RESUMO
Many conditions may impair or delay language development, including socioeconomic status, parent's education, or intrauterine environment. Accordingly, increasing evidence has described that pregnancy complications, including gestational diabetes mellitus (GDM), preeclampsia, and preterm delivery, are associated with the offspring's impaired neurodevelopment. Since language is one of the high brain functions, alterations in this function are another sign of neurodevelopment impairment. How these maternal conditions may generate language impairment has yet to be entirely understood. However, since language development requires adequate structural formation and function/connectivity of the brain, these processes must be affected by alterations in maternal conditions. However, the underlying mechanisms of these structural alterations are largely unknown. This manuscript critically analyzes the literature focused on the risk of developing language impairment in children of mothers with GDM, preeclampsia, and preterm delivery. Furthermore, we highlight potential underlying molecular mechanisms associated with these alterations, such as neuroinflammatory and metabolic and cerebrovascular alterations.
Assuntos
Diabetes Gestacional , Transtornos do Desenvolvimento da Linguagem , Pré-Eclâmpsia , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Criança , MãesRESUMO
Disruption of the blood-brain barrier (BBB) is central in the pathophysiology of acute cerebral complications in women who have preeclampsia. Underling mechanisms are unclear. Using female human brain endothelial cells as an in vitro model of BBB, we show that plasma of women with preeclampsia increases cell apoptosis and permeability via activation of the vascular endothelial growth factor receptor 2 (VEGFR2). Since plasma of women with preeclampsia also enhanced VEGFR2 phosphorylation in the tyrosine 951 but decreased phosphorylation at the tyrosine 1175, we propose the former would be the more likely active form of VEGFR2 responsible for BBB alterations.
Assuntos
Pré-Eclâmpsia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Apoptose , Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Células Endoteliais/metabolismo , Feminino , Humanos , Fosforilação , Pré-Eclâmpsia/metabolismo , Gravidez , Tirosina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND AND PURPOSE: Systemic inflammation conveys information about ischaemic stroke prognosis. Growth factors with neurotrophic and angiogenesis-regulating properties might provide additional information about sequelae. The prognostic performance of circulating vascular endothelial growth factor (VEGF), placental growth factor, interleukin 6 and C-reactive protein measured after acute ischaemic stroke was evaluated. METHODS: Blood samples were collected from n = 45 patients within 24-48 h of acute ischaemic stroke. The primary outcome was death or moderate to severe disability at 6 months (modified Rankin Scale >2). Logistic regression models were used to determine the area under the receiver operating characteristic curve (AUC). Correlation and principal component analyses were performed to examine interrelationships amongst biomarkers. RESULTS: Vascular endothelial growth factor was elevated in ischaemic stroke patients who died or had moderate to severe disability at six months. Correlation analysis revealed interrelationships between VEGF and HbA1c, triglycerides, erythrocyte sedimentation rate and National Institutes of Health Stroke Scale and Rankin scores, whereas principal component analyses identified VEGF as a major loading factor that discriminated good from poor prognosis. There were no significant differences in AUC using each protein individually to identify patients who had modified Rankin Scale score >2 at 6 months (n = 15/41, AUC 0.61-0.74). However, the AUC increased significantly when combining VEGF with interleukin 6 and C-reactive protein compared to the VEGF-only model (AUC 0.92 vs. 0.67, p = 0.02). CONCLUSION: Circulating VEGF was elevated 24-48 h after acute ischaemic stroke and conveyed prognostic information about moderate to severe disability at 6 months.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Fator A de Crescimento do Endotélio Vascular/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Fator de Crescimento Placentário , PrognósticoRESUMO
Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17ß-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERß. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERß receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.
