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1.
Early Hum Dev ; 155: 105323, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33578219

RESUMO

BACKGROUND: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare and fatal disorder that occurs in the developing fetal lungs; at birth, infants exhibit an oxygenation disorder accompanied by severe pulmonary hypertension (PH) and have a very short life span. ACDMPV is definitively diagnosed by pathological findings, and infants born with unexplained severe PH may not be properly diagnosed without a biopsy or autopsy. METHODS: Japanese infants with unexplained severe PH were enrolled in this study. Genetic analyses were performed on DNA extracted from peripheral blood leukocytes. Sanger sequencing or next-generation sequencing was performed by coding exons and introns for FOXF1 in all samples. For individuals without pathogenic exonic variants, multiplex ligation-dependent probe amplification was performed to identify copy number variations (CNVs) in exons, introns, and in the upstream region of FOXF1. RESULTS: This study included 30 infants who were diagnosed over the course of nine years. Four individuals had the pathogenic variations on the exon 1 of FOXF1, including two frameshift and two missense variations. Pathogenic CNVs were found in another five individuals. CONCLUSION: In the pathologically proven ACDMPV patients, the ratios of cases with exonic variations, CNVs, and no genetic findings were reported as 45%, 45% and 10%, respectively. We estimate that about 30% (10 (9 + 1) out of 30) of individuals with unexplained severe PH had ACDMPV.


Assuntos
Hipertensão Pulmonar , Síndrome da Persistência do Padrão de Circulação Fetal , Variações do Número de Cópias de DNA , Fatores de Transcrição Forkhead/genética , Testes Genéticos , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/genética , Incidência , Lactente , Recém-Nascido , Síndrome da Persistência do Padrão de Circulação Fetal/epidemiologia , Síndrome da Persistência do Padrão de Circulação Fetal/genética
2.
BMC Pregnancy Childbirth ; 20(1): 750, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267789

RESUMO

BACKGROUND: This study aimed to compare the echocardiographic changes and cardiac biomarkers between women with singleton and twin pregnancies. METHODS: From April 2014 to March 2016, this longitudinal cohort study invited pregnant women who were scheduled to give birth at Hokkaido University Hospital. We analyzed prospectively collected data on simultaneously determined echocardiographic parameters and blood cardiac markers of 44 women with singleton and 22 women with twin pregnancies. Furthermore, we tested the mixed-effect models for echocardiographic parameters and cardiac biomarkers. RESULTS: During the third trimester and immediately postpartum (within 1 week after childbirth), the mean left atrial volume index and brain natriuretic peptide (BNP) level were significantly higher in women with twin pregnancies than in those with singleton pregnancies. Women with twin pregnancies also had significantly smaller second-trimester inferior vena cava diameters and significantly higher third-trimester creatinine levels than those with singleton pregnancies. BNP positively correlated with the left atrial volume index (ß = 0.49, p < 0.01) and the ratio of early diastolic transmitral to mitral annular velocity (E/e') (ß = 0.41, p < 0.01). At 1 month after childbirth in women with singleton pregnancies, BNP and N-terminal precursor protein BNP (NT-proBNP) fragments immediately postpartum negatively correlated with the later E/e' (r = - 0.33, p = 0.02 and r = - 0.36, p < 0.01, respectively). CONCLUSIONS: The intravascular cardiac load reached maximum within 1 week after childbirth and was greater in women with twin pregnancies than in those with singleton pregnancies. BNP/NT-proBNP significantly positively correlated with LA volume index and E/e'. In women with singleton pregnancies, BNP secreted immediately after childbirth might improve the diastolic functions 1 month after childbirth.


