The document describes a study examining the effects of polyphenol-rich food supplementation on ductus arteriosus blood flow and markers of oxidative stress and inflammation in pregnant sheep. The study found that supplementing pregnant sheep with polyphenol-rich foods for 14 days induced constriction of the ductus arteriosus in fetuses, accompanied by increases in markers of oxidative stress like protein carbonyls and antioxidant enzymes, and decreases in inflammatory nitric oxide. Ductal blood flow parameters correlated with changes in these oxidative stress and inflammatory markers. The results suggest polyphenol intake in late pregnancy may induce fetal duct constriction through anti-inflammatory effects and involvement of oxidative stress.
1) The study tested the hypothesis that maternal ingestion of green tea in late pregnancy causes fetal ductal constriction by inhibiting prostaglandins. 2) Echocardiography of fetal lambs exposed to green tea in utero showed signs of ductal constriction compared to controls. 3) Autopsies found dilated and hypertrophic right ventricles in lambs exposed to green tea, and histological analysis found thicker ductal walls in these lambs.
Effect of polyphenols on the intestinal and placental transport of somegisa_legal
This document reviews the effect of polyphenols on the intestinal and placental transport of some bioactive compounds. It discusses how different classes of polyphenols can affect the transport of organic cations, glucose, thiamine, and folic acid across intestinal and placental barriers. The effects of polyphenols can vary depending on factors like acute vs chronic exposure, and how polyphenols interact when consumed together compared to individually. While most data is from in vitro studies, the review raises concerns about how polyphenol consumption may impact the bioavailability of other compounds.
This study examined the relationship between maternal consumption of polyphenol-rich foods late in pregnancy and fetal ductus arteriosus flow dynamics. Doppler ultrasound was used to compare ductal velocities and right-to-left ventricular dimensions in 102 fetuses exposed to high maternal polyphenol intake versus 41 unexposed fetuses. Exposed fetuses had higher ductal velocities and right-to-left ventricular ratios, suggesting maternal polyphenol-rich food intake may influence fetal ductal dynamics by inhibiting prostaglandin synthesis, similarly to non-steroidal anti-inflammatory drugs. As polyphenol-rich foods are commonly consumed during pregnancy, their effects on the fetal ductus warrant further consideration.
This study tested the hypothesis that restricting a pregnant woman's intake of polyphenol-rich foods for at least two weeks improves ductus arteriosus blood flow dynamics in healthy third-trimester fetuses, as was previously shown in fetuses with ductal constriction. 46 pregnant women restricted their polyphenol intake from an average of 1277 mg/day to 126 mg/day. Their fetuses showed significant decreases in ductal velocities and RV/LV ratio, and an increase in ductal pulsatility index. A control group of 26 women showed no significant changes. The study suggests that reducing maternal polyphenol intake improves fetal ductal hemodynamics in normal pregnancies.
This document provides documentation for the USDA Database for Flavonoid Content of Selected Foods, Release 2.1. It summarizes the procedures used to update the database with 168 new foods and additional compounds for some existing foods. Analytical values were obtained from USDA analysis of foods as well as from literature. Values are provided for 26 common flavonoid compounds in five subclasses. The database is presented in tables listing nutritional values for flavonoids in 385 foods, and is intended to be a resource for researchers, nutritionists and consumers.
This document summarizes an open clinical trial that tested the hypothesis that restricting polyphenol-rich foods (PRF) in maternal diets during the third trimester can reverse fetal ductal constriction (DC). The study found that 96% of fetuses with DC showed complete reversal after their mothers discontinued PRF for at least 3 weeks. Maternal PRF intake decreased significantly, while ductal blood flow parameters like velocity and pulsatility index normalized. In a control group where no dietary changes were made, ductal measurements did not significantly change. The results support that maternal PRF intake during pregnancy can cause DC through anti-inflammatory effects, and that restricting these foods can reverse the condition.
This study aimed to validate a food frequency questionnaire (FFQ) used in the Norwegian Mother and Child Cohort Study (MoBa) to assess fruit, vegetable, and tea intake during pregnancy. The FFQ estimates were compared to urinary flavonoid levels, plasma carotenoid levels, and a 4-day weighed food diary (FD) completed by 119 pregnant women. Correlations were found between the FFQ and biomarkers for various food groups. Using the triangular method with two biomarkers, validity coefficients of 0.65 and 0.59 were calculated for the FFQ's ability to estimate citrus fruit/juice and cooked vegetable intake respectively. The study shows the MoBa FFQ can be used to estimate and rank
This study developed and validated a food frequency questionnaire (FFQ) to assess intake of polyphenol-rich foods in pregnant women in Brazil. 120 pregnant women participated in nutritional interviews on two occasions and provided urine samples. The FFQ included 52 foods and was compared to 24-hour recalls, 3-day food diaries, and urinary polyphenol levels. Analysis showed high reproducibility between the two FFQ administrations. Moderate to high correlations were found between the dietary assessment methods. A low but significant correlation was observed between the FFQ and urinary polyphenol levels. The study concluded that the FFQ is a valid tool for quantifying intake of total polyphenols in pregnant women.
1) The study tested the hypothesis that maternal ingestion of green tea in late pregnancy causes fetal ductal constriction by inhibiting prostaglandins. 2) Echocardiography of fetal lambs exposed to green tea in utero showed signs of ductal constriction compared to controls. 3) Autopsies found dilated and hypertrophic right ventricles in lambs exposed to green tea, and histological analysis found thicker ductal walls in these lambs.
Effect of polyphenols on the intestinal and placental transport of somegisa_legal
This document reviews the effect of polyphenols on the intestinal and placental transport of some bioactive compounds. It discusses how different classes of polyphenols can affect the transport of organic cations, glucose, thiamine, and folic acid across intestinal and placental barriers. The effects of polyphenols can vary depending on factors like acute vs chronic exposure, and how polyphenols interact when consumed together compared to individually. While most data is from in vitro studies, the review raises concerns about how polyphenol consumption may impact the bioavailability of other compounds.
