Search

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19–16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE. [ABSTRACT FROM AUTHOR]

BACKGROUND Arsenic (As) is a serious water pollution problem in the world. In Argentina, it is related to old volcanic activities; for example, the western region of Santa Fe State has concentrations higher than 0.1 mgAs L−1. In this work, a green, sensitive method was used to determine As concentration, and its removal using chitosan in bed columns was studied. Mathematical models were used to explain sorption, and the process was optimized using statistical methods. RESULTS: Arsenic quantification was realized with a bespoke modification of the As molybdenum blue method (detection limit = 0.0048 mg L−1, quantification limit = 0.0145 mg L−1). Chitosan molar mass, pHZPC and deacetylation degree were 350 ± 10 kDa, 6.3% and 76.2%, respectively. A maximum of 68.5% was obtained for As(V) removal at optimum conditions. Raising the bed column height produced an increment in breakthrough times, and the sorption process was favoured using low flow rates. Salinity, phosphate and nitrate concentration reductions were 60%, 50% and 70%, respectively. CONCLUSIONS: Sorption studies have been carried out on groundwater, using columns packed with chitosan for arsenic removal. The process was optimized by a factorial design. Elution profiles were adjusted adequately with mathematical models. The modified analytical technique for arsenic quantification applied in groundwater, was successful. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Local thyrotropin-releasing hormone (TRH) may be involved in cardiac pathophysiology, but its role in left ventricular hypertrophy (LVH) is still unknown. We studied whether local TRH is involved in LVH of spontaneously hypertensive rats (SHR) by investigating TRH expression and its long-term inhibition by interference RNA (TRH-iRNA) during LVH development at 2 stages (prehypertrophy and hypertrophy). SHR and their control rats (WKY) were compared. Cardiac hypertrophy was expressed as heart/total body weight (HW/BW) ratio. TRH content (radioimmuno assay), preproTRH, TRH receptor type I, brain natriuretic peptide (BNP), and collagen mRNA expressions (real-time polymerase chain reaction) were measured. For long-term inhibition of TRH, TRH-iRNA was injected into the left ventricle (LV) wall for 8 weeks. Hearts were processed for morphometric studies and immunohistochemical analysis using antibodies against α-smooth muscle actin and collagen type III. LV preproTRH-mRNA abundance was similar in both strains at 7 weeks of age. At the hypertrophic stage (18 weeks old), however, there was a 15-fold increase in SHR versus WKY, consistent with a significant increase in tripeptide levels and the expression of its receptor. Specific LV-TRH inhibition at the prehypertensive stage with TRH-iRNA, which decreased >50% preproTRH expression and tripeptide levels, prevented LVH development as shown by the normal HW/BW ratio observed in TRH-iRNA-treated SHR. In addition, TRH-iRNA impeded the increase in BNP and type III collagen expressions and prevented the increase in cardiomyocyte diameter evident in mismatch iRNA-treated adult SHR. These results show for the first time that the cardiac TRH system is involved in the development of LVH in SHR. [ABSTRACT FROM AUTHOR]

We explored peroxisome proliferator-activated receptor-γ co-activator 1α gene (PPARGC1A), peroxisome proliferator-activated receptor-γ gene (PPARG), and transcription factor A mitochondrial gene (Tfam) promoter DNA methylation in newborns between both extremes of abnormal fetal growth: Small (SGA) and large for gestational age (LGA) in relation to the mother's characteristics. We further sought for the association of rs9930506 variant at FTO gene and the promoter patterns of DNA methylation in the aforementioned genes, in relation to the offspring's birth weight. In a cross-sectional study, 88 healthy pregnant women and their babies were included. According to the offspring birth weight, there were 57 newborns with appropriate weight for gestational age (AGA), 17 SGA, and 14 LGA. After bisulphite treatment of umbilical cord genomic DNA, a real-time methylation-specific PCR was used to determine the promoter methylation status in selected CpGs. Promoter methylated DNA/unmethylated DNA ratio, expressed as mean ± s.e., was 0.82 ± 0.15 (45% of alleles) for PPARGC1A, and 0.0044 ± 0.0006 (0.4% of alleles) for Tfam. PPARG promoter was almost 100% methylated in all samples. In univariate analysis, there was no association among characteristics of the newborn and gene promoter methylation. None of the maternal features were related with the status of promoter methylation, except for a positive correlation between maternal BMI and PPARGC1A promoter methylation in umbilical cord (Pearson correlation coefficient r = 0.41, P = 0.0007). Finally, FTO rs9930506 AA homozygous in the LGA group showed decreased levels of methylated PPARGC1A in comparison with AG + GG genotypes and AGA and SGA infants. In conclusion, our findings suggest a potential role of promoter PPARGC1A methylation in metabolic programming.Obesity (2009) 17 5, 1032–1039. doi:10.1038/oby.2008.605 [ABSTRACT FROM AUTHOR]