Assuntos
Átrios do Coração/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Gravidez de Gêmeos/sangue , Adulto , Estudos de Casos e Controles , Creatinina/sangue , Ecocardiografia , Feminino , Hemodinâmica , Humanos , Estudos Longitudinais , Gravidez , Disfunção Ventricular Esquerda/etiologia
3.
Open Heart ; 5(2): e000829, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30245837

RESUMO

Objective: Women with hypertensive disorders of pregnancy (HDP) show elevated risk of heart failure despite decreased circulating plasma volume compared with those with normotensive control pregnancies (NCP). This study was performed to better characterise the heart in women with HDP and determine whether high-sensitivity troponin I (hs-TnI) around childbirth predicts reduced left ventricular (LV) relaxation at 1 month postpartum. Methods: Echocardiography was performed longitudinally during the first, second and third trimesters and immediately postpartum within 1 week and 1 month postpartum in 24 women with HDP, with simultaneous determination of blood variables in comparison with 51 women with NCP. Results: Compared with NCP, HDP showed greater antepartum left atrial (LA) volume, LV mass and inferior vena cava (IVC) diameter, higher peripartum brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide and hs-TnI with the highest value immediately postpartum, and lower early diastolic mitral annular velocity (e') during pregnancy/postpartum. In analyses of data on HDP and NCP, hs-TnI at the third trimester as well as that immediately postpartum was negatively correlated with later e' at 1 month postpartum. The areas under the receiver operating characteristic curves were 0.82 and 0.81 for hs-TnI at the third trimester and immediately postpartum, respectively, in the prediction of reduced LV relaxation at 1 month postpartum. Conclusion: Reduced LV diastolic function and decreased splanchnic blood reservoir may contribute to the increased third trimester IVC diameter and LA volume in women with HDP. The rise in hs-TnI around childbirth was associated with poor LV relaxation ability at 1 month postpartum.

4.
Open Heart ; 5(2): e000850, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057771

RESUMO

Objective: This longitudinal study was performed to determine changes in echocardiography parameters in association with various biomarker levels in pregnancy/postpartum. Methods: Fifty-one healthy pregnant women underwent echocardiography with simultaneous determination of blood levels of five biomarkers at each of the first, second and third trimesters of pregnancy, immediately postpartum within 1 week after childbirth and approximately 1 month postpartum. Data on 255 echocardiography scans (five times per woman) and biomarkers were analysed. Results: Left ventricular end-diastolic dimension, left atrial (LA) volume index and left ventricular (LV) mass index increased with advancing gestation and reached the maximum immediately postpartum concomitant with the highest brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI) and creatine kinase MB levels. The inferior vena cava diameter was significantly reduced in the third trimester compared with that in the first trimester and the peak occurred immediately after childbirth. In 255 paired measurements, hs-TnI level was significantly positively correlated with LA volume index and LV mass index; BNP and NT-proBNP were significantly positively correlated with LA volume index and estimated glomerular filtration rate (eGFR) was significantly positively correlated with the average of early diastolic septal and lateral mitral annular velocity (e'). Conclusions: Maximal cardiac changes in morphology occurred postpartum within 1 week after childbirth, not during pregnancy. BNP/NT-proBNP, hs-TnI and eGFR reflected cardiac changes in pregnancy.

5.
Pediatr Res ; 83(2): 477-483, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29569581

RESUMO

BackgroundGenetic variants responsible for childhood interstitial lung disease (chILD) have not been studied extensively in Japanese patients.MethodsThe study population consisted of 62 Japanese chILD patients. Twenty-one and four patients had pulmonary hypertension resistant to treatment (PH) and hypothyroidism, respectively. Analyses of genetic variants were performed in all 62 patients for SFTPC and ABCA3, in all 21 PH patients for FOXF1, and in a limited number of patients for NKX2.1.ResultsCausative genetic variants for chILD were identified in 11 (18%) patients: SFTPC variants in six, NKX2.1 variants in three, and FOXF1 variants in two patients. No patients had ABCA3 variants. All three and two patients with NKX2.1 variants had hypothyroidism and developmental delay, respectively. We found six novel variants in this study.ConclusionMutations in SFTPC, NKX2.1, and FOXF1 were identified among Japanese infants and children with chILD, whereas ABCA3 mutations were rare.