This study examined the relationship between maternal consumption of polyphenol-rich foods late in pregnancy and fetal ductus arteriosus flow dynamics. Doppler ultrasound was used to compare ductal velocities and right-to-left ventricular dimensions in 102 fetuses exposed to high maternal polyphenol intake versus 41 unexposed fetuses. Exposed fetuses had higher ductal velocities and right-to-left ventricular ratios, suggesting maternal polyphenol-rich food intake may influence fetal ductal dynamics by inhibiting prostaglandin synthesis, similarly to non-steroidal anti-inflammatory drugs. As polyphenol-rich foods are commonly consumed during pregnancy, their effects on the fetal ductus warrant further consideration.
This study tested the hypothesis that restricting a pregnant woman's intake of polyphenol-rich foods for at least two weeks improves ductus arteriosus blood flow dynamics in healthy third-trimester fetuses, as was previously shown in fetuses with ductal constriction. 46 pregnant women restricted their polyphenol intake from an average of 1277 mg/day to 126 mg/day. Their fetuses showed significant decreases in ductal velocities and RV/LV ratio, and an increase in ductal pulsatility index. A control group of 26 women showed no significant changes. The study suggests that reducing maternal polyphenol intake improves fetal ductal hemodynamics in normal pregnancies.
This document provides documentation for the USDA Database for Flavonoid Content of Selected Foods, Release 2.1. It summarizes the procedures used to update the database with 168 new foods and additional compounds for some existing foods. Analytical values were obtained from USDA analysis of foods as well as from literature. Values are provided for 26 common flavonoid compounds in five subclasses. The database is presented in tables listing nutritional values for flavonoids in 385 foods, and is intended to be a resource for researchers, nutritionists and consumers.
This document summarizes an open clinical trial that tested the hypothesis that restricting polyphenol-rich foods (PRF) in maternal diets during the third trimester can reverse fetal ductal constriction (DC). The study found that 96% of fetuses with DC showed complete reversal after their mothers discontinued PRF for at least 3 weeks. Maternal PRF intake decreased significantly, while ductal blood flow parameters like velocity and pulsatility index normalized. In a control group where no dietary changes were made, ductal measurements did not significantly change. The results support that maternal PRF intake during pregnancy can cause DC through anti-inflammatory effects, and that restricting these foods can reverse the condition.
This study aimed to validate a food frequency questionnaire (FFQ) used in the Norwegian Mother and Child Cohort Study (MoBa) to assess fruit, vegetable, and tea intake during pregnancy. The FFQ estimates were compared to urinary flavonoid levels, plasma carotenoid levels, and a 4-day weighed food diary (FD) completed by 119 pregnant women. Correlations were found between the FFQ and biomarkers for various food groups. Using the triangular method with two biomarkers, validity coefficients of 0.65 and 0.59 were calculated for the FFQ's ability to estimate citrus fruit/juice and cooked vegetable intake respectively. The study shows the MoBa FFQ can be used to estimate and rank
This study developed and validated a food frequency questionnaire (FFQ) to assess intake of polyphenol-rich foods in pregnant women in Brazil. 120 pregnant women participated in nutritional interviews on two occasions and provided urine samples. The FFQ included 52 foods and was compared to 24-hour recalls, 3-day food diaries, and urinary polyphenol levels. Analysis showed high reproducibility between the two FFQ administrations. Moderate to high correlations were found between the dietary assessment methods. A low but significant correlation was observed between the FFQ and urinary polyphenol levels. The study concluded that the FFQ is a valid tool for quantifying intake of total polyphenols in pregnant women.
1) The study examined the effect of probiotics in preventing necrotizing enterocolitis (NEC) in preterm neonates compared to a control group.
2) 115 preterm infants weighing 750-1500g or less than 32 weeks gestation received probiotics or did not (control). The probiotic group had significantly lower incidence of NEC and fewer cases of elevated C-reactive protein.
3) However, there were no significant differences between the groups in duration of oxygen therapy, total parenteral nutrition, time to full feeding, or length of hospital stay. The study results suggest probiotics have a protective effect against NEC in preterm infants.
1. The document discusses extended cycle oral contraceptives that provide contraception for 84 days by suppressing ovulation through a combination of ethinyl estradiol and levonorgestrel, followed by 7 days of placebo or low-dose estrogen pills.
2. Clinical trials showed that extended cycle pills were as effective at preventing pregnancy as conventional 28-day pills, with similar safety profiles. Adverse effects were mild and consistent with other combined oral contraceptives.
3. The extended cycle regimen was found to be over 99% effective at preventing pregnancy when taken correctly, and resulted in less frequent bleeding and spotting compared to a 28-day regimen.
Adequacy of Enteral Nutritional Therapy Offered to Patients in an Intensive C...asclepiuspdfs
The document summarizes a study that evaluated the nutritional status and adequacy of enteral nutritional therapy (ENT) provided to patients in an intensive care unit (ICU) in Brazil. The study found that most patients were elderly and malnourished or at nutritional risk upon admission. However, the average calorie and protein requirements were not met, with only 40% of calorie and protein needs being adequately provided. The main reasons for inadequate ENT were delays initiating enteral tube feeding and fasting periods for clinical procedures. As a result, over 90 liters of prescribed enteral nutrition were wasted. The study concludes that malnutrition, delays starting ENT, and fasting may increase mortality risk for critically ill ICU patients.
This document summarizes a study that assessed the impact of supplementing the diets of severely malnourished children in Burkina Faso with Moringa oleifera leaf powder. 110 children aged 6-59 months were randomly assigned to two groups. Both groups received standard nutritional care, but one group received an additional 10g per day of Moringa leaf powder. Children receiving the Moringa supplement had higher average weight gain, a quicker recovery rate, but no significant difference in hemoglobin levels. The Moringa supplementation was found to be effective and safe in improving the nutritional recovery of severely malnourished children.
In this study, we focused on the effect of β-glucan supplementation of children with chronic respiratory problems. We measured the levels of cortisol, salivary IgE and cotinine in 56 children and evaluated the effect of 30 day supplementation with 100 mg/day oral dose of yeast-derived β-glucan. Our results showed strong decrease of cotinine and cortisol levels in saliva of β-glucan-supplemented children. The increase of total salivary IgE levels in both groups was not statistically significant. The positive effects of complex curative treatment using β-glucan were accompanied by increased physical endurance and by significant reduction of negative clinical problems of affected children.