Assuntos
Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Neovascularização Fisiológica/efeitos dos fármacos , Receptor A2A de Adenosina/genética , Ferimentos Penetrantes/genética , Adenosina/análogos & derivados , Adenosina/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação da Expressão Gênica , Pulmão/citologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neovascularização Fisiológica/genética , Fenetilaminas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptor Cross-Talk , Receptor A2A de Adenosina/metabolismo , Fatores Sexuais , Transdução de Sinais , Cicatrização/efeitos dos fármacos , Cicatrização/genética , Ferimentos Penetrantes/tratamento farmacológico , Ferimentos Penetrantes/metabolismo , Ferimentos Penetrantes/patologiaRESUMO
We aim to investigate the role of A2A receptor in peritonitis-related sepsis by injection of a fecal solution (FS) as a model of polymicrobial infection. C57/black J6 wild-type (WT) and A2A-deficient mice (A2AKO) were exposed to sepsis induced by intraperitoneal injection of a FS (FS-induced peritonitis) or instead was injected with saline buffer (Sham). Survival rate and sepsis score were measured up to 48 h. The presence of bacteria in tissue homogenates was analyzed. Telemetry and speckle laser Doppler were used for systemic blood pressure and peripheral blood perfusion analysis, respectively. Histological analysis and identification of active caspase 3 were performed in selected organs, including the liver. The survival rate of A2AKO mice exposed to FS-induced peritonitis was significantly higher, and the sepsis score was lower than their respective WT counterpart. Injection of FS increases (50 to 150 folds) the number of colonies forming units in the liver, kidney, blood, and lung in WT mice, while these effects were significantly attenuated in A2AKO mice exposed to FS-induced peritonitis. A significant reduction in both systolic and diastolic blood pressure, as well as in the peripheral perfusion was observed in WT and A2AKO mice exposed to FS-induced peritonitis. Although, these last effects were significantly attenuated in A2AKO mice. Histological analysis showed a large perivascular infiltration of polymorphonuclear in the liver of WT and A2AKO mice exposed to FS-induced peritonitis, but again, this effect was attenuated in A2AKO mice. Finally, high expression of active caspase 3 was found only in the liver of WT mice exposed to FS-induced peritonitis. The absence of the A2A receptor increases the survival rate in mice exposed to polymicrobial sepsis. This outcome was associated with both hemodynamic compensation and enhanced anti-bacterial response.
Assuntos
Peritonite/metabolismo , Receptor A2A de Adenosina/metabolismo , Sepse/metabolismo , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Peritonite/genética , Peritonite/microbiologia , Peritonite/mortalidade , Receptor A2A de Adenosina/genética , Sepse/genética , Sepse/mortalidade , Taxa de SobrevidaRESUMO
Evidence from clinical studies has proposed that children born from preeclamptic women have a higher risk of suffering neurological, psychological, or behavioral alterations. However, to date, the mechanisms behind these outcomes are poorly understood. Here, we speculate that the neurodevelopmental alterations in the children of preeclamptic pregnancies result from impaired angiogenesis. The pro-angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are key regulators of both vascular and neurological development, and it has been widely demonstrated that umbilical blood of preeclamptic pregnancies contains high levels of soluble VEGF receptor type 1 (sFlt-1), a decoy receptor of VEGF. As a consequence, this anti-angiogenic state could lead to long-lasting neurological outcomes. In this non-systematic review, we propose that alterations in the circulating concentrations of VEGF, PlGF, and sFlt-1 in preeclamptic pregnancies will affect both fetal cerebrovascular function and neurodevelopment, which in turn may cause cognitive alterations in post-natal life.
RESUMO
Placentas from gestational diabetes mellitus (GDM) are often hypervascularized; however, participation of vascular endothelial growth factor (VEGF) and its receptors in this placental adaptation is unclear. We aimed to test whether changes in phosphorylation of tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial growth factor receptor 2 (KDR) are associated with the proangiogenic state observed in placentas from GDM. We obtained placental samples from women with normal pregnancies (n = 24) or GDM (n = 18). We measured the relative expression of markers for endothelial cell number (CD31, CD34), VEGF, vascular endothelial growth factor receptor 1 (Flt-1), KDR, pY951 and pY1175 of KDR in placental homogenate. Immunohistochemistry of placental blood vessels were performed using CD34. Proliferation and migration of human umbilical vein endothelial cells (HUVEC) obtained from normal pregnancy and GDM were determined in absence or presence of conditioned medium (CM) harvested from GDM or normoglycemic HUVEC cultures. GDM was associated with more CD31 and CD34 protein compared to normal pregnancy. High number, but reduced area of placental blood vessels was found in GDM. Reduced Flt-1 levels (mRNA and protein) are associated with reduced KDR mRNA, but higher KDR protein levels in placentas from GDM. No significant changes in Y951-or Y1175-phosphorylation of KDR in placentas from GDM were found. GDM did not alter proliferation of HUVECs, but enhanced migration. Conditioned medium harvested from GDM HUVEC cultures enhanced KDR protein amount, tube formation capacity and cell migration in HUVEC isolated from normoglycemic pregnancies. The data indicate that GDM is associated with reduced expression of Flt-1 but high pro-migratory activation of KDR reflecting a proangiogenic state in GDM.