Assuntos
Hipertensão Pulmonar/genética , Hipotireoidismo/genética , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/genética , Transportadores de Cassetes de Ligação de ATP/genética , Criança , Oxigenação por Membrana Extracorpórea , Feminino , Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença , Variação Genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Recém-Nascido , Japão , Masculino , Mutação , Estudos Prospectivos , Proteína C Associada a Surfactante Pulmonar/genética , Fator Nuclear 1 de Tireoide/genética
6.
J Obstet Gynaecol Res ; 43(6): 1008-1013, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28621045

RESUMO

AIM: Urine podocin mRNA expression and urine podocin : nephrin mRNA expression ratio (PNR) increase with increasing proteinuria during pregnancy complicated with pre-eclampsia (PE). This suggests that urine podocytes with reduced nephrin mRNA expression are abundant in pathological podocyturia. The aim of this study was therefore to determine post-partum changes in podocyturia and PNR in relation to proteinuria after pre-eclampsia (PE). METHODS: A total of 137 peripartum urine specimens, consisting of 72 and 65 from 24 and 30 women with PE and normotensive control pregnancies (NCP), respectively, were studied. Determination of urine protein and creatinine concentration and quantitative analysis of podocyte-specific podocin and nephrin mRNA expression were carried out using reverse transcription-polymerase chain reaction in pelleted urine samples. Podocyturia was monitored via urine podocin mRNA expression. Podocyturia and proteinuria were normalized by urine creatinine concentration. RESULTS: Podocyturia and urine PNR decreased with decreasing proteinuria as well as with increasing time after delivery in the urine from PE women. In physiological proteinuria (i.e. protein : creatinine ratio [P/Cr] 0.005-0.1 mg/mg), however, both podocyturia and PNR were significantly greater in the urine from PE women compared with NPC women, although P/Cr was similar between the groups (median, 0.037 mg/mg for PE vs 0.029 mg/mg for NCP). CONCLUSIONS: Podocyturia decreases with decreasing proteinuria in PE women after childbirth. In PE women, however, pathological podocyturia consisting of podocytes with decreased nephrin mRNA expression persisted even after proteinuria decreased to a level similar to that in NCP women.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/urina , Proteínas de Membrana/urina , Podócitos , Período Pós-Parto/urina , Pré-Eclâmpsia/urina , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Urina/citologia , Adulto Jovem
7.
J Obstet Gynaecol Res ; 43(7): 1152-1158, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28422347

RESUMO

AIM: This study was performed to determine the associations between serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels at mid-gestation with the risk of small-for-gestational-age (SGA) neonates born at gestational week (GW) ≥ 36 in healthy women. METHODS: PlGF and sFlt-1 concentrations were determined at GW 24-27 in 183 women with births at GW ≥ 36, but without gestational diabetes mellitus and hypertension. RESULTS: Thirteen (7.1%) SGA neonates were born. Median (range) GW at blood sampling was similar between women with and without SGA (25 [24-25] and 24 [24-27], respectively, P = 0.671). Pre-pregnancy body mass index (BMI) and PlGF levels were significantly lower in women with than without SGA, while sFlt-1 levels and sFlt-1 : PlGF ratio (sFlt-1/PlGF) did not differ significantly between the two groups. PlGF and sFlt-1/PlGF, but not BMI or sFlt-1, showed significant correlations with birthweight z-score; the correlation was positive for PlGF and negative for sFlt-1/PlGF. Women with PlGF level < 10th percentile and those with sFlt-1/PlGF level > 90th percentile showed significantly increased risk of SGA compared to those with respective counterpart characteristics; relative risk was 3.8 (95% confidence interval, 1.3-11.3; 21% [4/19] vs 5.5% [9/164]) for PlGF and 7.9 (95% confidence interval, 3.0-20.8, 33.3% [6/18] vs 4.2% [7/165]) for sFlt-1/PlGF. CONCLUSION: Maternal PlGF and sFlt-1/PlGF determined during GW 24-27 were associated with the risk of SGA neonates born at GW ≥ 36, even in women with uncomplicated pregnancies.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Placentário/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Segundo Trimestre da Gravidez , Adulto Jovem
8.
J Obstet Gynaecol Res ; 43(6): 967-973, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28422372