This document is a manuscript describing a study on the effects of maternal consumption of polyphenol-rich foods on fetal ductus arteriosus constriction in pregnant sheep. The study found that 2 weeks of polyphenol supplementation in pregnant sheep resulted in ductus arteriosus constriction in fetuses, accompanied by increased polyphenol excretion and decreased inflammatory markers in the mothers. It also observed changes in oxidative stress biomarkers in the mothers, despite some markers of oxidative damage being lower after supplementation. The results suggest that high maternal polyphenol intake can induce fetal ductal constriction through anti-inflammatory effects, and oxidative stress may be involved.
This study compared the effects of beractant and poractant surfactant treatments in 58 premature infants with respiratory distress syndrome (RDS). The main findings were:
1) Infants who received poractant had a lower oxygen requirement (FiO2) during the first 48 hours compared to infants who received beractant.
2) Infants who received poractant also had fewer cases of patent ductus arteriosus (PDA) than infants who received beractant.
3) There was no significant difference between the groups in factors like time to first extubation, total intubation time, or rates of bronchopulmonary dysplasia.
Effects of Daily Consumption of Synbiotic Bread on Insulin Metabolism and Ser...Haleh Hadaegh
1) This randomized controlled trial examined the effects of consuming synbiotic, probiotic, or control bread on insulin metabolism and inflammation markers in 81 diabetic patients over 8 weeks.
2) Patients who consumed synbiotic bread had a significant reduction in insulin levels, insulin resistance scores, and beta-cell function compared to the probiotic and control bread groups.
3) The synbiotic bread, containing Lactobacillus sporogenes and inulin, improved insulin metabolism but did not significantly affect other measures like blood glucose, insulin sensitivity, or CRP levels compared to the other breads.
This study evaluated the self-reported effects of dairy products on symptoms of Crohn's disease (CD) in 165 patients in New Zealand. The key findings were:
1) Dairy products had no effect on symptoms for most patients (67.3%), but dairy products high in fat like cream and ice cream were most likely to worsen symptoms.
2) Disease activity status (active vs quiescent CD) did not influence responses to dairy, but colonic inflammation was more often associated with adverse effects than ileal involvement.
3) Symptom worsening from dairy was highly individual, influenced more by fat content and disease location than by lactose or disease activity status.
This document summarizes three research projects related to blood pressure in vegetarians from an epidemiological and physiological perspective:
1. A cross-sectional study comparing blood pressure, diet, and lifestyle between Seventh-day Adventists and Mormons through questionnaires, diet records, and health screenings.
2. A laboratory study identifying possible differences in blood pressure control mechanisms between vegetarian Adventists and omnivorous Mormons through physiological stresses and measures of pressor and depressor substances.
3. A short-term dietary intervention study feeding a vegetarian diet to normotensive subjects and monitoring changes in blood pressure and biochemical/physiological parameters over 14 weeks.
This document summarizes research on the effects of dietary polyphenols on reproductive health and early development. It discusses the classification, sources, pharmacokinetics and molecular targets of polyphenols. While many studies show polyphenols have beneficial effects by reducing oxidative stress and inflammation, some evidence suggests high polyphenol intake could negatively impact fertility, fetal health and nutrient availability. More research is needed to understand the risks and benefits of polyphenol consumption during pregnancy.
The EAT study was a randomized controlled trial that evaluated whether introducing common allergenic foods like peanut, egg, and milk earlier would prevent food allergies in breastfed infants compared to exclusive breastfeeding for 6 months. Over 1300 infants were randomly assigned at 3 months of age to either the early introduction group, which introduced the foods between 3-6 months, or the standard introduction group. The primary outcome was food allergy to one of the foods between 1-3 years of age. The intention-to-treat analysis found no significant difference in food allergy rates between the groups. However, per-protocol and consumption-based analyses raised the possibility that prevention may be dose-dependent.
Early total enteral feeding in stable preterm infants a systematic review and...dineshdharel13
In conclusion, it seems feasible and safe to start total enteral feeding in stable VLBW infants born with birth weight greater than 1000–1200g. This approach can reduce the need of intravenous fluid or PN and its adverse consequences as well as decrease the length of hospital stay for these infants. A larger randomized trial is needed to ensure ETEF is not associated with increased risk of NEC in stable preterm infants with birth weight greater than 1000g and gestational age greater than 28 weeks. Furthermore, there is a need to explore whether ETEF regimen is feasible in extremely low birth weight infants.
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is an open access international journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
4th july 2020 daily global regional and local rice e newsletterRiceplus Magazine
Scientists from ICRISAT and collaborators have uncovered a molecular mechanism controlling male fertility in pigeonpea crops. They found that temperature affects whether plants are male fertile or sterile - below 24°C they are fertile, above they are sterile. Applying plant hormones can also reverse sterility at some temperatures. This finding could enable developing improved hybrid pigeonpea varieties using cheaper two-line hybrid technology instead of three-line technology. The researchers also forecast a record global cereal production in 2020, with the stock-to-use ratio reaching a twenty-year high.
Fibrinogen concentration and thrombin levels in pregnant women in nnewi, anam...Alexander Decker
This study examined fibrinogen concentration and thrombin time (TT) levels in 195 pregnant women in Nigeria compared to 150 non-pregnant women. Fibrinogen concentration and TT were significantly higher in pregnant women compared to non-pregnant women. Fibrinogen concentration and TT levels increased with each trimester of pregnancy and were highest in the third trimester. The increases in coagulation factors during pregnancy are likely due to hormonal changes and inflammation of pregnancy to prepare the body for potential blood loss during childbirth. Baseline measurements of these coagulation factors during antenatal visits could help detect any abnormalities.
This study aimed to evaluate the reproducibility and validity of a food frequency questionnaire (FFQ) to assess intake of polyphenol-rich foods in pregnant women in Brazil. 120 pregnant women participated in two interviews where they completed the FFQ and 24-hour dietary recalls. 93 women also completed 3-day food diaries and provided urine samples. The FFQ showed moderate to high correlations with the 24-hour recalls and food diaries. The correlation between the FFQ and urinary polyphenol levels was low but significant. The study concluded that the FFQ is reproducible and valid for quantifying intake of total polyphenols in pregnant women.
