Browsing by Author "Gómez Mora, Ricardo Alberto"
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- ItemA Novel ERAP2 Haplotype Structure in a Chilean Population: Implications for ERAP2 Protein Expression and Preeclampsia Risk(2013) Vanhille, Derek L.; Hill, Lori D.; Hilliard, DaShaunda D.; Lee, Eun D.; Teves, Maria E.; Srinivas, Sindhu; Kusanovic, Juan Pedro; Gómez Mora, Ricardo Alberto; Stratikos, Efstratios
- ItemA rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery(2006) Nien, J. K.; Yoon, B. H.; Espinoza, J.; Kusanovic, Juan Pedro; Erez, O.; Soto, E.; Richani, K.; Gómez Mora, Ricardo Alberto; Hassan, S.; Mazor, M.; Edwin, S.; Bahado-Singh, R.; Romero, R.Objective: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated not only in patients with intra-amniotic infection, but also in patients with negative amniotic fluid cultures who deliver preterm neonates. The objective of this study was to determine whether the results of a rapid MMP-8 bedside test predict imminent preterm delivery. This test can be performed in 15 minutes and without laboratory equipment. Study design: Amniotic fluid was retrieved from 331 patients admitted with increased preterm uterine contractions and intact membranes who met the inclusion criteria. Amniotic fluid was processed for microbial cultures, Gram stain, glucose concentration, and white blood cell count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed after delivery. End points included spontaneous preterm delivery within 48 hours, 7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios were calculated. Results: The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5% (80/327), respectively (4 patients with augmentation of labor were excluded). A positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the identification of patients who delivered spontaneously within 48 hours, and 94% (31/33) for patients who were delivered within 7 days and 14 days (likelihood ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196], respectively). Conclusion: The MMP-8 rapid test can identify patients at risk for preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test result can identify patients with intraamniotic infection/inflammation with a high sensitivity and specificity. This rapid test will give clinicians a fast and accurate assessment of the inflammatory status of the amniotic cavity and allow for better identification of patients at risk for impending preterm delivery.
- ItemAdiponectin in severe preeclampsia(2007) Nien, J. K.; Mazaki-Tovi, S.; Romero, R.; Erez, O.; Kusanovic, Juan Pedro; Gotsch, F.; Pineles, B. L.; Gómez Mora, Ricardo Alberto; Edwin, S.; Mazor, M.; Espinoza, J.; Yoon, B. H.; Hassan, S. S.Aims: Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods: This case-control study included two groups: (1) patients with severe preeclampsia (ns50) and (2) patients with normal pregnancies (ns150). Pulsedwave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results: (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions: Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolicallyaltered, anti-angiogenic and pro-atherogenic state of severe preeclampsia.
- ItemAmniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition(2008) Chaiworapongsa, T.; Erez, O.; Kusanovic, Juan Pedro; Vaisbuch, E.; Mazaki-Tovi, S.; Gotsch, F.; Than, N. G.; Mittal, P.; Kim, Y. M.; Camacho, N.; Edwin, S.; Gómez Mora, Ricardo Alberto; Hassan, S. S.; Romero, R.Objective: Heat shock protein (HSP) 70, a conserved member of the stress protein family, is produced in almost all cell types in response to a wide range of stressful stimuli, and its production has a survival value. Evidence suggests that extracellular HSP70 is involved in the activation of the innate and adaptive immune response. Furthermore, increased mRNA expression of HSP70 has been observed in human fetal membranes following endotoxin stimulation. This study was conducted to determine the changes in amniotic fluid HSP70 concentrations during pregnancy, term and preterm parturition, intra-amniotic infection (IAI), and histologic chorioamnionitis. Study design. A cross-sectional study was conducted in 376 pregnant women in the following groups: (1) women with a normal pregnancy who were classified into the following categories: (a) women in the mid-trimester (14–18 weeks) who underwent amniocentesis for genetic indications and delivered normal infants at term (n¼72); (b) women at term not in labor (n ¼ 23); and (c) those at term in labor (n ¼ 48). (2) Women with spontaneous preterm labor and intact membranes who were subdivided into the following categories: (a) preterm labor who delivered at term without IAI (n ¼ 42); (b) preterm labor who delivered preterm without IAI (n ¼ 57); and (c) preterm labor and delivery with IAI (n ¼ 30). (3) Women with preterm prelabor rupture of membranes (PROM) with (n ¼ 50) and without (n ¼ 54) IAI. Among patients with preterm labor with intact membranes and preterm PROM who delivered within 72 hours of amniocentesis, placenta, umbilical