RESUMO

AIM: Dipstick results for proteinuria are affected by urine concentration, and thus urine creatinine concentration ([Cr]). This study was performed to determine whether spot urine [Cr] changes significantly during pregnancy, leading to a significantly different false-negative rate (FNR) on dipstick test between trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in 631 spot urine samples with negative/equivocal dipstick from 425 pregnant women. False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg. RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3-477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n = 344), and third (n = 191) trimester urine samples, respectively (P = 0.000, Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was 47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining 611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046). CONCLUSIONS: Urine samples in the second and third trimesters were more likely to be diluted compared with the first trimester. This was associated with high FNR in third trimester urine samples.


Assuntos
Creatinina/urina , Trimestres da Gravidez/urina , Adulto , Reações Falso-Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
9.
Am J Physiol Renal Physiol ; 312(6): F1112-F1119, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28274928

RESUMO

Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient (r) = -0.614/-0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women (r = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/urina , Proteínas de Membrana/urina , Proteínas dos Microfilamentos/urina , Parto/urina , Podócitos/metabolismo , Urina/citologia , Adulto , Aquaporina 2/genética , Aquaporina 2/urina , Pressão Arterial , Cesárea , Creatinina/urina , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Parto/genética , Gravidez , Proteinúria/genética , Proteinúria/urina , RNA Mensageiro/genética , RNA Mensageiro/urina , Fatores de Tempo , Adulto Jovem
10.
J Obstet Gynaecol Res ; 43(5): 873-879, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28188955

RESUMO

AIM: Hyperfiltration is a cause of podocyturia and occurs physiologically in the kidney of pregnant women. Podocyturia is increased in preeclamptic pregnancies, but it is unclear whether there is also any increase in uncomplicated pregnancies. This study was performed to examine whether podocyturia and urine aquaporin 2 mRNA expression are increased in healthy pregnant women (PW) compared to healthy non-pregnant women (NPW). METHODS: Eleven urines obtained from 11 NPW and longitudinal 76 urines from 40 PW with uncomplicated pregnancies (median number [range] of urine samples/person, 2 [1 - 3]) were studied. Determination of protein and creatinine concentrations and number of cells in urine other than blood cells, and quantitative analyses of the mRNA expression of aquaporin 2 (AQP2-mRNA), podocin (Pod-mRNA), and nephrin (Nep-mRNA) were performed using RT-PCR in pelleted urine samples. Podocyturia was monitored with urine Pod- and Nep-mRNA expression levels normalized relative to creatinine. RESULTS: Urine cell density and urine AQP2-, Pod-, and Nep-mRNA expression normalized relative to creatinine were significantly higher in PW than NPW. The number of cells per milligram of creatinine was significantly positively correlated with expression of all three mRNAs with correlation coefficients (R-value) of 0.442, 0.481, and 0.561 for Pod-, Nep-, and AQP2-mRNA, respectively. AQP2-mRNA expression was strongly (R  >  0.8) positively correlated with both Pod- and Nep-mRNA expression. CONCLUSION: Podocyturia monitored by Pod- and Nep-mRNA expression and urine cells expressing AQP2-mRNA were increased in uncomplicated pregnancies compared to healthy non-pregnant women. Urine cells expressing AQP2-mRNA increased with increasing podocyturia in healthy women.


