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1.
Hypertens Pregnancy ; 41(2): 139-148, 2022 May.
Article in English | MEDLINE | ID: mdl-35400286

ABSTRACT

OBJECTIVES: Preeclampsia (PE) is an important syndrome of gestation characterized by placental and systemic inflammation. High plasma concentration of uric acid are frequently associated with inflammation and endothelial dysfunction and may contribute to PE pathogenesis. This study aimed to evaluate the vitamin D (VD) immunomodulatory effect on the NLRP1/NLRP3 inflammasomes in placental explants from preeclamptic (PE) and normotensive (NT) pregnant women. STUDY DESIGN: Placental explants from 10 late-onset PE (LOPE), 10 early-onset PE (EOPE), and 10 NT pregnant women were cultured with or without monosodium urate (MSU) and VD. MAIN OUTCOME MEASURES: Gene and protein expression of NLRP1, NLRP3, HMGB1, caspase-1, interleukin-1 beta (IL-1ß), and IL-18 were determined by quantitative PCR and Western blotting/ELISA. Statistical significance was accepted at p < 0.05. RESULTS: Basal gene and protein expression of NLRP1/NLRP3 and IL-1ß, IL-18 and HMGB1 were significantly higher in explants from EOPE compared to LOPE and NT pregnant women. In addition, culture with MSU increased these inflammatory markers, and concomitant treatment with MSU+VD decreased this effect. CONCLUSIONS: The results demonstrated that NLRP1 and NLRP3 inflammasomes are upregulated in the placental tissue of EOPE women, associated with high production of inflammatory cytokines. The in vitro treatment with VD downregulated placental inflammasomes induced by MSU, suggesting its immunomodulatory role in the systemic inflammation of PE.


Subject(s)
HMGB1 Protein , Pre-Eclampsia , Female , Humans , Inflammasomes/genetics , Inflammasomes/metabolism , Inflammation , Interleukin-18 , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Placenta/metabolism , Pregnancy , Uric Acid/pharmacology , Vitamin D , Vitamins
2.
Rev Bras Ginecol Obstet ; 43(1): 61-65, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33513638

ABSTRACT

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.


A Pré-eclâmpsia (PE) é uma doença grave que acomete ∼ 8% das gestações e representa importante causa de morbimortalidade, tanto materna quanto perinatal. O rastreamento da doença é motivo de estudos, porém a complexidade e as incertezas quanto a sua etiologia tornam esse objetivo bastante difícil. Além disso, os custos relacionados com o rastreamento, a heterogeneidade das populações mais afetadas e ainda a falta de métodos de prevenção de grande eficácia reduzem o potencial dos algoritmos de rastreamento. Assim, a Comissão Nacional Especializada sobre Hipertensão na Gravidez da Federação Brasileira das Associações de Ginecologia e Obstetrícia (CNE Hipertensão na Gravidez da FEBRASGO) considera que não há algoritmos de rastreamento que possam ser aplicados no país nesse momento e defende a utilização dos métodos de prevenção como ácido acetilsalicílico e cálcio de maneira ampla.


Subject(s)
Pre-Eclampsia/diagnosis , Prenatal Diagnosis , Brazil , Developing Countries , Female , Humans , Practice Guidelines as Topic , Pregnancy
3.
Rev Bras Ginecol Obstet ; 41(5): 318-332, 2019 May.
Article in English | MEDLINE | ID: mdl-31181585

ABSTRACT

Pre-eclampsia is a multifactorial and multisystemic disease specific to gestation. It is classically diagnosed by the presence of hypertension associated with proteinuria manifested in a previously normotensive pregnant woman after the 20th week of gestation. Pre-eclampsia is also considered in the absence of proteinuria if there is target organ damage. The present review takes a general approach focused on aspects of practical interest in the clinical and obstetric care of these women. Thus, it explores the still unknown etiology, current aspects of pathophysiology and of the diagnosis, the approach to disease prediction, its adverse outcomes and prevention. Management is based on general principles, on nonpharmacological and on pharmacological clinical treatment of severe or nonsevere situations with emphasis on the hypertensive crisis and eclampsia. Obstetric management is based on preeclampsia without or with signs of clinical and/or laboratory deterioration, stratification of gestational age in < 24 weeks, between 24 and less than 34 weeks, and ≥ 34 weeks of gestation, and guidance on route of delivery. An immediate puerperium approach and repercussions in the future life of pregnant women who develop preeclampsia is also presented.