Selective oxidation of galacturonic acid residues of apple pectin by CrVI affords CO2/HCO2H, oxidized pectin, and CrIII as final redox products. The reaction shows first-order kinetics in [pectin], [CrVI], and [H+], at fixed ionic strength and temperature. Kinetic studies show that the redox reaction proceeds through a mechanism combining CrVI → CrIV → CrII and CrVI → CrIV → CrIII pathways. The mechanism is supported by the observation of free radicals, CrO22+ (the formation of which implies involvement of CrII and CrIV) and CrV (formed in monoelectronic redox processes) as reaction intermediates. The reduction of CrIV and CrV by pectin was independently studied and found to occur more than 103 times faster than pectin + CrVI reaction, in acid medium. At pH 3–5, apple pectin + CrVI redox reaction is slow, oxo-chromate(V)–pectin species stabilize and remain in solution during several hours. The present results show that these abundant and ubiquitous components of the cell walls of all land plants are able to reduce CrIV–VI or stabilize high-valent chromium depending on pH. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor-α (TNF-α) has been associated with obesity, obesity-related hypertension, and metabolic syndrome. We investigated the possible contribution of the G-308A TNF-α mutant to explain variables of the metabolic syndrome. Methods: Data and blood samples were used from the 175 adolescents that satisfied the criterion of having systolic or diastolic blood pressures (BP) more than the 80th or less than the 20th percentiles, out of a cross-sectional, population-based study of 934 high school students. Genotyping for the polymorphism was performed by polymerase chain reaction-based restriction fragment length polymorphism analysis. Results: In univariate analysis, we found that there was no difference between A allele carriers and noncarriers in most of the clinical characteristics of the metabolic syndrome such as body mass index (BMI), waist-to-hip ratio, plasma leptin levels, total cholesterol, HDL- and LDL-cholesterol, triglycerides, plasma fasting glucose, insulin, and homocysteine levels. However, we found a significantly (P = .015) higher age- and sex-adjusted systolic BP (Z score) in the A allele carriers, and A allele carriers also showed an elevated homeostasis model assessment of insulin resistance (HOMA) index with respect to noncarriers. Logistic regression analysis indicates that A allele carriers had a 2.8-fold higher probability of being hypertensive independent of BMI, waist-to-hip ratio, and HOMA index. Conclusions: In this report we found a positive association between the G-308A TNF-α variant and systolic arterial BP Z score and HOMA index in adolescents harboring features of metabolic syndrome. Therefore, the A allele may predispose to hypertension and insulin resistance in youth. [Copyright &y& Elsevier]

Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, β-myosin heavy chain, Bax-to-Bcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and β-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data "in vitro" using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target., (Copyright © 2014 the American Physiological Society.)

We recently showed that diencephalic TRH may mediate the central leptin-induced pressor effect. Here, to study the role of TRH in obesity-induced hypertension (OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP) increased in HFD animals. Plasma leptin was correlated with peritoneal adipose tissue. Then, we treated OIH animals with an antisense oligodeoxynucleotide and small interfering (si)RNA against the prepro-TRH. Antisense significantly decreased diencephalic TRH content and SABP at 24 and 48 h posttreatment. Similar effects were observed with siRNA against prepro-TRH but for up to 4 wk. Conversely, vehicle, an inverted antisense sequence and siRNA against green fluorescence protein, produced no changes. SABP decrease seems to be owing to an inhibition of the obesity-enhanced sympathetic outflow but not to an alteration in thyroid status. Using a simple OIH model we demonstrated, for the first time, that central TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity. Thus the TRH-leptin interaction may contribute to the strong association between hypertension and obesity.

Background: Tumor necrosis factor-alpha (TNF-alpha) has been associated with obesity, obesity-related hypertension, and metabolic syndrome. We investigated the possible contribution of the G-308A TNF-alpha mutant to explain variables of the metabolic syndrome., Methods: Data and blood samples were used from the 175 adolescents that satisfied the criterion of having systolic or diastolic blood pressures (BP) more than the 80th or less than the 20th percentiles, out of a cross-sectional, population-based study of 934 high school students. Genotyping for the polymorphism was performed by polymerase chain reaction-based restriction fragment length polymorphism analysis., Results: In univariate analysis, we found that there was no difference between A allele carriers and noncarriers in most of the clinical characteristics of the metabolic syndrome such as body mass index (BMI), waist-to-hip ratio, plasma leptin levels, total cholesterol, HDL- and LDL-cholesterol, triglycerides, plasma fasting glucose, insulin, and homocysteine levels. However, we found a significantly (P = .015) higher age- and sex-adjusted systolic BP (Z score) in the A allele carriers, and A allele carriers also showed an elevated homeostasis model assessment of insulin resistance (HOMA) index with respect to noncarriers. Logistic regression analysis indicates that A allele carriers had a 2.8-fold higher probability of being hypertensive independent of BMI, waist-to-hip ratio, and HOMA index., Conclusions: In this report we found a positive association between the G-308A TNF-alpha variant and systolic arterial BP Z score and HOMA index in adolescents harboring features of metabolic syndrome. Therefore, the A allele may predispose to hypertension and insulin resistance in youth.