cord, and chorioamniotic membranes were collected and assessed for the presence or absence of acute inflammatory lesions in the extraplacental membranes (histologic chorioamnionitis) and/or umbilical cords (funisitis). HSP70 concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of 50.05 was considered statistically significant. Results. Immunoreactive HSP70 was detected in 88% (332/376) of amniotic fluid samples. The median amniotic fluid HSP70 concentration was significantly higher in women at term without labor than in those in the mid-trimester (term no labor: median 34.9 ng/mL, range 0–78.1 ng/mL vs. mid-trimester; median 6.6 ng/mL, range 0–20.8 ng/mL; p50.001). Among patients with spontaneous preterm labor and preterm PROM, those with IAI had a significantly higher median amniotic fluid HSP70 concentration than those without IAI (preterm labor with IAI: median 82.9 ng/mL, range 0–500 ng/mL vs. preterm labor without IAI: median 41.7 ng/mL, range 0–244 ng/mL; p ¼ 0.001; preterm PROM with IAI: median 86.5 ng/mL, range 0– 428 ng/mL vs. preterm PROM without IAI: median 55.9 ng/mL, range 14.9–299.9 ng/mL; p ¼ 0.007). There was no significant difference in the median amniotic fluid HSP70 concentration between patients with preterm labor who delivered preterm without IAI and those who delivered at term (p ¼ 0.6). However, among patients with preterm labor without IAI, there was an inverse relationship between amniotic fluid concentration of HSP70 and the amniocentesis-to-spontaneous delivery interval (Spearman’s Rho ¼70.26; p ¼ 0.02). Patients with histologic chorioamnionitis/funisitis had a significantly higher median amniotic fluid HSP70 concentration than those without inflammation (inflammation: median 108.7 ng/mL, range 0– 500 ng/mL vs. without inflammation: median 67.9 ng/mL, range 7.1–299.9 ng/mL; p ¼ 0.02). Women at term in labor had a median amniotic fluid concentration of HSP70 significantly higher than those not in labor (term in labor: median 60.7 ng/mL, range 0–359.9 ng/mL vs. term not in labor: median 34.9 ng/mL, range 0–78.1 ng/mL; p ¼ 0.02).
- ItemDoes a perturbation in visfatin homeostasis participate in the phenotype definition of preeclampsia and SGA?(2009) Kim, Sun Kwon; Romero, Roberto; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Than, Nandor; Gotsch, Francesca; Nhan-Chang, Chia-Ling; Chiaworapongsa, Tinnakorn; Gómez Mora, Ricardo Alberto; Mittal, Pooja; Hassan, Sonia; Pacora, Percy; Yeo, LamiObjective: Women with preeclampsia (PE) and those who delivered a small for gestational age (SGA) neonate share several mechanisms of disease including: chronic uteroplacental ischemia and failure of physiologic transformation of the spiral arteries. However, the clinical manifestation of these obstetrical syndromes is remarkably different. It has been proposed that an altered maternal metabolic state, as well as a unique circulating cytokines milieu, predispose women to develop either PE or SGA (Ness&Sibai AJOG 2006;195:40). Compelling evidence suggests that adipose tissue orchestrates both metabolic pathways and immunological responses via the production of adipokines. Visfatin is a novel adipocytokine with metabolic and immunomodulating properties. The objective of this study was to determine whether PE and SGA are associated with alterations in maternal circulating visfatin concentrations. Methods: This cross-sectional study included 255 pregnant women in the following groups: 1) normal pregnancy (n = 158); 2) patients with PE (n = 43) of which 32 had an AGA and 11 had an SGA neonate; and 3) patients who delivered an SGA neonate without PE (n = 54). Maternal plasma visfatin concentrations were measured by ELISA. Non-parametric tests and multiple linear regression analysis were used. Results: 1) Women who delivered an SGA neonate had higher median maternal plasma visfatin concentration than those with normal pregnancy (median: 20.0ng/ml, interquartile range: 17.2–24.6 vs. 15.2 ng/ml, 12.1–19.2, respectively; p. Conclusion: 1) Mothers with SGA, but not with PE, had a higher maternal plasma visfatin concentration than those with a normal pregnancy; 2) This finding suggests differential involvement of adipokines in SGA and PE; 3) We propose that perturbation of adipokine homeostasis may be implicated in the phenotypic definition and distinction of PE and SGA
- ItemEarly Rapid Growth, Early Birth: Accelerated Fetal Growth and Spontaneous Late Preterm Birth(2009) Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis; Hassa, Sonia; Gómez Mora, Ricardo Alberto; Nien Shy, Jyh-Kae; Edward A. Frongillo; Romero, Roberto
- ItemEpistasis between COMT and MTHFR in Maternal-Fetal Dyads Is Associated with Increased Risk for Preeclampsia(2011) Hill, Lori D.; York, Timothy P.; Kusanovic Pivcevic, Juan Pedro; Gómez Mora, Ricardo Alberto; Eaves, Lindon J.; Romero, Roberto; Strauss, Jerome F.Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C→T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor “T” allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR.