A pré-eclâmpsia é uma doença multifatorial e multissistêmica específica da gestação. É classicamente diagnosticada pela presença de hipertensão arterial associada à proteinúria em gestante previamente normotensa após a 20a semana de gestação. A pré-eclâmpsia também é considerada na ausência de proteinúria se houver lesão de órgão-alvo. A presente revisão tem uma abordagem geral focada em aspectos de interesse prático na assistência clínica e obstétrica dessas mulheres. Assim, explora a etiologia ainda desconhecida, aspectos atuais da fisiopatologia e do diagnóstico e diagnóstico diferencial de convulsões, a abordagem da predição da doença, seus resultados adversos e prevenção. A conduta baseia-se em princípios gerais, tratamento clínico não farmacológico e farmacológico de situações graves ou não graves, com ênfase na crise hipertensiva e eclâmpsia. O controle obstétrico se fundamenta na pré-eclâmpsia sem ou com sinais de deterioração clínica e/ou laboratorial, estratificação da idade gestacional abaixo de 24 semanas, entre 24 e menos de 34 semanas e 34 ou mais semanas de gestação e orientação na via de parto. Uma abordagem imediata do puerpério e repercussões na vida futura de gestantes que desenvolvem pré-eclâmpsia também foram apresentadas.


Subject(s)
Practice Guidelines as Topic , Pre-Eclampsia/prevention & control , Prenatal Care , Female , Humans , Pregnancy
4.
Femina ; 47(5): 258-273, 31 maio 2019. ilus, tab
Article in Portuguese | LILACS | ID: biblio-1046517

ABSTRACT

A pré-eclâmpsia é uma doença multifatorial e multissistêmica específica da gestação. É classicamente diagnosticada pela presença de hipertensão arterial associada à proteinúria em gestante previamente normotensa após a 20a semana de gestação. A pré-eclâmpsia também é considerada na ausência de proteinúria se houver lesão de órgão-alvo. A presente revisão tem uma abordagem geral focada em aspectos de interesse prático na assistência clínica e obstétrica dessas mulheres. Assim, explora a etiologia ainda desconhecida, aspectos atuais da fisiopatologia e do diagnóstico e diagnóstico diferencial de convulsões, a abordagem da predição da doença, seus resultados adversos e prevenção. A conduta baseia-se em princípios gerais, tratamento clínico não farmacológico e farmacológico de situações graves ou não graves, com ênfase na crise hipertensiva e eclâmpsia. O controle obstétrico se fundamenta na pré-eclâmpsia sem ou com sinais de deterioração clínica e/ou laboratorial, estratificação da idade gestacional abaixo de 24 semanas, entre 24 e menos de 34 semanas e 34 ou mais semanas de gestação e orientação na via de parto. Uma abordagem imediata do puerpério e repercussões na vida futura de gestantes que desenvolvem pré-eclâmpsia também foram apresentadas.(AU)


Pre-eclampsia is a multifactorial and multisystemic disease specific to gestation. It is classically diagnosed by the presence of hypertension associated with proteinuria manifested in a previously normotensive pregnant woman after the 20th week of gestation. Pre-eclampsia is also considered in the absence of proteinuria if there is target organ damage. The present review takes a general approach focused on aspects of practical interest in the clinical and obstetric care of these women. Thus, it explores the still unknown etiology, current aspects of pathophysiology and of the diagnosis, the approach to disease prediction, its adverse outcomes and prevention. Management is based on general principles, on nonpharmacological and on pharmacological clinical treatment of severe or nonsevere situations with emphasis on the hypertensive crisis and eclampsia. Obstetric management is based on preeclampsia without or with signs of clinical and/or laboratory deterioration, stratification of gestational age in < 24 weeks, between 24 and less than 34 weeks, and ≥ 34 weeks of gestation, and guidance on route of delivery. An immediate puerperium approach and repercussions in the future life of pregnant women who develop preeclampsia is also presented.(AU)


