Browsing by Author "Krause, Bernardo J."

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    Chronic Intermittent Hypoxia-Induced Vascular Dysfunction in Rats is Reverted by N-Acetylcysteine Supplementation and Arginase Inhibition
    (2018) Krause, Bernardo J.; Casanello Toledo, Paola Cecilia; Dias, Ana C.; Arias, Paulina; Velarde, Victoria; Arenas Menéndez, German Alberto; Preite, Marcelo Daniel; Iturriaga Agüera, Rodrigo
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    INTRAUTERINE GROWTH RESTRICTION IN GUINEA PIG IMPAIRS UMBILICAL AND SYSTEMIC VASCULAR FUNCTION
    (W B SAUNDERS CO LTD, 2015) Herrera, Emilio A.; Schneider, Daniela; Alegria, Rene; Figueroa, Esteban; Villanueva, Cristian; Farias, Marcelo; Casanello, Paola; Krause, Bernardo J.
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    Nonsyndromic orofacial clefts in Chile: LINE-1 methylation and MTHFR variants
    (2020) Cáceres Rojas, Gabriela; Salamanca, Carlos; Krause, Bernardo J.; Recabarren, Andrea S.; Pantoja, Roberto; Leiva, Noemi; Pardo, Rosa; Santos Martín, José Luis; Suazo, José
    Aim: To evaluate the risk of nonsyndromic orofacial clefts (NSOFCs) associated with LINE-1 methylation, as a marker of global DNA methylation, and the effect of MTHFR functional variants on this variable. Patients & methods: LINE-1 methylation was evaluated by bisulfite modification coupled to DNA pyrosequencing in 95 NSOFC cases and 95 controls. In these subjects, MTHFR genotypes for variants c.C677T (rs1801133) and c.A1298C (rs1801131) were obtained. Results: Middle levels (second tertile) of LINE-1 methylation increase the risk of NSOFCs. In addition, LINE-1 methylation depends on c.A1298C genotypes in controls but not in cases. Conclusion: A nonlinear association between global DNA methylation and NSOFCs was detected in this Chilean population, which appears to be influenced by MTHFR functional variants.
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    Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep
    (INT PEDIATRIC RESEARCH FOUNDATION, INC, 2008) Herrera, Emilio A.; Ebensperger, German; Krause, Bernardo J.; Riquelme, Raquel A.; Reyes, Roberto V.; Capetillo, Maria; Gonzalez, Sergio; Parer, Julian T.; Llanos, Anibal J.
    Perinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small Pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates.
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    The asthma predictive index as a surrogate diagnostic tool in preschoolers: Analysis of a longitudinal birth cohort
    (WILEY, 2021) Castro Rodriguez, Jose A.; Forno, Erick; Padilla, Oslando; Casanello, Paola; Krause, Bernardo J.; Borzutzky Schachter, Arturo
    Diagnosing asthma in preschool children remains an unsolved challenge, at a time when early identification would allow for better education and treatment to prevent morbidity and lung function deterioration. Objective To evaluate if the asthma predictive index (API) can be used as surrogate for asthma diagnosis in preschoolers. Methods Birth cohort of 339 pregnant women enrolled at delivery and their offspring, who were followed for atopy, wheezing, and other respiratory illnesses through 30 months of age. The API was determined at 30 months of age by the researchers; and examined its association with physician-diagnosed asthma during the first 30 months, made independently by the primary care physician not involved in the study. Results Among 307 offspring with complete follow-up, 44 (14.3%) were API+. Maternal body mass index, maternal education, past oral contraceptive use, birthweight, placenta weight, age of daycare at 12 m, gastroesophageal reflux disease at 12 m, acute otitis media at 18 m, bronchiolitis, croup and pneumonia, cord blood adiponectin were all associated with API+. In the multivariable analysis, API+ was associated with almost sixfold odds of asthma diagnosis (adjusted OR = 5.7, 95% CI [2.6-12.3]), after adjusting for the relevant covariates above including respiratory infections like bronchiolitis and pneumonia. The API sensitivity was 48%, specificity 92%, 61% PPV, 88% NPV, 6.4 LR+, 0.56 LR-, 0.84 diagnosis accuracy. The adjusted odds for asthma was 11.4. Conclusions This longitudinal birth cohort suggests, for first time, that API (a structured definition for asthma), could be used as a diagnostic tool, not only as a prognostic tool, in toddlers and preschoolers.