Assuntos
Aquaporina 2/urina , Proteínas de Membrana/urina , Podócitos , Complicações na Gravidez/urina , Transtornos Urinários/urina , Adulto , Feminino , Humanos , Gravidez , RNA Mensageiro/urina
11.
J Obstet Gynaecol Res ; 43(1): 34-41, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27862669

RESUMO

AIM: Podocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. METHODS: Eighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression. This included podocin (Pod-mRNA) and nephrin (Nep-mRNA), using real-time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod- and Nep-mRNA expression levels were corrected by GAPDH. RESULTS: Nephrinuria, proteinuria, Pod-mRNA expression, and Nep-mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R = 0.901, P <  0.001), Pod-mRNA expression level (R = 0.824, P < 0.001), and Nep-mRNA expression level (R  =  0.724, P <  0.001) in urine samples from PE women, while the nephrinuria was significantly correlated with proteinuria alone (R  =  0.419, P <  0.005) in urine samples from normotensive women. CONCLUSION: Nephrinuria reflected well the degrees of proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women.


Assuntos
Proteínas de Membrana/urina , Podócitos/metabolismo , Pré-Eclâmpsia/urina , Proteinúria/urina , Adulto , Creatina/urina , Feminino , Idade Gestacional , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/urina , Gravidez , Fatores de Risco , Adulto Jovem
12.
Sci Rep ; 6: 37442, 2016 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-27874074

RESUMO

This prospective observational study compare urine nephrin:creatinine ratio (NCR, ng/mg) with serum soluble fms-like tyrosine kinase-1:placental growth factor ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired urine/blood samples collected simultaneously from 254 women at median gestational week (GW) 24 (range, 22-27) without hypertension or significant proteinuria in pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0-38.6) and 35.3 (27.6-38.6), respectively, and were diagnosed with PE at GW 35.7 (27.6-38.6). The 90th percentile level determined in 239 women normotensive throughout pregnancy gave NCR (139) sensitivity and positive predictive values (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40% (6/15) and 20% (6/30), respectively. Relative risks (95%CI) of later PE were 10.0 (3.82-26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91-13.0; 20% [6/30] vs. 4.0% [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17% (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus, 2nd trimester NCR was superior to FPR for PE prediction.


Assuntos
Creatinina/urina , Proteínas de Membrana/urina , Fator de Crescimento Placentário/urina , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/urina , Segundo Trimestre da Gravidez/urina , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/urina , Adulto , Demografia , Feminino , Humanos , Hipertensão/urina , Programas de Rastreamento , Pessoa de Meia-Idade , Gravidez , Proteinúria/urina , Solubilidade , Adulto Jovem
13.
BMJ Open ; 6(8): e011229, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27486123

RESUMO

OBJECTIVES: To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE). DESIGN: Prospective observational study. SETTING: A single university hospital. Changes in urinary nephrin:creatinine ratio (NCR, ng/mg) and protein:creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR>0.27. PE was diagnosed in women with both SPIP and hypertension. PARTICIPANTS: 89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively. RESULTS: PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In contrast, NCR did not change significantly despite significant increases in PCR in 75 women with normotensive pregnancies defined as neither SPIP nor hypertension, indicating that there was little increase in nephrinuria over the physiological range of proteinuria in pregnancy. Relative risk of later development of PE among asymptomatic second and third trimester women with NCR (ng/mg) >122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR≤122 at that time. CONCLUSIONS: Nephrinuria was unlikely to increase in normal pregnancy. A certain NCR cut-off may efficiently differentiate women at higher risk of PE.


Assuntos
Proteínas de Membrana/urina , Pré-Eclâmpsia/diagnóstico , Adulto , Biomarcadores/urina , Creatinina/urina , Estudos de Viabilidade , Feminino , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Paridade , Gravidez , Trimestres da Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Prospectivos , Proteinúria/diagnóstico , Medição de Risco , Adulto Jovem
14.
Sci Rep ; 6: 24258, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27052160