Subject(s)
Humans , Female , Pregnancy , Pre-Eclampsia/diagnosis , Pre-Eclampsia/etiology , Pre-Eclampsia/prevention & control , Hypertension, Pregnancy-Induced , Eclampsia , Hypertension , Pregnancy Complications , Proteinuria , Seizures , Practice Patterns, Physicians' , Antihypertensive Agents/therapeutic use
6.
Gynecol Obstet Invest ; 83(1): 1-8, 2018.
Article in English | MEDLINE | ID: mdl-28359059

ABSTRACT

BACKGROUND AND AIMS: The inflammatory response in preterm parturition is regulated by the innate immune system. Toll-like receptors (TLR)-2 and TLR-4 are innate immune receptors that recognize the microorganisms most frequently involved in amniotic cavity infections, which are associated with activating the inflammatory response at the maternal-fetal interface during preterm labor. This study aimed to evaluate the expression of TLR-2 and TLR-4 in maternal neutrophils in preterm labor. METHODS: A cross-sectional study was conducted in the Obstetrics Care Unit of Botucatu Medical School, UNESP, Brazil. The preterm group was composed of 20 pregnant women who presented preterm labor and preterm delivery. The control group was composed of 20 nonlaboring pregnant women matched to the preterm group by gestational age. Neutrophils were isolated from peripheral blood and TLR expressions were performed by real-time polymerase chain reaction and flow cytometry. RESULTS: Gene expressions of TLR-2 and TLR-4 in neutrophils from the preterm group were statistically higher than expressions in neutrophils from the matched control group. The percentage of TLR-4+ neutrophils was higher in the preterm group than the matched control group, while the percentage of TLR-2+ neutrophils did not differ between groups. CONCLUSION: TLR-4 expression in maternal neutrophils is associated with spontaneous preterm labor.


Subject(s)
Neutrophils/metabolism , Obstetric Labor, Premature/metabolism , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Adult , Brazil , Cross-Sectional Studies , Female , Gene Expression , Gestational Age , Humans , Infant, Newborn , Pregnancy , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Young Adult
7.
Rio de Janeiro; Guanabara Koogan; 2017. 703 p. ilus..
Monography in Portuguese | LILACS, Coleciona SUS, Sec. Munic. Saúde SP, CACHOEIRINHA-Acervo | ID: biblio-1401072

ABSTRACT

Elaborada com texto claro e objetivo, Obstetrícia não pretende ser um tratado, mas sim, servir como um guia prático para todos aqueles que se iniciam na especialidade, principalmente médicos residentes e alunos de internato. Esta obra tem como plataforma principal e fonte inspiradora o compartilhamento da ampla experiência acumulada ao longo de nossas atividades na Maternidade Escola de Vila Nova Cachoerinha, cujo corpo clínico conjuga competência técnica notável e postura emblemática que resulta na prática obstétrica em sua melhor dimensão. Ao relacionar os itens que compõem a obra, procuramos selecionar temas que são enfrentados na rotina de enfermarias e na assistência ao parto de todos serviços obstetrícia. Buscamos também incluir tópico que atendessem às demandas específicas de cada região brasileira, tornando este livro útil em todo o território nacional. Na seleção dos diversos colaboradores, priorizou-se a experiência acumulada na prática obstétrica real, associada ao convívio diuturno com médicos em formação e especialização... (AU)


Subject(s)
Obstetrics
8.
J Bras Nefrol ; 36(3): 410-3, 2014.
Article in English | MEDLINE | ID: mdl-25317627

ABSTRACT

INTRODUCTION: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. CASE REPORT: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. DISCUSSION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. CONCLUSION: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.