This study validated a food frequency questionnaire (FFQ) used to measure fruit, vegetable, and tea intake in pregnant women in Norway. The FFQ estimates were compared to biomarkers (urinary flavonoids and plasma carotenoids) and a 4-day weighed food diary. Correlations between the FFQ and biomarkers provided evidence that the FFQ could reliably estimate intake of certain foods, with validity coefficients of 0.65 for citrus fruit/juice and 0.59 for cooked vegetables. Overall, the validation study demonstrated the FFQ's ability to estimate fruit, juice, vegetable and tea intake in pregnant Norwegian women.
Effect of polyphenols on the intestinal and placental 2012gisa_legal
This document summarizes a research article that studied the effect of polyphenols on the intestinal and placental transport of some bioactive compounds. Some key findings of the research article include:
1) Different classes of polyphenols can affect the transport of organic cations, glucose, thiamine, and folic acid at the intestinal and placental barriers.
2) Within the same phenolic family, different compounds may have opposite effects on the transport of certain molecules.
3) Acute and chronic exposures to polyphenols do not always produce the same results, so care is needed when extrapolating findings.
4) The combined effect of polyphenols may differ from the individual effects
This study examined the effects of restricting polyphenol-rich foods in the diets of pregnant women in their third trimester on fetal ductal flow dynamics. 46 pregnant women consuming high levels of polyphenols were asked to restrict these foods for 2 weeks or more. Their fetuses showed significant decreases in ductal blood flow velocities and right ventricular size, as well as an increase in ductal pulsatility index. A control group of 26 women showed no significant changes. The study suggests that restricting maternal polyphenol intake in the third trimester can improve fetal ductal flow and right heart dimensions in normal pregnancies, as seen previously in cases of ductal constriction.
1) Twelve fetal lambs were studied before and after their mothers were given either green tea or water for one week. 2) Echocardiography after one week showed signs of ductal constriction in all lambs whose mothers drank green tea, including increased ductal velocities and right ventricular enlargement. 3) Autopsies also showed enlarged and thickened right ventricles in lambs exposed to green tea compared to controls. Histology found the ductal medial avascular zone was significantly thicker in green tea lambs versus controls, indicating ductal constriction.
O documento lista alimentos ricos em polifenóis como uvas, erva-mate, chás, chocolate preto, frutas cítricas e hortaliças. Estudos mostram que o consumo desses alimentos na gravidez pode afetar o fluxo do ducto arterial fetal. Um questionário de frequência alimentar foi desenvolvido para avaliar o consumo de alimentos ricos em polifenóis por grávidas.
1) The study examined the effect of probiotics in preventing necrotizing enterocolitis (NEC) in preterm neonates compared to a control group.
2) 115 preterm infants weighing 750-1500g or less than 32 weeks gestation received probiotics or did not (control). The probiotic group had significantly lower incidence of NEC and fewer cases of elevated C-reactive protein.
3) However, there were no significant differences between the groups in duration of oxygen therapy, total parenteral nutrition, time to full feeding, or length of hospital stay. The study results suggest probiotics have a protective effect against NEC in preterm infants.
1. The document discusses extended cycle oral contraceptives that provide contraception for 84 days by suppressing ovulation through a combination of ethinyl estradiol and levonorgestrel, followed by 7 days of placebo or low-dose estrogen pills.
2. Clinical trials showed that extended cycle pills were as effective at preventing pregnancy as conventional 28-day pills, with similar safety profiles. Adverse effects were mild and consistent with other combined oral contraceptives.
3. The extended cycle regimen was found to be over 99% effective at preventing pregnancy when taken correctly, and resulted in less frequent bleeding and spotting compared to a 28-day regimen.
Adequacy of Enteral Nutritional Therapy Offered to Patients in an Intensive C...asclepiuspdfs
The document summarizes a study that evaluated the nutritional status and adequacy of enteral nutritional therapy (ENT) provided to patients in an intensive care unit (ICU) in Brazil. The study found that most patients were elderly and malnourished or at nutritional risk upon admission. However, the average calorie and protein requirements were not met, with only 40% of calorie and protein needs being adequately provided. The main reasons for inadequate ENT were delays initiating enteral tube feeding and fasting periods for clinical procedures. As a result, over 90 liters of prescribed enteral nutrition were wasted. The study concludes that malnutrition, delays starting ENT, and fasting may increase mortality risk for critically ill ICU patients.
This document summarizes a study that assessed the impact of supplementing the diets of severely malnourished children in Burkina Faso with Moringa oleifera leaf powder. 110 children aged 6-59 months were randomly assigned to two groups. Both groups received standard nutritional care, but one group received an additional 10g per day of Moringa leaf powder. Children receiving the Moringa supplement had higher average weight gain, a quicker recovery rate, but no significant difference in hemoglobin levels. The Moringa supplementation was found to be effective and safe in improving the nutritional recovery of severely malnourished children.
In this study, we focused on the effect of β-glucan supplementation of children with chronic respiratory problems. We measured the levels of cortisol, salivary IgE and cotinine in 56 children and evaluated the effect of 30 day supplementation with 100 mg/day oral dose of yeast-derived β-glucan. Our results showed strong decrease of cotinine and cortisol levels in saliva of β-glucan-supplemented children. The increase of total salivary IgE levels in both groups was not statistically significant. The positive effects of complex curative treatment using β-glucan were accompanied by increased physical endurance and by significant reduction of negative clinical problems of affected children.
This document is a manuscript describing a study on the effects of maternal consumption of polyphenol-rich foods on fetal ductus arteriosus constriction in pregnant sheep. The study found that 2 weeks of polyphenol supplementation in pregnant sheep resulted in ductus arteriosus constriction in fetuses, accompanied by increased polyphenol excretion and decreased inflammatory markers in the mothers. It also observed changes in oxidative stress biomarkers in the mothers, despite some markers of oxidative damage being lower after supplementation. The results suggest that high maternal polyphenol intake can induce fetal ductal constriction through anti-inflammatory effects, and oxidative stress may be involved.