RESUMO

Podocyte injury has been suggested to induce phenotypic alteration of glomerular podocytes and accelerate the detachment of podocytes from the glomeruli resulting in podocyturia. However, it is not clear whether podocyte phenotypic alteration occurs in the urine of women with preeclampsia (PE). Seventy-seven and 116 pelleted urine samples from 38 and 18 women at various stages of normal and PE pregnancies, respectively underwent quantitative analysis of podocyte-specific or associated protein mRNA expression, including podocin, nephrin, and synaptopodin using RT-PCR. Significant proteinuria in pregnancy (SPIP) is defined as protein:creatinine ratio (P/Cr, mg/mg) ≥ 0.27 in the urine supernatant. All three urine-pellet mRNAs expression levels were significantly positively correlated with P/Cr levels, suggesting that podocyturia increased with proteinuria. The podocin:nephrin mRNA ratio (PNR) and synaptopodin:nephrin mRNA ratio (SNR) increased significantly with increasing P/Cr, while the podocin:synaptopodin mRNA ratio (PSR) did not change significantly according to P/Cr, resulting in significantly higher PNR and SNR, but not PSR levels, in urine from PE women with than without SPIP. The PNR, SNR, and PSR in urine from PE women before onset of SPIP were comparable to those from controls. Thus, nephrin mRNA expression was reduced in the podocytes recovered from PE women.


Assuntos
Expressão Gênica , Podócitos/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/urina , Adulto , Adesão Celular/genética , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/urina , Proteínas de Membrana/genética , Proteínas de Membrana/urina , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/urina , Gravidez , Proteinúria/genética , Proteinúria/urina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Adulto Jovem
15.
Thromb Res ; 138: 43-48, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26826507

RESUMO

BACKGROUND: Gestational thrombocytopenia is more likely to occur in twin than singleton pregnancies. However, it is unclear whether platelets are more reactive in twin than singleton pregnancies. METHODS: Changes in spontaneous platelet aggregation and concomitant fall in platelet count were examined over 90min after blood sampling in 171 and 52 citrated whole blood (CWB) samples from 59 and 17 women with singleton and twin pregnancies, respectively. Soluble P-selectin (sP-selectin) levels in the plasma were also determined. RESULTS: CWB 60min after blood sampling during 2nd trimester exhibited significantly larger numbers of platelet aggregates (1297±1600 vs. 497±432/µl, P=0.040) concomitant with significantly greater net decrease in platelet count (152±55 vs. 115±45×10(9)/µl, P=0.036) in twin than singleton pregnancies, respectively. This was followed by significantly lower 3rd trimester platelet count (181±43 vs. 229±62×10(9)/l, P=0.009) with significantly greater mean platelet volume (8.0±1.2 vs. 7.1±1.1fl, P=0.021) in twin than singleton pregnancies, respectively. The 3rd trimester sP-selectin per platelet was significantly higher in twin than singleton pregnancies. CONCLUSIONS: Platelets were more reactive in the 2nd trimester of twin than singleton pregnancies. This enhanced platelet reactivity may explain the decreased platelet count in the 3rd trimester of twin pregnancy.


Assuntos
Plaquetas/citologia , Agregação Plaquetária , Gravidez de Gêmeos/sangue , Adulto , Feminino , Humanos , Selectina-P/sangue , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez/sangue , Terceiro Trimestre da Gravidez , Trombocitopenia/sangue , Trombocitopenia/complicações
16.
Reprod Biol ; 15(3): 131-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26370455

RESUMO

Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57(Kip2), devoid of the imprinted paternal allele (p57(Kip2+/-)), are known to develop hypertension during pregnancy. To determine whether fetal Atg9a is involved in the intrauterine survival and growth of fetal mice, this study was performed on Atg9a heterozygous (Atg9a(+/-)) pregnant mice with and without p57(Kip2+/-). The pregnant mice heterozygous for both knockout alleles of Atg9a and p57(Kip2) (Atg9a(+/-)/p57(Kip2+/-)), but not those heterozygous for Atg9a alone, developed hypertension during pregnancy. Placental expression of Atg9a mRNA was significantly decreased in the Atg9a(-/-) mice compared to Atg9a(+/-) or Atg9a(+/+) mice. The Atg9a(-/-) fetal mice exhibited significantly retarded growth and were more likely to die in utero compared to Atg9a(+/+) and Atg9a(+/-) fetal mice. Growth retardation was observed in the presence of maternal hypertension in Atg9a(-/-) fetal mice. These results suggest that Atg9a(-/-) fetal mice from pregnant dams heterozygous for both knockout alleles of Atg9a and p57(Kip2) are more susceptible to hypertensive stress than fetuses with intact autophagic machinery.