Assuntos
Movimento Celular , Diabetes Gestacional/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Antígenos CD34/genética , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Células Cultivadas , Diabetes Gestacional/diagnóstico , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Recém-Nascido , Masculino , Placenta/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Gravidez , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/µg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/µg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/µg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/µg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/µg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/µg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/µg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = -0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.
Assuntos
Adenosina/sangue , Obesidade/sangue , Sobrepeso/sangue , Complicações na Gravidez/sangue , Adulto , Índice de Massa Corporal , Estudos Transversais , Dieta , Feminino , Humanos , Gravidez , Aumento de PesoRESUMO
The underlying molecular mechanisms involve in the regulation of the angiogenic process by insulin are not well understood. In this review article, we aim to describe the role of insulin and insulin receptor activation on the control of angiogenesis and how these mechanisms can be deregulated in human diseases. Functional expression of insulin receptors and their signaling pathways has been described on endothelial cells and pericytes, both of the main cells involved in vessel formation and maturation. Consequently, insulin has been shown to regulate endothelial cell migration, proliferation, and in vitro tubular structure formation through binding to its receptors and activation of intracellular phosphorylation cascades. Furthermore, insulin-mediated pro-angiogenic state is potentiated by generation of vascular growth factors, such as the vascular endothelial growth factor, produced by endothelial cells. Additionally, diseases such as insulin resistance, obesity, diabetes, and cancer may be associated with the deregulation of insulin-mediated angiogenesis. Despite this knowledge, the underlying molecular mechanisms need to be elucidated in order to provide new insights into the role of insulin on angiogenesis.
RESUMO
We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular endothelial growth factor (VEGF) expression is impaired in feto-placental endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein endothelial cells (HUVECs) and human placental microvascular endothelial cells (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using small interference RNA (siRNA) for A2A were performed, and transfected cells were used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell proliferation and angiogenesis in vitro. CGS-21680 (A2A agonist, 24 h) increases HUVEC and hPMEC proliferation in a dose response manner. Furthermore, similar to CGS-21680, the nitric oxide donor, S-nitroso-N-acetyl-penicillamine oxide (SNAP), increased cell proliferation in a dose response manner (logEC50 10-9.2 M). In hPMEC, CGS-21680 increased VEGF protein levels in both normal (â¼1.5-fold) and pre-eclamptic pregnancies (â¼1.2-fold), an effect blocked by the A2A antagonist, ZM-241385 (10-5 M) and the inhibitor of NO synthase, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Subsequently, SNAP partially recovered cell proliferation and in vitro angiogenesis capacity of cells from normal pregnancies exposed to siRNA for A2A. CGS-21680 also increased (â¼1.5-fold) the level of VEGF mRNA in HUVEC from normal pregnancies, but not in pre-eclampsia. Additionally, transfection with siRNA for A2A decrease (â¼30 %) the level of mRNA for VEGF in normal pregnancy compared to untransfected cells, an effect partially reversed by co-incubation with SNAP. The A2A-NO-VEGF pathway is present in endothelium from microcirculation and macrocirculation in both normal and pre-eclamptic pregnancies. However, NO signaling pathway seems to be impaired in HUVEC from pre-eclampsia.