This study compared the effects of beractant and poractant surfactant treatments in 58 premature infants with respiratory distress syndrome (RDS). The main findings were:
1) Infants who received poractant had a lower oxygen requirement (FiO2) during the first 48 hours compared to infants who received beractant.
2) Infants who received poractant also had fewer cases of patent ductus arteriosus (PDA) than infants who received beractant.
3) There was no significant difference between the groups in factors like time to first extubation, total intubation time, or rates of bronchopulmonary dysplasia.
Effects of Daily Consumption of Synbiotic Bread on Insulin Metabolism and Ser...Haleh Hadaegh
1) This randomized controlled trial examined the effects of consuming synbiotic, probiotic, or control bread on insulin metabolism and inflammation markers in 81 diabetic patients over 8 weeks.
2) Patients who consumed synbiotic bread had a significant reduction in insulin levels, insulin resistance scores, and beta-cell function compared to the probiotic and control bread groups.
3) The synbiotic bread, containing Lactobacillus sporogenes and inulin, improved insulin metabolism but did not significantly affect other measures like blood glucose, insulin sensitivity, or CRP levels compared to the other breads.
This study evaluated the self-reported effects of dairy products on symptoms of Crohn's disease (CD) in 165 patients in New Zealand. The key findings were:
1) Dairy products had no effect on symptoms for most patients (67.3%), but dairy products high in fat like cream and ice cream were most likely to worsen symptoms.
2) Disease activity status (active vs quiescent CD) did not influence responses to dairy, but colonic inflammation was more often associated with adverse effects than ileal involvement.
3) Symptom worsening from dairy was highly individual, influenced more by fat content and disease location than by lactose or disease activity status.
This document summarizes three research projects related to blood pressure in vegetarians from an epidemiological and physiological perspective:
1. A cross-sectional study comparing blood pressure, diet, and lifestyle between Seventh-day Adventists and Mormons through questionnaires, diet records, and health screenings.
2. A laboratory study identifying possible differences in blood pressure control mechanisms between vegetarian Adventists and omnivorous Mormons through physiological stresses and measures of pressor and depressor substances.
3. A short-term dietary intervention study feeding a vegetarian diet to normotensive subjects and monitoring changes in blood pressure and biochemical/physiological parameters over 14 weeks.
This document summarizes research on the effects of dietary polyphenols on reproductive health and early development. It discusses the classification, sources, pharmacokinetics and molecular targets of polyphenols. While many studies show polyphenols have beneficial effects by reducing oxidative stress and inflammation, some evidence suggests high polyphenol intake could negatively impact fertility, fetal health and nutrient availability. More research is needed to understand the risks and benefits of polyphenol consumption during pregnancy.
The EAT study was a randomized controlled trial that evaluated whether introducing common allergenic foods like peanut, egg, and milk earlier would prevent food allergies in breastfed infants compared to exclusive breastfeeding for 6 months. Over 1300 infants were randomly assigned at 3 months of age to either the early introduction group, which introduced the foods between 3-6 months, or the standard introduction group. The primary outcome was food allergy to one of the foods between 1-3 years of age. The intention-to-treat analysis found no significant difference in food allergy rates between the groups. However, per-protocol and consumption-based analyses raised the possibility that prevention may be dose-dependent.
Early total enteral feeding in stable preterm infants a systematic review and...dineshdharel13
In conclusion, it seems feasible and safe to start total enteral feeding in stable VLBW infants born with birth weight greater than 1000–1200g. This approach can reduce the need of intravenous fluid or PN and its adverse consequences as well as decrease the length of hospital stay for these infants. A larger randomized trial is needed to ensure ETEF is not associated with increased risk of NEC in stable preterm infants with birth weight greater than 1000g and gestational age greater than 28 weeks. Furthermore, there is a need to explore whether ETEF regimen is feasible in extremely low birth weight infants.
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is an open access international journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
4th july 2020 daily global regional and local rice e newsletterRiceplus Magazine
Scientists from ICRISAT and collaborators have uncovered a molecular mechanism controlling male fertility in pigeonpea crops. They found that temperature affects whether plants are male fertile or sterile - below 24°C they are fertile, above they are sterile. Applying plant hormones can also reverse sterility at some temperatures. This finding could enable developing improved hybrid pigeonpea varieties using cheaper two-line hybrid technology instead of three-line technology. The researchers also forecast a record global cereal production in 2020, with the stock-to-use ratio reaching a twenty-year high.
Fibrinogen concentration and thrombin levels in pregnant women in nnewi, anam...Alexander Decker
This study examined fibrinogen concentration and thrombin time (TT) levels in 195 pregnant women in Nigeria compared to 150 non-pregnant women. Fibrinogen concentration and TT were significantly higher in pregnant women compared to non-pregnant women. Fibrinogen concentration and TT levels increased with each trimester of pregnancy and were highest in the third trimester. The increases in coagulation factors during pregnancy are likely due to hormonal changes and inflammation of pregnancy to prepare the body for potential blood loss during childbirth. Baseline measurements of these coagulation factors during antenatal visits could help detect any abnormalities.
This study aimed to evaluate the reproducibility and validity of a food frequency questionnaire (FFQ) to assess intake of polyphenol-rich foods in pregnant women in Brazil. 120 pregnant women participated in two interviews where they completed the FFQ and 24-hour dietary recalls. 93 women also completed 3-day food diaries and provided urine samples. The FFQ showed moderate to high correlations with the 24-hour recalls and food diaries. The correlation between the FFQ and urinary polyphenol levels was low but significant. The study concluded that the FFQ is reproducible and valid for quantifying intake of total polyphenols in pregnant women.
This study validated a food frequency questionnaire (FFQ) used to measure fruit, vegetable, and tea intake in pregnant women in Norway. The FFQ estimates were compared to biomarkers (urinary flavonoids and plasma carotenoids) and a 4-day weighed food diary. Correlations between the FFQ and biomarkers provided evidence that the FFQ could reliably estimate intake of certain foods, with validity coefficients of 0.65 for citrus fruit/juice and 0.59 for cooked vegetables. Overall, the validation study demonstrated the FFQ's ability to estimate fruit, juice, vegetable and tea intake in pregnant Norwegian women.