Assuntos
Autofagia/genética , Desenvolvimento Fetal/genética , Retardo do Crescimento Fetal/genética , Hipertensão Induzida pela Gravidez/genética , Proteínas de Membrana/genética , Proteínas de Transporte Vesicular/genética , Alelos , Animais , Proteínas Relacionadas à Autofagia , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Feminino , Retardo do Crescimento Fetal/metabolismo , Heterozigoto , Hipertensão Induzida pela Gravidez/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Gravidez , Proteínas de Transporte Vesicular/metabolismo
17.
Clin Chim Acta ; 448: 60-4, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26102281

RESUMO

BACKGROUND: It was recently suggested that platelet reactivity is reduced in early pregnancy. This study was performed to determine whether the citrated whole blood from 33 pregnant women in their first trimester showed spontaneous platelet aggregation and whether it differed in extent from that of 11 non-pregnant women. METHODS: The platelet count and number of platelet aggregates (PA) were serially determined in the same citrated whole blood specimens at 15, 30, 45, 60, 75, and 90min after blood sampling using a hematology analyzer. RESULTS: The number of PA increased significantly at 30min and thereafter in both groups, but was consistently lower for pregnant than non-pregnant women over the 90-min observation period. The platelet count decreased significantly in a time-dependent manner in both groups, but was significantly lower at 30 and 90min for non-pregnant than pregnant women. The number of PA showed a significant positive correlation with net decrease in platelet count for both pregnant and non-pregnant women. PA counts were also significantly positively correlated with the mean platelet volume. CONCLUSION: Platelet reactivity monitored by the increase in number of PA and the fall in platelet count was reduced in early pregnancy compared with non-pregnant healthy controls.


Assuntos
Ácido Cítrico/química , Agregação Plaquetária , Primeiro Trimestre da Gravidez/sangue , Adulto , Feminino , Humanos , Gravidez
18.
ESC Heart Fail ; 2(3): 208-215, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28834676

RESUMO

AIMS: Echocardiography is necessary for the diagnosis of peripartum cardiomyopathy (PPCM). Multifetal pregnancies (MFP) and hypertensive disorders (HD) are prominent risk factors for PPCM. To determine which blood variables exhibit greater change in a late stage of pregnancy in women with MFP and/or HD compared with women with normotensive singleton pregnancies. METHODS AND RESULTS: Serum levels of six variables-high-sensitive troponin I (hs-TnI), N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP), myoglobin, creatine kinase-myocardial band, ferritin, and prolactin-were compared between 29 women with MFP (n = 13) and/or HD (n = 18) and 100 women with normotensive singleton pregnancies (control group). None of 129 women developed PPCM. All variables increased significantly peripartum in both groups. In 29 women with MFP and/or HD, the elevated hs-TnI and NT-proBNP levels (median) were significantly higher compared with the control group (5.4 vs. 3.7 pg/mL for hs-TnI with P = 0.002, 185 vs. 68 pg/mL for NT-proBNP with P = 0.007), and the prevalence rate of more than 90th percentile value specific for the 129 women was significantly more frequent for hs-TnI (>12.2 pg/mL; 31% [9/29] vs. 4.0% [4/100], P < 0.001) and tended to be more frequent for NT-proBNP (>342 pg/mL; 21% [6/29] vs. 7.0%, P = 0.072). CONCLUSIONS: Both hs-TnI and NT-proBNP were likely to increase markedly in women with MFP and/or HD. The combination of hs-TnI and NT-proBNP may contribute to better selection of candidates for echocardiography.