Assuntos
Endotélio Vascular/metabolismo , Pré-Eclâmpsia/metabolismo , Receptor A2A de Adenosina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Óxido Nítrico/metabolismo , Fenetilaminas/farmacologia , Gravidez , Transdução de Sinais/efeitos dos fármacosRESUMO
Preeclampsia is a syndrome characterized by hypertension during pregnancy, which is a leading cause of morbidity and mortality in both mother and newborn in developing countries. Some advances have increased the understanding of pathophysiology of this disease. For example, reduced utero-placental blood flow associated with impaired trophoblast invasion may lead to a hypoxic placenta that releases harmful materials into the maternal and feto-placental circulation and impairs endothelial function. Identification of these harmful materials is one of the hot topics in the literature, since these provide potential biomarkers. Certainty, such knowledge will help us to understand the miscommunication between mother and fetus. In this review we highlight how placental extracellular vesicles and their cargo, such as small RNAs (i.e., microRNAs), might be involved in endothelial dysfunction, and then in the angiogenesis process, during preeclampsia. Currently only a few reports have addressed the potential role of endothelial regulatory miRNA in the impaired angiogenesis in preeclampsia. One of the main limitations in this area is the variability of the analyses performed in the current literature. This includes variability in the size of the particles analyzed, and broad variation in the exosomes considered. The quantity of microRNA targets genes suggest that practically all endothelial cell metabolic functions might be impaired. More studies are required to investigate mechanisms underlying miRNA released from placenta upon endothelial function involved in the angiogenenic process.
RESUMO
To investigate the functionality of A2B adenosine receptor (A2BAR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnancies (n = 15) or pregnancies with preeclampsia (n = 15). Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, the A2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level of A2BAR and logEC50 for NECA-mediated proliferation than normotensive pregnancies. The stimulatory effect of NECA (10 µM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 µM, 24 h) reduced the NECA-induced cell proliferation/migration in HUVEC from normal pregnancy; however in preeclampsia only NECA-induced cell proliferation was reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of VEGF in cells from normal pregnancy and effect prevented by MRS-1754 coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level of A2BAR and impairment of A2BAR-mediated NO/VEGF signaling pathway.
Assuntos
Movimento Celular , Proliferação de Células , Endotélio Vascular/metabolismo , Feto/metabolismo , Pré-Eclâmpsia/metabolismo , Receptor A2B de Adenosina/metabolismo , Acetamidas/farmacologia , Adenosina-5'-(N-etilcarboxamida)/farmacologia , Adulto , Antineoplásicos/farmacologia , Endotélio Vascular/patologia , Feminino , Feto/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxido Nítrico/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Purinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio VascularRESUMO
Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (â¼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study.
Assuntos
Arginina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Suplementos Nutricionais , Hipoglicemiantes/administração & dosagem , Malus , Aloxano , Animais , Arginina/farmacocinética , Disponibilidade Biológica , Glicemia , Células Cultivadas , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Feminino , Alimentos Fortificados , Hipoglicemiantes/farmacocinética , Miócitos de Músculo Liso , RatosRESUMO
To investigate whether fetal endothelial cell proliferation and migration are modulated by the A2A adenosine receptor (A2AAR), nitric oxide (NO) and the vascular endothelial growth factor (VEGF) signaling pathway, we isolated human umbilical vein endothelial cells from normal pregnancy (n = 23), preterm delivery (n = 4), and late-onset (LOPE, n = 10) and early-onset preeclampsia (EOPE, n = 8). We used the non-selective adenosine receptor agonist (NECA) and the selective agonist (CGS-21680) and/or selective antagonist (ZM-241385) for A2AAR. Also, the nitric oxide synthase (NOS) inhibitor, L-NAME, was used in co-incubation with CGS-21680. Compared to normal pregnancy, EOPE exhibited low cell proliferation and migration associated with reduced expressions of A2AAR and VEGF and NO synthesis (i.e., total and phosphorylated serine(1177) endothelial NOS and nitrite formation). In contrast, LOPE exhibited the opposite behavior in all these markers compared to normal pregnancy or EOPE. Cell proliferation and migration were increased by CGS-21680 (or NECA) in all analyzed groups (EOPE>LOPE>normal pregnancy) compared to their respective basal conditions, an effect that was associated with high NO and VEGF synthesis and blocked by ZM-241385 with significantly different IC50 for each group (EOPE>LOPE>normal pregnancy). The differences seem independent of gestational age. L-NAME blocked the CGS-21680-mediated cell proliferation and migration in normal pregnancy and LOPE (IC50 = 36.2 ± 2.5 and 8.6 ± 2.2 nM, respectively) as well as the VEGF expression in normal pregnancy. Therefore, the A2AAR/NO/VEGF signaling pathway exhibits a pro-angiogenic effect in normal pregnancies and LOPE, whereas impairment in this pathway seems related to the reduced angiogenic capacity of the fetal endothelium in EOPE.