Effect of polyphenols on the intestinal and placental 2012gisa_legal
This document summarizes a research article that studied the effect of polyphenols on the intestinal and placental transport of some bioactive compounds. Some key findings of the research article include:
1) Different classes of polyphenols can affect the transport of organic cations, glucose, thiamine, and folic acid at the intestinal and placental barriers.
2) Within the same phenolic family, different compounds may have opposite effects on the transport of certain molecules.
3) Acute and chronic exposures to polyphenols do not always produce the same results, so care is needed when extrapolating findings.
4) The combined effect of polyphenols may differ from the individual effects
This study examined the effects of restricting polyphenol-rich foods in the diets of pregnant women in their third trimester on fetal ductal flow dynamics. 46 pregnant women consuming high levels of polyphenols were asked to restrict these foods for 2 weeks or more. Their fetuses showed significant decreases in ductal blood flow velocities and right ventricular size, as well as an increase in ductal pulsatility index. A control group of 26 women showed no significant changes. The study suggests that restricting maternal polyphenol intake in the third trimester can improve fetal ductal flow and right heart dimensions in normal pregnancies, as seen previously in cases of ductal constriction.
1) Twelve fetal lambs were studied before and after their mothers were given either green tea or water for one week. 2) Echocardiography after one week showed signs of ductal constriction in all lambs whose mothers drank green tea, including increased ductal velocities and right ventricular enlargement. 3) Autopsies also showed enlarged and thickened right ventricles in lambs exposed to green tea compared to controls. Histology found the ductal medial avascular zone was significantly thicker in green tea lambs versus controls, indicating ductal constriction.
O documento lista alimentos ricos em polifenóis como uvas, erva-mate, chás, chocolate preto, frutas cítricas e hortaliças. Estudos mostram que o consumo desses alimentos na gravidez pode afetar o fluxo do ducto arterial fetal. Um questionário de frequência alimentar foi desenvolvido para avaliar o consumo de alimentos ricos em polifenóis por grávidas.
The document discusses fetal ductus arteriosus and factors that influence its closure after birth. It notes that during fetal life, the ductus arteriosus shunts most blood from the pulmonary artery to the aorta. After birth, closure is initiated by increased oxygen levels and mediated by prostaglandins and endothelins. The ductus possesses smooth muscle that is influenced by relaxing factors like prostaglandins and constricting factors like oxygen. Drugs that inhibit prostaglandin synthesis like indomethacin can cause premature ductal constriction. The document also discusses how a maternal diet high in polyphenols from foods like tea, grapes, oranges, and chocolate may interfere with fetal ductal
This study examined the effects of maternal consumption of polyphenol-rich foods during late pregnancy on fetal ductus arteriosus blood flow dynamics. Doppler ultrasound was used to compare ductal blood flow velocities and right-to-left ventricular dimensions in 102 fetuses exposed to high maternal polyphenol intake versus 41 unexposed fetuses. Exposed fetuses had higher ductal velocities and right-to-left ventricular ratios, indicating potential inhibition of prostaglandin synthesis from polyphenols and effects on ductal constriction. The findings suggest maternal polyphenol-rich food intake during late pregnancy may impact fetal ductal dynamics and warrant changes to perinatal dietary guidance.
This document provides documentation for the USDA Database for Flavonoid Content of Selected Foods, Release 2.1. It summarizes the database contents and describes the methodology used to compile flavonoid values from various sources and standardize the data. Key points include:
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- Values come from the USDA's own analyses as well as published studies meeting quality criteria. Data sources include articles from 2002-2005 and a USDA survey of fruits/vegetables.
- Values are reported based on fresh weight and standardized procedures to
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2) São apresentados os padrões hemodinâmicos em cardiopatias congênitas e como eles se refletem no eletrocardiograma.
3) Os principais elementos do eletrocardiograma no recém-nascido são descritos, incluindo a análise sistemática do traçado normal e alterações sugestivas de cardiop
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Realizacao e interpretacao do ecg no pre hospitalargisa_legal
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2) Three-dimensional and four-dimensional imaging using techniques like STIC can accurately diagnose congenital heart disease at specialized centers, though the added value over 2D imaging alone is limited.
3) Fetal echocardiography allows identification of congenital heart disease before birth, improving parental preparation and newborn stability by guiding antenatal and postnatal management.
The document discusses the continued importance and value of the electrocardiogram (ECG) for cardiologists. It summarizes several ways that analyzing the ECG can help identify patients at high risk for sudden cardiac death, diagnose cardiac conditions, and predict outcomes. For example, it describes how a prolonged QTc interval on the ECG is a risk factor for sudden cardiac death and how the presence and degree of left ventricular hypertrophy shown on an ECG can predict future heart failure and cardiovascular events. The document advocates that clinicians should continue utilizing the ECG as it provides vital diagnostic information to guide patient care and treatment decisions.
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1. O documento apresenta diretrizes para interpretação do eletrocardiograma de repouso da Sociedade Brasileira de Cardiologia.
2. Discutem a importância do eletrocardiograma como ferramenta diagnóstica e sua utilização na prática clínica para avaliar doenças cardíacas.
3. Fornecem critérios eletrocardiográficos para caracterização de diferentes tipos de arritmias cardíacas como ritmo sinusal, taquicardia sinusal, extrasístoles atriais
O documento relata o caso de uma criança de 6 anos com isomerismo atrial esquerdo que apresentou disfunção do nó sinusal com pausas sinusais de até 2,4 segundos durante monitoramento cardíaco de 24 horas. Um marcapasso definitivo foi implantado com sucesso para tratar a disfunção sinusal.
Surfactante tratamiento prevencion y tratamientoMauricio Piñeros
The document summarizes clinical trials comparing animal-derived surfactants for treating neonatal respiratory distress syndrome. It finds:
1) Calfactant provides short-term benefits like faster weaning from ventilation compared to beractant, likely due to its higher surfactant protein B content, though it does not reduce mortality or oxygen need at 36 weeks.
2) Studies found no clear advantage of alveofact over beractant, as alveofact's higher surfactant protein B is balanced by beractant's higher phospholipid dose.