Subject(s)
Abnormalities, Drug-Induced/diagnostic imaging , Abnormalities, Drug-Induced/etiology , Angiotensin II Type 1 Receptor Blockers/adverse effects , Losartan/adverse effects , Ultrasonography, Prenatal , Adult , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Female , Humans , Hypertension/drug therapy , Losartan/therapeutic use , Pregnancy , Pregnancy Complications, Cardiovascular/drug therapy
9.
J. bras. nefrol ; 36(3): 410-413, Jul-Sep/2014. graf
Article in English | LILACS | ID: lil-725489

ABSTRACT

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .


Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...


Subject(s)
Adult , Female , Humans , Pregnancy , Abnormalities, Drug-Induced/etiology , Abnormalities, Drug-Induced , Angiotensin II Type 1 Receptor Blockers/adverse effects , Losartan/adverse effects , Ultrasonography, Prenatal , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Hypertension/drug therapy , Losartan/therapeutic use , Pregnancy Complications, Cardiovascular/drug therapy
10.
Am J Reprod Immunol ; 72(1): 45-56, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24702758

ABSTRACT

PROBLEM: Immunosuppressive drugs change gestational IDO activity at the maternal-fetal interface. METHOD OF STUDY: Analysis of placental IDO expression and activity, interferon gamma (IFN-γ), and IL-10 expression and NFkB activity in renal transplant recipient women under immunosuppressive treatment. RESULTS: We demonstrated a significant reduction in IDO activity (P = 0.0275) and expression (P = 0.026) and in NFkB activity (P = 0.0176) in the villous region of renal transplanted mother. These findings did not correlate with the higher serum levels of kynurenine (P = 0.002). In the decidual compartment, IDO was immunolocalized mainly on the extravillous cytotrophoblast but did not show significant differences among the experimental groups; kynurenine was significantly higher (P = 0.036) and was inversely proportional to the decidual IFN-γ profile (P = 0.0433). No change was seen in IL-10 levels. NFkB activity was significantly higher in decidual compartment correlating with the higher IDO activity and suggesting that in immunosuppressant pregnancy, IDO activity and expression remain regulated by NFkB. CONCLUSION: The increased IDO activity in decidua may indicate an attempt to offset the low expression. These findings call attention to the relevance of IDO activity at the maternal interface in pregnant transplant recipients, likely modulated by immunosuppressive agents and associated with a high risk of associated gestational disorders.


Subject(s)
Immunocompromised Host , Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis , Kidney Transplantation , Placenta/metabolism , Pregnancy Complications/immunology , Adult , Chromatography, High Pressure Liquid , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Interferon-gamma/biosynthesis , NF-kappa B/biosynthesis , Placenta/immunology , Pregnancy
11.
J Obstet Gynaecol Res ; 39(9): 1374-82, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23822541

ABSTRACT

AIM: The aim of this study was to evaluate the passage of fetal erythrocytes into the maternal circulation after invasive obstetric procedures, using the Kleihauer-Betke test, flow cytometry and α-fetoprotein concentration in maternal blood. MATERIAL AND METHODS: This was a prospective descriptive study on patients who underwent: amniocentesis, cordocentesis, chorionic villus sample, amniotic infusion, bladder drainage and ventricular-amniotic shunt to investigate the karyotype; treatment for hydrocephalus, oligohydramnios, obstructive uropathy and polyhydramnios; and investigation of lung maturity. Maternal blood samples were collected before and 60 min after the invasive obstetric procedure in order to evaluate the passage of fetal erythrocytes using the Kleihauer-Betke test, flow cytometry and α-fetoprotein concentration. RESULTS: In total, 43 invasive obstetric procedures were performed. The procedures performed were: 27 cases of amniocentesis (62.7%), seven cases of cordocentesis (16.2%), four chorionic villus samples (9.4%), two amniotic infusions (4.7%), two ventricular-amniotic shunts and one bladder drainage (2.3%). After one case of cordocentesis with two puncture attempts via the placenta, a significant increase in fetal erythrocytes was detected using the three methods. After another cordocentesis with one puncture via the placenta, a significant increase in fetal erythrocytes was detected using flow cytometry and α-fetoprotein concentration, but not through the Kleihauer-Betke test. The other 41 samples did not show any significant increase in fetal erythrocytes in the maternal blood. CONCLUSION: Invasive obstetric procedures performed during prenatal care are safe when performed by experienced professionals with the proper technique, with minimal chance of passage of fetal erythrocytes into the maternal compartment.


