Serum uric acid levels and risk of developing preeclampsia

Si bien se conoce que existe una asociación entre los niveles elevados de ácido úrico y la preeclampsia, el debate sobre su aplicación clínica aún está abierto. Nuestro objetivo fue estudiar la utilidad del dosaje periódico del ácido úrico sérico durante el embarazo para identificar gestantes con mayor riesgo de desarrollar preeclampsia. Realizamos un estudio retrospectivo en gestantes primíparas: 79 normotensas y 79 con preeclampsia atendidas en el Hospital Nacional Posadas durante el año 2010. Se analizaron los niveles séricos de ácido úrico, creatinina y urea, y los datos de proteinuria de las historias clínicas de las mujeres embarazadas. Los niveles de ácido úrico fueron similares en ambos grupos durante la primera mitad de la gestación. Sin embargo, a partir de la semana 20, el ácido úrico se incrementó 1.5 veces en gestantes preeclámpticas, sin cambios en la uremia y creatininemia, descartándose así el compromiso renal. Además, encontramos que niveles más altos de ácido úrico se correlacionaban con bajo peso del recién nacido. También vimos que las gestantes con antecedentes familiares de hipertensión eran más propensas a desarrollar esta condición. Por otro lado, no observamos una relación directa ni con el sexo fetal ni con el tiempo de aparición de los síntomas clínicos. Estos hallazgos sugieren que los cambios en las concentraciones de ácido úrico se deberían a alteraciones en los estadios iniciales de la preeclampsia. Por ello, la monitorización de los niveles del mismo durante el embarazo podría contribuir al abordaje precoz de este desorden gestacional.It is well known that preeclampsia is associated to high uric acid levels, but the clinical assessment of this relationship is still under consideration. Our research was to evaluate if periodic doses of uric acid during pregnancy might help to identify a high risk group prior to the onset of preeclampsia. We conducted a retrospective investigation in 79 primary gestates with normal blood pressure and 79 women with preeclampsia who were assisted at Hospital Nacional Posadas during 2010. Serum uric acid levels, creatininemia, uremia, and proteinuria data from the clinical records of the pregnant women were considered. Uric acid levels were similar in both groups during the first half of gestation. However, as of the 20th week, uric acid increased 1.5-times in preeclamptic women with no changes in creatinine and urea, confirming that these patients had no renal complications. Furthermore, we noted that higher levels of uric acid correlated with low birth weight. We also observed that pregnant women with a family history of hypertension were more likely to develop this condition. Moreover, we did not find a direct relationship with the fetal sex or the appearance of clinical symptoms. The analytical evidence suggests that changes in uric acid concentrations may be due to metabolic alterations at the initial stages of preeclampsia. Therefore, we propose that monitoring levels of uric acid during pregnancy might contribute to the early control of this condition.Fil: Corominas, Ana. Hospital Nacional Prof. Dr. Alejandro Posadas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas; ArgentinaFil: Balconi, Silvia. Hospital Nacional Prof. Dr. Alejandro Posadas; ArgentinaFil: Palermo, Mario. Hospital Nacional Prof. Dr. Alejandro Posadas; ArgentinaFil: Maskin, Bernardo. Hospital Nacional Prof. Dr. Alejandro Posadas; ArgentinaFil: Damiano, Alicia Ermelinda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Universidad Autónoma de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Crosstalk between ERα and NFκB transcription factors on E2 induced leptin expression in placental cells

Objectives: Leptin is a key hormone in placental physiology. It regulates trophoblast proliferation, inhibits apoptosis, stimulates protein synthesis, and regulates fetal growth and development. It plays an important role in reproduction mainly because it has been suggested to have function in the placenta during the gestation, where leptin and leptin receptors expression were detected. Previous results from our lab demonstrated that estradiol (E2) regulates leptin expression involving genomic and nongenomic effects. In the present work, we analysed the crosstalk between estrogen receptor alpha (ERa) and NFkB transcription factors on E2 induced leptin expression in human trophoblast cells. Methods: BeWo cells, cultured and human term placental explants were used. Western blot, immunocytochemistry, co-immunoprecipitation and transfection assays were carried out. Ethical review committee at the Alejandro Posadas National Hospital approved all procedures. Results: We found that E2 treatment significantly enhanced the NFkB member p65 expression both in BeWo cells and human term placental explants. Moreover E2 increased IkBa phosphorylation and NFkB transcriptional activity determined by reporter analysis. We also evaluated the localization of ERa and p65 NFkB subunit in BeWo cells by immunofluorescence assay. We found that both proteins are located in the cytoplasm and migrate to the nucleus when they are overexpressed. Besides ERa and p65 form a complex determined by co-immunoprecipitation, as previously seen. These findings suggest that the transcription factor NFkB, might be affecting estradiol leptin induction. Finally through transient transfection analysis we observed that the overexpression of RelA (p65) and HEGO (ERa) increases basal transcriptional activity of leptin promoter. Conclusion: These results suggest that leptin expression is tightly regulated and help to comprehend the mechanisms where E2 regulated leptin expression possibly involving the cooperation between ERa and NFkB transcription factors.Fil: Shanton, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Camisay, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pérez Pérez, Antonio. Universidad de Sevilla; EspañaFil: Maskin, Bernardo. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Casale, Roberto. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Sánchez Margalet, Victor. Universidad de Sevilla; EspañaFil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaInternational Federation of Placenta Associations Meeting y VIII Simposio Latinoamericano de Interacción Materno-Fetal y PlacentaBuenos AiresArgentinaInternational Federation of Placenta Association