19.
Pediatr Res ; 76(5): 453-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25105258

RESUMO

BACKGROUND: Genetic variations associated with interstitial lung diseases (ILD) have not been extensively studied in Japanese infants. METHODS: Forty-three infants with unexplained lung dysfunction were studied. All 43, 22, and 17 infants underwent analyses of surfactant protein (SP)-C gene (SFTPC) and ATP-binding cassette A3 gene (ABCA3), SP-B gene (SFTPB), and SP-B western blotting, respectively. Two and four underwent assessment of granulocyte macrophage colony-stimulating factor-stimulating phosphorylation of signal transducer and activator of transcription-5 (pSTAT-5) and analyses of FOXF1 gene (FOXF1), respectively. RESULTS: ILD were diagnosed clinically in nine infants: four, three, and two had interstitial pneumonitis, hereditary pulmonary alveolar proteinosis (hPAP), and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), respectively. Genetic variations considered responsible were detected in six (67%) of the nine infants with ILD: three with hPAP (SFTPC p.Leu45Arg and p.Gln145fs, and ABCA3 p.Arg1583Trp/p.Val1495CysfsX21), two with interstitial pneumonitis (SFTPC p.Lys63Glu and p.Ser72Asn/p.Gly100Ala), and one with ACD/MPV (FOXF1 p.Leu300ArgfsX79). None showed SFTPB mutations or defects in pSTAT-5. The 17 bronchoalveolar lavage or tracheal aspirates contained enough SP-B protein. CONCLUSION: The SP-C abnormality was most prevalent, and SP-B deficiency was rare in Japanese infants with hereditary ILD.


Assuntos
Variação Genética , Doenças Pulmonares Intersticiais/genética , Transportadores de Cassetes de Ligação de ATP/genética , Idade de Início , Povo Asiático/genética , Feminino , Fatores de Transcrição Forkhead/genética , Marcadores Genéticos , Predisposição Genética para Doença , Hereditariedade , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Leucócitos Mononucleares/química , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etnologia , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Fenótipo , Fosforilação , Proteinose Alveolar Pulmonar/congênito , Proteinose Alveolar Pulmonar/etnologia , Proteinose Alveolar Pulmonar/genética , Proteína B Associada a Surfactante Pulmonar/análise , Proteína B Associada a Surfactante Pulmonar/deficiência , Proteína B Associada a Surfactante Pulmonar/genética , Proteína C Associada a Surfactante Pulmonar/genética , Sistema de Registros , Fator de Transcrição STAT5/análise
20.
J Obstet Gynaecol Res ; 40(5): 1441-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24750396

RESUMO

Entamoeba histolytica is estimated to infect approximately 1% of the global population. In Japan, the prevalence of amebic dysentery has been increasing, with more than 800 patients newly diagnosed annually. However, genital infection with E. histolytica is uncommon even in endemic areas. We present a case of vaginitis caused by E. histolytica. A 50-year-old Japanese woman without history of overseas travel presented to a nearby clinic with increased vaginal discharge. She had hemorrhagic erosion at the uterine cervix with yellowish vaginal discharge, and was referred to our hospital for exclusion of malignancy. Cervical cytology revealed periodic acid-Schiff-positive protozoa not aggregating around squamous cells, and thus amebic vaginitis was suspected. We performed polymerase chain reaction (PCR) analyses and identified E. histolytica. The vaginitis was treated with metronidazole, and the disappearance of amebic protozoa was confirmed by cytology and PCR. Therefore, it may be important to obtain early diagnosis by cervical cytology and PCR.


Assuntos
Entamoeba histolytica/genética , Entamebíase/diagnóstico , Reação em Cadeia da Polimerase/métodos , Doenças do Colo do Útero/diagnóstico , Sequência de Bases , Feminino , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular
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