Subject(s)
Amniocentesis/adverse effects , Chorionic Villi Sampling/adverse effects , Cordocentesis/adverse effects , Fetal Diseases/diagnosis , Fetomaternal Transfusion/etiology , Maternal-Fetal Exchange , Pregnancy Complications/diagnosis , Adolescent , Adult , Erythrocytes , Female , Fetal Diseases/blood , Fetomaternal Transfusion/blood , Humans , Pregnancy , Pregnancy Complications/blood , Prospective Studies , Young Adult
12.
J Matern Fetal Neonatal Med ; 26(15): 1468-73, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23514270

ABSTRACT

OBJECTIVE: We evaluated whether chronic exposure to immunosuppression in transplant recipients modulate the placental inflammatory cytokine levels associated to gestational tolerance mechanisms. METHODS: Serum samples were collected from 12 renal transplanted pregnant under immunosuppressive regimen treatment and 10 healthy women in second/third trimester of gestation. Term placental tissues (decidua and chorionic villi) were also obtained after elective caesarean. Serum IL-1ß, IL-6, IL-8, IL-12p70 and TNF-α were measured, as also in placental homogenates, by Cytometric Bead Array (CBA) combined with flow cytometry and, TGF-ß and IL-18 were measured by ELISA. RESULTS: Serum levels of IL-6 (p = 0.0001) and TNF-α (0.0112) were higher in the 2nd and 3rd trimesters and in decidua the spectrum of increased pro inflammatory cytokines was wider: IL-1ß (p = 0.0001), IL-6 (p = 0.0001), IL-8 (p = 0.0001), IL-12p70 (p = 0.0001), TGF-ß (p = 0.0089) and TNF-α (p = 0.0002). TGF-ß1 was particularly increased in decidual compartment (p = 0.001). In the chorionic villous, pro inflammatory profile also were maintained. High IL-1ß (p = 0.0001), IL-6 (p = 0.0001), IL-8 (p = 0.0001) and TNF-α (p = 0.0001) levels establish a similar pattern to that seem in decidua. CONCLUSION: Immunosuppressors may impair the immune response, but when associated with pregnancy the cytokine levels seems to shift a proinflammatory profile in placental compartments, which might also impact on the gestational outcomes in transplanted mothers.


Subject(s)
Cytokines/analysis , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Placenta/chemistry , Pregnancy Complications/blood , Cytokines/blood , Decidua/chemistry , Female , Humans , Interleukin-18/analysis , Interleukin-1beta/analysis , Interleukin-6/analysis , Interleukin-6/blood , Interleukin-8/analysis , Interleukin-8/blood , Pregnancy , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/blood
14.
Rev. bras. ginecol. obstet ; 32(12): 609-616, dez. 2010. ilus, graf
Article in Portuguese | LILACS | ID: lil-581578

