE and plan a study involving animal models to come up with a possible therapeutic intervention to prevent preE and its various consequences in neonates.

14.
Mol Cell Biochem ; 405(1-2): 81-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25863494

RESUMO

Diabetes in pregnancy is associated with microvascular complications and a higher incidence of preeclampsia. The regulatory signaling pathways involving nitric oxide, cGMP, and cGMP-dependent protein kinase (PKG) have been shown to be down-regulated under diabetic conditions and contribute to the pathogenesis of vascular complications in diabetes. The present study was undertaken to investigate how high glucose concentrations regulate PKG expression in cytotrophoblast cells (CTBs). Human CTBs (Sw. 71) were treated with 45, 135, 225, 495, or 945 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (10 µM SB203580) or 10 µM rosiglitazone. After treatment, the cell lysates were subjected to measure the expression of protein kinase G1α (PKG1α), protein kinase G1ß (PKG1ß), soluble guanylate cyclase 1α (sGC1α), and soluble guanylate cyclase 1 ß (sGC1ß) by Western blot. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test. The expressions of PKG1α, PKG1ß, sGC1α, and sGC1ß were significantly down-regulated (p < 0.05) in CTBs treated with >135 mg/dL glucose compared to basal (45 mg/dL). The hyperglycemia-induced down-regulation of cGMP and cGMP-dependent PKG were attenuated by the SB203580 or rosiglitazone pretreatment. Exposure of CTBs to excess glucose down-regulates cGMP and cGMP-dependent PKG, contributing to the development of vascular complications in diabetic mothers during pregnancy. The attenuation of hyperglycemia-induced down-regulation of PKG proteins by SB203580 or rosiglitazone pretreatment further suggests the involvement of stress signaling mechanisms in this process.


Assuntos
Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , GMP Cíclico/metabolismo , Regulação para Baixo/fisiologia , Hiperglicemia/metabolismo , Primeiro Trimestre da Gravidez/metabolismo , Trofoblastos/metabolismo , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Feminino , Glucose/metabolismo , Guanilato Ciclase/metabolismo , Humanos , Imidazóis/farmacologia , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Piridinas/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Rosiglitazona , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Guanilil Ciclase Solúvel , Tiazolidinedionas/farmacologia , Trofoblastos/efeitos dos fármacos
15.
Am J Hypertens ; 28(10): 1277-84, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25767135

RESUMO

OBJECTIVE: Preeclampsia (preE), a syndrome of hypertension, proteinuria, and edema, has many elusive triggers. The renin-angiotensin system has been implicated in preE pathogenesis. In this study, we test the hypothesis that (pro)renin levels are increased in preE patients and that levels of (pro)renin and (pro)renin receptor ((P)RR) are elevated in a rat model of preE. METHODS: We recruited 30 preE and 43 normal pregnant consenting patients. We used normally pregnant rats (NP, n = 10) and pregnant rats receiving weekly injections of desoxycorticosterone acetate and whose drinking water was replaced with 0.9% saline (preE, n = 10). Plasma and placental levels of (pro)renin were assayed by ELISA. Placental and kidney (P)RR was measured both by immunoblotting and immunohistochemistry. RESULTS: The mean plasma (pro)renin of 27.1±5.2 in preE patients differs from that in patients without preE: 14.8±5.2 ng Ang I/ml/hour (P < 0.0001). In rats, both plasma (NP: 22.7±4.3 and preE: 49.2±10.0 ng Ang I/ml/hour) and placental (NP: 152±24 and preE: 302±39 ng/g tissue) levels of (pro)renin were higher (P < 0.001) in preE compared to NP rats. (P)RR expression was greater (P < 0.05) in placental tissue of preE rats, while kidney (P)RR expression was similar. CONCLUSION: Elevated levels of circulating (pro)renin have been observed in preE patients and in a rat model of preE. We also found the increased expression of placental (P)RR in preE rats.


Assuntos
Pré-Eclâmpsia/sangue , Receptores de Superfície Celular/sangue , Renina/sangue , Adolescente , Adulto , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Rim/metabolismo , Placenta/metabolismo , Gravidez , Ratos , Regulação para Cima , Adulto Jovem , Receptor de Pró-Renina
16.
Transl Res ; 165(4): 449-63, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25468481

RESUMO

Pre-eclampsia (preE) is a multifaceted complication found uniquely in the pregnant patient and one that has puzzled scientists for years. PreE is not a single disorder, but a complex syndrome that is produced by various pathophysiological triggers and mechanisms affecting about 5% of obstetrical patients. PreE is a major cause of premature delivery and maternal and fetal morbidity and mortality. PreE is characterized by de novo development of hypertension and proteinuria after 20 weeks of gestation and affects nearly every organ system, with the most severe consequences being eclampsia, pulmonary edema, intrauterine growth restriction, and thrombocytopenia. PreE alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. The fetus has to adapt to this intrauterine environment with detrimental signals. The adaptive changes increase the risk of disease later in life. This review defines the predisposition and causes of preE and the cellular signaling detrimental to maternal health during preE. Moreover, the risk factors for diseases that are transmitted to the offspring have been addressed in this review. The detrimental signaling molecules that have been overexpressed in preE patients raises the possibility that those signals could be therapeutically blocked one day.