3) Poractant may have advantages over beractant for some secondary outcomes when a higher initial dose is used, strengthening the case for poract
This randomized clinical trial compared two treatment regimens of natural surfactant preparations, Curosurf and Survanta, in 75 neonates with respiratory distress syndrome (RDS). Infants receiving Curosurf had a more rapid improvement in oxygenation and required lower ventilatory support up to 24 hours after treatment compared to those receiving Survanta. Complication rates including pneumothorax and severe intracranial hemorrhage were lower in the Curosurf group, though differences were not statistically significant. The Curosurf treatment regimen resulted in faster clinical improvement for RDS.
A randomised, double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in
the prevention of necrotising enterocolitis (NEC) in newborns weighing <1500 g.
This document discusses the use of probiotics in the neonatal intensive care unit (NICU) to help prevent diseases like necrotizing enterocolitis (NEC). It provides background on the development of the infant gut microbiome and how probiotics may benefit preterm infants by competing with pathogens, producing antimicrobial substances, and modulating the immune system. Several studies cited found probiotic supplementation significantly reduced the risk of NEC and mortality in very low birth weight infants. Meta-analyses support the routine use of probiotics in the NICU.
This document reviews the evidence from clinical trials comparing different surfactant preparations used to treat respiratory distress syndrome (RDS) in preterm infants. It discusses the benefits of natural surfactants over synthetic surfactants, noting that natural surfactants contain surfactant proteins SP-B and SP-C which enhance their function. It also summarizes four key clinical trials that directly compared the efficacy of different natural surfactant preparations (Curosurf, Survanta, Infasurf, Alveofact), noting they used different doses and treatment protocols. The document concludes that while natural surfactants are generally preferred to older synthetic preparations, results of trials comparing newer synthetic surfactants to natural surfactants are
Food allergy has been long recognized and well documented. Other adverse reactions to foods first referred to as “toxic idiopathies” by John Freeman, co inventor of immunotherapy, at the early part of the 1900s can be mediated by and have their impact on the nervous and endocrine systems. It can also be mediated by pharmacologic mechanisms and can also affect any part of the body. There’s a great clinical need to accurately identify triggers of adverse reactivity as they have now been linked with even the most serious of modern maladies and diseases. In fact, inflammation is the hallmark of metabolic syndrome. Given the multitude of pathogenic mechanisms underlying adverse reactions to foods and other environmental exposures it is necessary that a utilizable and cost effective technology be understood so that its application be utilized under the appropriate circumstances.
KEY LEARNING POINTS
• The natural ability of certain foods to initiate an inflammatory response and induce metabolic disruptions and counterbalancing mechanisms to prevent that
• How foods can trigger “danger signals” for the immune system
Pharmacologic vs. immunologic reactions to foods
• Is there a common final pathway of all these mechanisms that can reliably indicate triggers of clinical pathology?
• Cellular testing vs. serologic testing: The advantages of cellular testing
Introduction: Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy. Methods: Rats were treated twice daily with pantoprazole sodium (PTZ; 10 mg/kg peroral) or vehicle for a total of 10 days. In some experiments, Diclofenac sodium (DCF; 9 mg/kg) or vehicle was administered orally twice daily for the final 5 days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12 hours after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated. Results: The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ. Conclusions: This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit, serum albumin, serum total protein levels and IP alteration, known to occur in patients receiving NSAIDs. Additionally, this paper provides yet another evidence for PPI induced exacerbation of NSAID enteropathy.
This study compared the efficacy of two surfactant treatments, poractant alfa and beractant, in very premature infants with respiratory distress syndrome. Fifty-two infants between 24 and 29 weeks gestation were randomly assigned to receive either poractant alfa or beractant. The study found that infants receiving poractant alfa required lower respiratory support as measured by mean airway pressure and respiratory index over the first 72 hours of life. Additionally, more infants in the poractant alfa group were extubated by 48 and 72 hours compared to the beractant group. While the study was not powered to detect differences in morbidities, rates of bronchopulmonary dysplasia and death were
This randomized controlled trial compared the efficacy of poractant alfa and beractant in treating 52 very premature infants with respiratory distress syndrome (RDS). Infants treated with poractant alfa required lower mean airway pressure and respiratory index to maintain oxygenation compared to beractant-treated infants over the first 72 hours of life. More infants in the poractant alfa group were extubated at 48 and 72 hours compared to the beractant group. While the study was not powered to detect differences in morbidities, rates of bronchopulmonary dysplasia and death were similar between the two groups.
This study compared the efficacy of two animal-derived surfactants, poractant alfa and beractant, in treating respiratory distress syndrome (RDS) in preterm infants. The study found that infants treated with poractant alfa required significantly less oxygen in the first 5 days after treatment compared to those treated with beractant. Infants in the poractant alfa group also had higher rates of extubation within 3 days. Additionally, poractant alfa treatment resulted in fewer infants requiring multiple doses of surfactant compared to beractant treatment. While mortality and other outcomes were similar between groups, survival without bronchopulmonary dysplasia at the end of the study period was significantly higher
This study examined the pharmacokinetics of porcine surfactant in 61 preterm infants with respiratory distress syndrome (RDS) who received doses of either 100 mg/kg or 200 mg/kg. Tracheal aspirates were collected from infants over time and analyzed for the presence of a stable isotope label added to the surfactant. Higher and longer-lasting levels of the surfactant marker were found in infants receiving 200 mg/kg compared to 100 mg/kg, along with fewer needing repeat doses and better oxygenation. The results suggest that a 200 mg/kg dose of porcine surfactant may be more effective for treating RDS in preterm infants.
The document summarizes a study that compared outcomes for 150 premature infants treated with two different natural surfactants: poractant alfa (Curosurf) and beractant (Survanta). The study found that infants treated with poractant alfa had a significantly shorter duration of intubation but no significant differences in other outcomes like mortality, morbidity, duration of oxygen therapy or hospitalization between the two groups. While poractant alfa appeared superior in reducing intubation time, the study concluded there was no clear overall superiority of one surfactant over the other.
This document summarizes several studies on factors related to bronchopulmonary dysplasia (BPD) in preterm infants. One study found that maternal smoking during pregnancy doubled the odds of BPD in infants, and was also associated with prolonged ventilation and late respiratory disease. Another study found that endothelial cell dysfunction in umbilical vein cells was associated with BPD or death in extremely preterm infants. A third study found that infants treated with caffeine in the neonatal period had better lung function at 11 years of age compared to placebo, mediated by caffeine's ability to reduce rates of BPD.