ABSTRACT

Pré-eclâmpsia é uma síndrome sistêmica caracterizada por intenso estado inflamatório e antiangiogênico. A fisiopatologia da pré-clâmpsia envolve alterações no processo de invasão trofoblástica, com consequente inadequado suprimento sanguíneo uterino e estresse oxidativo do tecido placentário. As alterações placentárias decorrentes desse processo levam à maior produção de sFlt-1, um receptor solúvel para as moléculas de VEGF e PlGF. O sFlt-1 impede com que VEGF e PlGF realizem suas funções na homeostase endotelial, culminando com disfunção dessas células. De uma maneira geral, os processos inflamatórios, de disfunção endotelial e estresse oxidativo estão interligados e agem de maneira sinérgica. Trabalhos recentes têm demonstrado que elevações nas concentrações séricas de sFlt-1 ocorrem 5 a 6 semanas antes das manifestações clínicas da pré-eclâmpsia. Concomitantemente, observa-se queda nas concentrações séricas de PlGF. Sendo assim, as dosagens séricas de sFlt-1 e PlGF têm sido sugeridas para o diagnóstico precoce de pré-eclâmpsia. Ademais, os conhecimentos adquiridos a respeito dos fatores antiangiogênicos proporcionam ainda a possibilidade de novas linhas de pesquisa sobre possíveis terapias para a pré-eclâmpsia. Neste artigo, foram revisados os aspectos inflamatórios e antiangiogênicos envolvidos na fisiopatologia da pré-eclâmpsia. Por fim, foram correlacionados esses aspectos com o risco elevado para doenças cardiovasculares apresentado por essas pacientes ao longo de suas vidas.


Preeclampsia is a systemic syndrome characterized by inflammatory and antiangiogenic states. The pathogenesis of preeclampsia involves deficient trophoblast invasion that is responsible for altered uterine blood flow and placental oxidative stress. The damaged placenta produces higher concentrations of sFlt-1, a soluble receptor for VEGF and PlGF that is released in the maternal circulation and is involved in endothelial dysfunction. Actually, all processes involved in inflammation, endothelial dysfunction and oxidative stress are strongly correlated and act in a synergistic way. Recent data have shown that an increase in serum concentrations of sFlt-1 initiates 5 to 6 weeks before the clinical manifestations of preeclampsia and these alterations correlate with a decrease in serum concentrations of PlGF. Therefore, both sFlt-1 and PlGF have been suggested to be useful for an early-diagnosis of preeclampsia. The knowledge about the role of antiangiogenic factors in the pathogenesis of preeclampsia has raised the possibility of a therapy involving these factors.In this article we revisited the pathogenesis of preeclampsia addressing its antiangiogenic and inflammatory states.In conclusion, we correlated these alterations with the higher risk for cardiovascular diseases presented by these women in future life.


Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Endothelium, Vascular/physiopathology , Inflammation/complications , Oxidative Stress , Pre-Eclampsia/etiology , Pregnancy Outcome
15.
Rev Bras Ginecol Obstet ; 32(12): 609-16, 2010 Dec.
Article in Portuguese | MEDLINE | ID: mdl-21484030

ABSTRACT

Preeclampsia is a systemic syndrome characterized by inflammatory and antiangiogenic states. The pathogenesis of preeclampsia involves deficient trophoblast invasion that is responsible for altered uterine blood flow and placental oxidative stress. The damaged placenta produces higher concentrations of sFlt-1, a soluble receptor for VEGF and PlGF that is released in the maternal circulation and is involved in endothelial dysfunction. Actually, all processes involved in inflammation, endothelial dysfunction and oxidative stress are strongly correlated and act in a synergistic way. Recent data have shown that an increase in serum concentrations of sFlt-1 initiates 5 to 6 weeks before the clinical manifestations of preeclampsia and these alterations correlate with a decrease in serum concentrations of PlGF. Therefore, both sFlt-1 and PlGF have been suggested to be useful for an early-diagnosis of preeclampsia. The knowledge about the role of antiangiogenic factors in the pathogenesis of preeclampsia has raised the possibility of a therapy involving these factors.In this article we revisited the pathogenesis of preeclampsia addressing its antiangiogenic and inflammatory states.In conclusion, we correlated these alterations with the higher risk for cardiovascular diseases presented by these women in future life.