Assuntos
Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Feminino , Humanos , Pré-Eclâmpsia/etiologia , Gravidez , Fatores de Risco , Transdução de Sinais
17.
J Matern Fetal Neonatal Med ; 28(11): 1296-1301, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25164552

RESUMO

OBJECTIVE: Preeclampsia (preE) is a hypertensive disorder seen in 3-10% of human pregnancies and is diagnosed by de novo onset of hypertension and proteinuria. Several research groups provided evidence for reduced aldosterone (Aldo) and progesterone (Prog) availability in preE. The aim of this study was to determine the levels of Aldo and Prog in preE. METHODS: Normal pregnant (NP; n = 39) and preE (n = 30) patients were recruited to have their blood drawn between 21 and 40 weeks of pregnancy. Two groups of rats were used in this study: NP rats (n = 10) and preE rats (n = 10), which were given weekly injections of desoxycorticosterone acetate and 0.9% saline to drink. Aldo and Prog levels were assayed in plasma and urine samples by ELISA kits. RESULTS: In preE patients, the mean Aldo and Prog levels were suppressed (p < 0.05) compared to NP patients. NP patients exhibited a trend of increased levels of Aldo with an increase in gestational age; however, preE patients had the opposite trend. Both normal and preE patients exhibited a trend of increased levels of Prog with an increase in gestational age. The plasma and urinary Aldo and Prog levels were lower (p < 0.05) in preE rats compared to NP rats. CONCLUSIONS: We have demonstrated using a rat model and patients that both Aldo and Prog are suppressed in preE and thus may be used as biomarkers for preE.

18.
Int J Environ Res Public Health ; 11(7): 7456-69, 2014 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-25050653

RESUMO

A synthetic tripodal-based thiourea receptor (PNTTU) was used to explore the receptor/ligand binding affinity using CTB cells. The human extravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. The cell proliferation, migration and angiogenic factors were evaluated in PNTTU-treated CTB cells. The PNTTU inhibited the CTBs proliferation and migration. The soluble fms-like tyrosine kinase-1 (sFlt-1) secretion was increased while vascular endothelial growth factor (VEGF) was decreased in the culture media of CTB cells treated with ≥1 nM PNTTU. The angiotensin II receptor type 2 (AT2) expression was significantly upregulated in ≥1 nM PNTTU-treated CTB cells in compared to basal; however, the angiotensin II receptor, type 1 (AT1) and vascular endothelial growth factor receptor 1 (VEGFR-1) expression was downregulated. The anti-proliferative and anti-angiogenic effect of this compound on CTB cells are similar to the effect of CTSs. The receptor/ligand affinity of PNTTU on CTBs provides us the clue to design a potent inhibitor to prevent the CTS-induced impairment of CTB cells.


Assuntos
Receptores Artificiais/metabolismo , Tioureia/análogos & derivados , Tioureia/metabolismo , Trofoblastos/metabolismo , Linhagem Celular , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
19.
Microcirculation ; 21(2): 187-95, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24372803

RESUMO

OBJECTIVE: Microvascular hyperpermeability that occurs due to breakdown of the BBB is a major contributor of brain vasogenic edema, following IR injury. In microvascular endothelial cells, increased ROS formation leads to caspase-3 activation following IR injury. The specific mechanisms, by which ROS mediates microvascular hyperpermeability following IR, are not clearly known. We utilized an OGD-R in vitro model of IR injury to study this. METHODS: RBMEC were subjected to OGD-R in presence of a caspase-3 inhibitor Z-DEVD, caspase-3 siRNA or an ROS inhibitor L-AA. Cytochrome c levels were measured by ELISA and caspase-3 activity was measured fluorometrically. TJ integrity and cytoskeletal assembly were studied using ZO-1 immunofluorescence and rhodamine phalloidin staining for f-actin, respectively. RESULTS: OGD-R significantly increased monolayer permeability, ROS formation, cytochrome c levels, and caspase-3 activity (p < 0.05) and induced TJ disruption and actin stress fiber formation. Z-DEVD, L-AA and caspase-3 siRNA significantly attenuated OGD-R-induced hyperpermeability (p < 0.05) while only L-AA decreased cytochrome c levels. Z-DEVD and L-AA protected TJ integrity and actin cytoskeletal assembly. CONCLUSIONS: These results suggest that OGD-R-induced hyperpermeability is ROS and caspase-3 dependent and can be regulated by their inhibitors.


Assuntos
Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Caspase 3/metabolismo , Células Endoteliais/metabolismo , Glucose/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/fisiopatologia , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Edema Encefálico/fisiopatologia , Hipóxia Celular , Células Cultivadas , Ratos , Ratos Sprague-Dawley
20.
Clin Pediatr (Phila) ; 51(5): 447-53, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22199177

RESUMO

OBJECTIVE: To evaluate reliability of umbilical cord blood (UCB) for complete blood count (CBC) and blood cultures compared with the infant's blood from peripheral site for group B streptococcal (GBS) sepsis screening. METHODS: A total of 200 neonates, at risk for GBS infection, were studied prospectively. After birth, UCB sample was obtained for CBC and blood cultures from umbilical vein. Peripheral arterial/venous blood was obtained from the neonate. RESULTS: In 200 neonates, CBC counts were similar for clinical significance except for leukopenia (6% in UCB vs 1.2% in peripheral blood, P = .02). One UCB sample grew GBS and another grew microaerophilic streptococcus, a contaminant. A neonatal sample grew Escherichia coli, a pathogen and another neonatal sample grew Staphylococcus auricularis, a contaminant. CONCLUSION: CBC results were similar from UCB and the infant for the purpose of GBS screening. Contamination of UCB sample for culture is uncommon. Hence, UCB may be used for GBS sepsis screen.


Assuntos
Sangue Fetal/microbiologia , Triagem Neonatal/métodos , Sepse/diagnóstico , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Contagem de Células Sanguíneas , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/sangue , Doenças do Prematuro/diagnóstico , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sepse/sangue , Sepse/microbiologia , Infecções Estreptocócicas/sangue
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