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

INTRODUCTION: Continuous monitoring of bladder partial carbon dioxide tension (PCO(2)) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO(2). Our hypothesis was that bladder PCO(2), measured using saline tonometry, will be similar to ileal PCO(2 )during ischaemia and reperfusion. METHOD: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO(2 )gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO(2 )were measured using saline tonometry. RESULTS: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO(2 )gradients when compared with baseline values (all values in mmHg; bladder ΔPCO(2 )3 ± 3 versus 12 ± 5, ileal ΔPCO(2 )9 ± 5 versus 29 ± 16, mixed venous–arterial PCO(2 )5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO(2 )4 ± 2 versus 14 ± 4; P < 0.05 versus basal for all). After blood reinfusion, PCO(2 )gradients returned to basal values except for bladder ΔPCO(2), which remained at ischaemic levels (13 ± 7 mmHg). CONCLUSION: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO(2 )might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO(2 )gradients occurred in gut mucosa. Moreover, the fact that ileal ΔPCO(2 )was greater than the mesenteric venous–arterial PCO(2 )suggests that tonometrically measured PCO(2 )reflects mucosal rather than transmural PCO(2). Ileal ΔPCO(2 )appears to be the more sensitive marker of ischaemia

Effects of levosimendan and dobutamine in experimental acute endotoxemia : A preliminary controlled study

Objective: To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO2) and prevents intramucosal acidosis in septic shock. Design: Prospective, controlled experimental study. Setting: University-based research laboratory. Subjects: Nineteen anesthetized, mechanically ventilated sheep. Interventions: Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. Measurements and main results: After endotoxin administration, systemic and intestinal DO 2 decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO2 difference (∆PCO2) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO 2 was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO 2 decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ∆PCO 2 increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO 2 (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ∆PCO2 (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions: Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.Facultad de Ciencias Médica

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

INTRODUCTION: Increased intramucosal–arterial carbon dioxide tension (PCO(2)) difference (ΔPCO(2)) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ΔPCO(2). METHODS: In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO(2 )by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 μg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. RESULTS: In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ΔPCO(2 )increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ΔPCO(2 )(5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both). CONCLUSIONS: In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

Introduction: Continuous monitoring of bladder partial carbon dioxide tension (PCO₂) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO₂. Our hypothesis was that bladder PCO₂, measured using saline tonometry, will be similar to ileal PCO₂ during ischaemia and reperfusion. Method: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO₂ gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO2 were measured using saline tonometry. Results: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO₂ gradients when compared with baseline values (all values in mmHg; bladder ∆PCO₂ 3 ± 3 versus 12 ± 5, ileal ∆PCO₂ 9 ± 5 versus 29 ± 16, mixed venous–arterial PCO₂ 5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO₂ 4 ± 2 versus 14 ± 4; P &lt; 0.05 versus basal for all). After blood reinfusion, PCO₂ gradients returned to basal values except for bladder ∆PCO₂, which remained at ischaemic levels (13 ± 7 mmHg). Conclusion: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO₂ might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO₂gradients occurred in gut mucosa. Moreover, the fact that ileal ∆PCO₂ was greater than the mesenteric venous–arterial PCO₂ suggests that tonometrically measured PCO₂ reflects mucosal rather than transmural PCO₂. Ileal ∆PCO₂ appears to be the more sensitive marker of ischaemia.Facultad de Ciencias Médica

Effects of levosimendan and dobutamine in experimental acute endotoxemia : A preliminary controlled study

Objective: To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO2) and prevents intramucosal acidosis in septic shock. Design: Prospective, controlled experimental study. Setting: University-based research laboratory. Subjects: Nineteen anesthetized, mechanically ventilated sheep. Interventions: Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. Measurements and main results: After endotoxin administration, systemic and intestinal DO 2 decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO2 difference (∆PCO2) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO 2 was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO 2 decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ∆PCO 2 increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO 2 (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ∆PCO2 (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions: Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.Facultad de Ciencias Médica

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

Introduction Increased intramucosal–arterial carbon dioxide tension (PCO₂) difference (∆PCO₂) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ∆PCO₂. Methods In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO₂ by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 µg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. Results In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ∆PCO₂ increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ∆PCO2 (5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both). Conclusions In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations.Facultad de Ciencias Médica