Subject(s)
Endothelium, Vascular/physiopathology , Inflammation/complications , Oxidative Stress , Pre-Eclampsia/etiology , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome
16.
Salud(i)ciencia (Impresa) ; 16(3): 304-307, ago. 2008.
Article in Portuguese | LILACS | ID: biblio-836550

ABSTRACT

Pacientes com insuficiência renal crônica são frequentemente inférteis e a taxa (tasa) de gravidez gira em torno de 1:200. Perda da libido, disfunção ovariana, amenorréia e elevados níveis de prolactina contribuem para a infertilidade. Após (luego) o transplante, entretanto,a fertilidade pode retornar rapidamente e a as taxas de gravidez passam (alcanzan) para 1:50. Não há dúvidas de que essas mulheres constituem um grupo de alto risco e de elevadas taxas de problemas tanto maternos quanto perinatais. Desde a primeira gravidez de sucesso em uma portadora de transplante renal relatada em 1963, diversas publicações têm focado maiores incidências de síndromes hipertensivas, anemia, perda da função renal, pré-eclâmpsia, prematuridade, ruptura prematura de membranas, restrição de crescimento fetal e óbito perinatal. Nosso grupo, na Universidade Federal de SãoPaulo - Brasil tem acumulado experiência nesses casos en este trabalho relatamos nossa experiência comparando com os dados obtidos na literatura. Nós enfatizamos que somente o acompanhamento multiprofissional levará aos melhores resultados. Por fim, gostaríamos de manifestar o nosso desejo (deseo) de entrar em contato com outros grupos para discussão desses (de estos) casos e então aprendermos juntos.


Patients with chronic renal insufficiency are frequentlyinfertile and the incidence of pregnancy is 1:200. Loss oflibido, ovarian dysfunction, anovulatory vaginal bleeding, amenorrhea and high prolactin levels, all contribute to thisinfertility. However, after renal transplantation fertility canreturn rapidly with the chances of pregnancy increasingto about 1:50. There is no doubt that these women are aspecial high risk group with the potential for both maternaland perinatal problems. Since the first successfulpregnancy was reported in 1963 many other publication shave emphasized the increased incidence of hypertension,anaemia, renal function deterioration, pre-eclampsia,preterm delivery, preterm rupture of membranes, fetal growth restriction and stillbirths. At the Federal University of Sao Paulo - Brazil, we have emphasized that a multidisciplinary team approach is essential for their careand in this article we document and analyze the lessonslearnt from our significant single centre experience. We would be happy in contacting other groups of specialists interested in this special group of patients to exchangepoints of view and learn together.


Subject(s)
Kidney Transplantation , Pregnancy , Renal Insufficiency, Chronic , Anemia , Eclampsia , Infant, Premature
17.
Rev. bras. ginecol. obstet ; 27(6): 316-322, jun. 2005. tab
Article in Portuguese | LILACS | ID: lil-417444