- ItemEvidence for a polarized Th1 response in the maternal circulation in women with preterm labor and intra-amniotic inflammation/infection(2006) Espinoza, Jimmy; Kusanovic, Juan Pedro; Hassan, Sonia; Edwin, Samuel S.; Gotsch, Francesca; Kim, Chong Jai; Than, Nandor Gabor; Erez, Offer; Nien, Jyh Kae; Gómez Mora, Ricardo Alberto; Yoon, Bo Hyun; Romer, RobertoOBJECTIVE: Most work examining the immune response to intra-amniotic infection has focused on the study of amniotic fluid (AF) cytokines. An adequate characterization of the full range of maternal pro- and antiinflammatory cytokines is lacking. This is important, because of emerging evidence that complications of infection result from an anti-inflammatory response. The purpose of this study was to characterize the maternal cytokine response in women with preterm labor with and without intra-amniotic infection/inflammation (IAI). STUDY DESIGN: This study focused on patients with preterm labor in the following groups: 1) term delivery (n = 157); 2) preterm delivery without IAI (n = 126); and 3) IAI (n = 50). IAI was defined as a positive AF culture or an elevated AF WBC count. Maternal plasma concentrations of interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, interferon gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha were determined. A p!0.05 was considered significant. RESULTS: 1) Patients with IAI had higher plasma concentrations of IL-6 than those without IAI who delivered preterm [median: 12.5 pg/ml, range: 0-355.5 vs.7.4 pg/ml, range: 0.74-179.3; p = 0.04), and those who delivered at term (median: 5 pg/ml, range: 0-541.4; p = 0.01); 2) Patients with IAI had higher plasma concentrations of IL-8 than those who delivered at term (median:11.1 pg/ml, range: 0.29-82 vs. median: 6 pg/ml, range: 0.4-84.3; p = 0.02) but not than those without IAI who delivered preterm (median: 7.9, range: 1.3-90.2; pO0.05); and 3) There were no significant differences in the plasma concentrations of the rest of the cytokines (11 of 13) among groups. CONCLUSION: IL6 and IL8 are increased in the maternal circulation in cases of intra-amniotic infection/inflammation. The lack of a demonstrable anti-inflammatory response is in sharp contrast to what has been reported in non-pregnant patients
- Item¿Existe un aumento de los nacimientos en Chile en el período 2000-2009? Análisis de los principales indicadores materno-infantiles de la década(2011) González Pérez, Rogelio Iván; Nien Shy, Jyh-Kae; Vera Pérez-Gacitúa, Claudio Mauricio; Poblete L., José A.; Carvajal C., Jorge A.; González O., Miriam; Guzmán B., Eghon; Gómez Mora, Ricardo Alberto; Abarca E., Montserrat; Oyarzún Ebensperger, EnriqueObjetivo. Describir la tendencia en los nacimientos y los principales indicadores materno-infantiles en Chile desde el año 2000 al 2009. Método. Se realiza un análisis descriptivo de la información obtenida desde el Ministerio de Salud de Chile para el período estudiado. Resultados. Durante el período estudiado nacen aproximadamente 2.400.000 personas, se observa un significativo aumento en su número a partir del año 2004 al 2009 (+9,7%). Las tasas de mortalidad neonatal precoz, tardía, post neonatal e infantil fueron de 3,86; 1,18; 2,54 y 7,58 por 1000 nacidos vivos durante el año 2009, presentado un porcentaje de disminución de un 13,5; 8,4; 16,2; 13,7% respectivamente en comparación al año 2000. La mortalidad materna disminuyó en un 13,2% desde 19,7 a 17,1 por cien mil nacimientos en el mismo período. La prematurez (<37s) incrementa significativamente en un 20,82% (de 5,96 a 7,2%). El mayor cambio se observa entre las 32-33 y 34-36 semanas (aumento de un 18% y 32%, respectivamente). El porcentaje de nacimientos múltiples (dos) aumentó significativamente en un 11%, desde 1,66 a 1,84 por cien nacimientos. Conclusión. Durante el período estudiado se observa un aumento significativo de los nacimientos totales, del porcentaje de primigestas y de madres sobre 40 años. Se presenta un aumento de la prematurez, del bajo peso al nacer y del porcentaje de embarazos múltiples. Los cambios observados se asocian aun a una mejoría de los indicadores neonatales.
- ItemLipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B-4(2016) Maddipati, K.; Romero, R.; Chaiworapongsa, T.; Chaemsaithong, P.; Zhou, S.; Xu, Z.; Tarca, A.; Kusanovic, Juan Pedro; Gómez Mora, Ricardo Alberto; Chaiyasit, N.; Honn, K.
- ItemLow circulating maternal adiponectin in patients with pyelonephritis: adiponectin at the crossroads of pregnancy and infection(2010) Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Kwon Kim, Sun; Gotsch, Francesca; Lamont, Ronald; Ogge, Giovanna; Pacora, Percy; Goncalves, Luis; Jai Kim, Chong; Gómez Mora, Ricardo Alberto; Espinoza, Jimmy; Hassan, Sonia S.; Kusanovic, Juan PedroObjective: An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested. Thus, the aim of this study was to determine if pyelonephritis during pregnancy is associated with changes in maternal serum adiponectin concentrations. Study design: This cross-sectional study included women in the following groups: 1) normal pregnant women (ns200); and 2) pregnant women with pyelonephritis (ns50). Maternal plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) The median maternal plasma adiponectin concentration was lower in patients with pyelonephritis than in those with a normal pregnancy (P-0.001); 2) among pregnant women with a normal weight, patients with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (P-0.001); 3) similarly, among overweight/obese patients, those with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (P-0.001); and 4) the presence of pyelonephritis was independently associated with maternal plasma adiponectin concentrations after adjustment for maternal age, smoking, gestational age at sampling, and pregestational body mass index (BMI). Conclusion: 1) The findings that acute pyelonephritis in pregnancy is characterized by low maternal plasma concentrations of adiponectin in both lean and overweight/obese patients are novel and concur with the antiinflammatory properties of adiponectin; and 2) the results of this study support the notion that adiponectin may play a role in the intricate interface between inflammation and metabolism during pregnancy
- ItemMetabolomics in premature labor: A novel approach to identify patients at risk for preterm delivery(2010) Romero, Roberto; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Gómez Mora, Ricardo Alberto; Nien Shy, Jyh-Kae; Yoon, Bo Hyun; Mazor, Moshe; Luo, Jingqin; Banks, David; Ryals, John; Beecher, ChrisObjective. Biomarkers for preterm labor (PTL) and delivery can be discovered through the analysis of the transcriptome (transcriptomics) and protein composition (proteomics). Characterization of the global changes in low-molecular weight compounds which constitute the ‘metabolic network’ of cells (metabolome) is now possible by using a ‘metabolomics’ approach. Metabolomic profiling has special advantages over transcriptomics and proteomics since the metabolic network is downstream from gene expression and protein synthesis, and thus more closely reflects cell activity at a functional level. This study was conducted to determine if metabolomic profiling of the amniotic fluid can identify women with spontaneous PTL at risk for preterm delivery, regardless of the presence or absence of intraamniotic infection/inflammation (IAI). Study Design. Two retrospective cross-sectional studies were conducted, including three groups of pregnant women with spontaneous PTL and intact membranes: (1) PTL who delivered at term; (2) PTL without IAI who delivered preterm; and (3) PTL with IAI who delivered preterm. The first was an exploratory study that included 16, 19, and 20 patients in groups 1, 2, and 3, respectively. The second study included 40, 33, and 40 patients in groups 1, 2, and 3, respectively. Amniotic fluid metabolic profiling was performed by combining chemical separation (with gas and liquid chromatography) and mass spectrometry. Compounds were identified using authentic standards. The data were analyzed using discriminant analysis for the first study and Random Forest for the second. Results. (1) In the first study, metabolomic profiling of the amniotic fluid was able to identify patients as belonging to the correct clinical group with an overall 96.3% (53/55) accuracy; 15 of 16 patients with PTL who delivered at term were correctly classified; all patients with PTL without IAI who delivered preterm neonates were correctly identified as such (19/19), while 19/20 patients with PTL and IAI were correctly classified. (2) In the second study, metabolomic profiling was able to identify patients as belonging to the correct clinical group with an accuracy of 88.5% (100/113); 39 of 40 patients with PTL who delivered at term were correctly classified; 29 of 33 patients with PTL without IAI who delivered preterm neonates were correctly classified. Among patients with PTL and IAI, 32/40 were correctly classified. The metabolites responsible for the classification of patients in different clinical groups were identified. A preliminary draft of the human amniotic fluid metabolome was generated and found to contain products of the intermediate metabolism of mammalian cells and xenobiotic compounds (e.g. bacterial products and Salicylamide). Conclusion. Among patients with spontaneous PTL with intact membranes, metabolic profiling of the amniotic fluid can be used to assess the risk of preterm delivery in the presence or absence of infection/inflammation.