Assuntos
Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Pré-Eclâmpsia/metabolismo , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Adenosina/metabolismo , Western Blotting , Movimento Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Feminino , Feto , Humanos , Imuno-Histoquímica , Pré-Eclâmpsia/fisiopatologia , Gravidez , Agonistas do Receptor Purinérgico P1/farmacologia , Antagonistas de Receptores Purinérgicos P1/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Veias UmbilicaisRESUMO
There are no data regarding adenosine levels in obese children, even though is a ubiquitous molecule implicated in the regulation of lipid metabolism in humans. To determinate whether adenosine plasma levels are related with anthropometric and biochemical markers in children, we studied 51 students belong to Ramon Belmar School in Linares, Chile. Review of clinical data and frequent food questionnaire were taken in order to collect the information. Plasma adenosine levels were measured by high-performance liquid chromatography and biochemical parameters including insulin, glucose, total proteins, and lipid profile by using standard colorimetric assays. Children with detectable (above 0.1 µM) adenosine plasma levels (n = 30; BMI, 22.3 ± 0.7) had higher total cholesterol (P < 0.05); triglycerides (P < 0.01) and LDL-cholesterol (P < 0.05) concentrations than children with undetectable adenosine levels (n = 21; BMI, 23.9 ± 0.61). Among the analyzed variables, only BMI and BMI standard deviation score (BMI-SDS) were positively correlated with adenosine levels. Besides, obese children (n = 10) showed significantly high adenosine levels compared to controls (n = 11; 1.8 ± 0.2 vs. 1.2 ± 0.1 µM/mg protein, respectively. P < 0.05), but not compared to overweight children (n = 9). In conclusion, obesity in children is associated to high adenosine plasma levels. This study opens a new perspective to investigate the role of adenosine in the regulation of lipid metabolism in obese children.
Assuntos
Adenosina/sangue , Obesidade/metabolismo , Adolescente , Antropometria , Índice de Massa Corporal , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Triglicerídeos/sangueRESUMO
OBJECTIVE: To investigate whether the February 27th earthquake exposition was associated to adverse perinatal outcomes in Chilean pregnant women. METHODS: We analyzed all deliveries occurred in 2009 (n = 3,609) and 2010 (n = 3,279) in a reference hospital in the area of the earthquake. Furthermore, we investigated pregnant women who gave birth between March 1st and December 31st 2010 (n = 2,553) and we classified them according to timing of exposition. RESULTS: We found a 9% reduction in birth rate, but an increase in the rate of early preterm deliveries (<34 weeks), premature rupture of membranes (PROM), macrosomia, small for gestational age, and intrauterine growth restriction (IUGR) after the earthquake, in contrast to the previous year. Women exposed to the earthquake during her first trimester delivered smaller newborns (3,340 ± 712 g v/s 3,426 ± 576 g respectively, p = 0.007) and were more likely diagnosed with early preterm delivery, preterm delivery (<37 weeks) and PROM but were less likely diagnosed with IUGR and late delivery (42 weeks, p < 0.05) compared to those exposed at third trimester. Accordingly, IUGR and preterm deliveries presented elevated healthcare costs. CONCLUSION: Natural disasters such as earthquakes are associated to adverse perinatal outcomes that impact negatively the entire maternal-neonatal healthcare system.