ABSTRACT

OBJETIVO: avaliar as inter-relações recíprocas entre o transplante renal e a gravidez por meio da análise das intercorrências clínicas e obstétricas, bem como da investigação do desfecho perinatal. MÉTODOS: foi analisada série retrospectiva de 39 casos de gestação em 37 portadoras de transplante renal no período de janeiro de 1997 a dezembro de 2003. Foi criado um grupo controle composto por 66 grávidas sem doenças clínicas prévias, que freqüentaram pré-natal e deram à luz em 2002 e 2003. Esse grupo foi utilizado para possíveis comparações para as variáveis pré-eclâmpsia, ruptura prematura de membranas, prematuridade e crescimento intra-uterino restrito. Como características demográficas dos dois grupos foram relatados média de idade no momento da concepção, raça e os antecedentes obstétricos. Quanto às características do transplante relatamos o tipo de doador e o esquema imunossupressor utilizado. As variáveis clínicas estudadas foram hipertensão arterial crônica, anemia e infecção do trato urinário. As variáveis relativas ao transplante foram o intervalo entre a cirurgia e a concepção, a ocorrência de disfunção, rejeição e perda do enxerto. Quanto às variáveis obstétricas, analisamos a via de parto, a incidência de pré-eclâmpsia e a ruptura prematura de membranas. Entre os resultados perinatais consideramos a incidência de prematuridade e crescimento intra-uterino restrito. Relacionamos estes resultados aos níveis de creatinina das transplantadas renais no início do pré-natal. Para avaliação estatística foram utilizados os testes de chi2 e exato de Fisher. Em todos os casos, o nível de rejeição para a hipótese de nulidade foi sempre fixado em valor menor ou igual a 0,05 (5 por cento). RESULTADOS: a média de idade das pacientes no momento da concepção foi de 27 anos. O doador vivo foi o tipo mais freqüente. Entre as drogas imunossupressoras, a ciclosporina foi a mais utilizada. Hipertensão arterial crônica foi observada em 82 por cento dos casos, anemia em 77 por cento e infecção do trato urinário em 38,5 por cento. A incidência de disfunção do enxerto foi de 47,4 por cento, tendo sido a pré-eclampsia a sua principal causa. Perda do transplante ocorreu em 10,2 por cento dos casos...


Subject(s)
Humans , Female , Pregnancy , Adult , Hypertension , Immunosuppression Therapy , Kidney Transplantation , Perinatal Care , Pre-Eclampsia , Pregnancy, High-Risk
18.
Femina ; 32(10): 865-869, nov.-dez. 2004. ilus
Article in Portuguese | LILACS | ID: lil-403073

ABSTRACT

A Importância das alterações glomerulares na pré-eclâmpsia é indiscutível e seu estudo possui evolução histórica. A primeira e mais significativa lesão descrita foi a endoteliose capilar glomerular, relatada a princípio como sendo patognomônica da doença. Entretanto com a realização mais freqüente de biópsias renais foi possível a identificação dessa lesão em outras patologias e até mesmo em gestantes normais, o que implicou nos dias atuais no abandono do termo patognomônica. Além disso, outras alterações bem como suas relações com graus variáveis da doença foram identificadas. Uma das mais importantes é a glomeruloesclerose segmentar focal, que se relaciona com casos mais graves de pré-eclâmpsia e demora no retorno à normalidade após o parto. O estudo das alterações glomerulares serviu ainda para mostrar aspectos comuns entre pré-eclâmpsia e doenças de origem imunológica, o que fortalece a teoria de estar essa também relacionada à ativação do sistema imune


Subject(s)
Humans , Female , Glomerulosclerosis, Focal Segmental , Immune System , Pre-Eclampsia , Biopsy , Glomerulonephritis
19.
Femina ; 32(2): 111-115, mar. 2004. tab
Article in Portuguese | LILACS | ID: lil-395908

ABSTRACT

O transplante renal representa importante tratamento para portadoras de doença renal em fase terminal. Os progressos obtidos nas técnicas dos transplantes possibilitam cada vez mais a ocorrência do binômio transplante renal e gravidez. Intercorrências clínicas e obstétricas podem ser responsáveis pelo comprometimento da função do enxerto, que juntamente com as drogas imunossupressoras representam situação especial. São observadas maiores incidências de síndromes hipertensivas, anemia e processos infecciosos. Rotura prematura de membranas se associa ao estado imunológico dessas pacientes. Os resultados perinatais mostram indicência elevada de prematuridade e recém-nascidos pequenos para idade gestacional. A via de parto deve obedecer indicação obstétrica e o aleitamento materno é contra-indicado quando da utilização de drogas imunossupressoras. Lembramos ainda que acidentes durante o ato operatório ou hipotensão materna podem resultar em grave comprometimento da função do enxerto


Subject(s)
Humans , Female , Immunosuppressive Agents , Kidney Transplantation , Pregnancy , Azathioprine , Cyclosporine , Prednisone , Pregnancy Complications
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