Fetal exposure to bisphenol a as risk factor for the childhood asthmaricguer
This study investigated the effects of perinatal bisphenol A (BPA) exposure on the development of allergic asthma using a mouse model. The researchers found that prenatal BPA exposure, but not solely postnatal exposure from breast milk, enhanced susceptibility to developing asthma-like symptoms in response to allergen sensitization. Gene expression analysis revealed delayed expression of the BPA-metabolizing enzyme Ugt2b1 in mouse fetuses and newborns, which may explain their enhanced susceptibility to the estrogenic effects of BPA crossing the placenta. The critical window of enhanced susceptibility was found to be prenatal exposure.
Final Oocyte Maturation: HCG VS GNRH Agonist by Dr. Abayomi Ajayiabayomi ajayi
This document discusses methods for final oocyte maturation in IVF treatment. It notes that human chorionic gonadotropin (HCG) has traditionally been used but gonadotropin-releasing hormone (GnRH) agonists can also be used to reduce the risk of ovarian hyperstimulation syndrome (OHSS). While GnRH agonists prevent OHSS, they are associated with lower pregnancy rates. However, combining a GnRH agonist trigger with low-dose HCG or vitrification of all embryos may optimize pregnancy rates while still preventing OHSS. The optimal luteal phase support when using a GnRH agonist trigger remains an area of ongoing research.
Recovery from developmental nonylphenol exposure is possible i. maleAlexander Decker
This study examined whether the effects of developmental exposure to the endocrine disrupting chemical nonylphenol (NP) could be reversed in subsequent unexposed generations of rats. Female rats were exposed to NP during pregnancy and lactation, and their offspring (F1 generation) showed increased body weight and hyperadrenalism at adulthood. The F1 females were bred to produce the F2 generation without further NP exposure. The F2 offspring did not show increased body weight or hyperadrenalism, indicating the developmental effects of NP exposure were reversed. This suggests that the "default state" can be recovered after a generation that experiences the health impacts and costs of developmental NP exposure.
Beneficial Effects of Curcumin Inmaternal and Fetal Oxidativestress and Brain...Prof. Hesham N. Mustafa
This study investigated the protective effects of curcumin against lead-induced oxidative stress and brain damage in pregnant rats and their fetuses. Pregnant rats were exposed to two doses of lead acetate, with or without curcumin supplementation. Lead exposure resulted in toxicity for both mothers and fetuses, as well as increased oxidative stress and brain histopathology. Co-treatment with curcumin significantly reduced lead levels and oxidative stress, and improved brain histopathology. The results suggest that curcumin has an ameliorative effect against lead-induced neurotoxicity by reducing oxidative stress and reversing tissue damage.
Bifidobacterium strain that helps reduce body fatBiopolis_SL
Bifidobacterium animalis subsp. lactis strain CECT 8145 is able to reduce body fat content and improve metabolic syndrome biomarkers. Here, we report the draft genome sequence of this strain, which may provide insights into its safety status and functional role.
This document discusses Gastro Esophageal Reflux Disease (GERD) in infants. It provides definitions of key terms like GER and GERD. It reviews the epidemiology and natural history of GER in infants, noting that the prevalence of daily regurgitation peaks between 1-6 months of age in around 70% of infants. It discusses the anatomy and physiology involved in GER and reviews approaches to diagnosing GERD in infants, including history, physical exam, upper GI imaging, endoscopy, and pH monitoring. Non-pharmacological and pharmacological treatment options are also covered.
Similar to Experim toxicol pathology (mecanismo) (20)
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1. Elsevier Editorial System(tm) for Experimental and Toxicologic Pathology
Manuscript Draft
Manuscript Number:
Title: Inflammation and oxidative stress are involved in the polyphenol-induced ductus arteriosus
constriction in pregnant sheep
Article Type: Full Length Article
Keywords: polyphenols; ductus arteriosus; pregnancy; fetal echocardiography; oxidative stress;
inflammation; sheep
Corresponding Author: Prof. Solange Cristina Garcia,
Corresponding Author's Institution: Federal University of Rio Grande do Sul
First Author: Guilherme B Bubols
Order of Authors: Guilherme B Bubols; Paulo Zielinsky; Antonio L Piccoli Jr; Luis H Nicoloso; Izabele
Vian; Angela M Moro; Mariele F Charão; Natália Brucker; Rachel P Bulcão; Sabrina N Nascimento;
Marília Baierle; Marcelo M Alievi; Rafael N Moresco; Melissa Markoski; Solange Cristina Garcia
3. COVER LETTER
Dear Editor,
I present the manuscript entitled “Inflammation and oxidative stress are
involved in the polyphenol-induced ductus arteriosus constriction in pregnant
sheep” for evaluation in Experimental and Toxicologic Pathology, because I
consider this Journal very important in the area of Cardiovascular Pathology
and Toxicology aspects.
Moreover, the authors confirm that this article has not been published
previously in any journal and it is not under consideration for publication
elsewhere. If this article is accepted, it will not be published elsewhere, in
English or any other language. All authors approved this publication, being
responsible for its content.
The authors confirm also that there is no conflict of interest.
The correspondence Author:
Prof Dr Solange Cristina Garcia
E-mail address: solange.garcia@ufrgs.br (S. C. Garcia).
Address: Avenida Ipiranga 2752, Santa Cecília, Porto Alegre, RS, Brazil.
CEP.:90610-000.
Tel. (+55) 3308-5297. Fax (+55) 51 3308-5437
*Cover Letter
4. Inflammation and oxidative stress are involved in the polyphenol-induced
ductus arteriosus constriction in pregnant sheep
Guilherme B. Bubolsa,b, Paulo Zielinskyc, Antônio L. Piccoli Jrc, Luiz H.
Nicolosoc, Izabele Vianc, Angela M. Moroa,b, Mariele F. Charãoa,b, Natália
Bruckera,b, Rachel P. Bulcãoa,b, Sabrina N. Nascimentoa,b, Marília Baierlea,b,
Marcelo M. Alievid, Rafael N. Morescoe, Melissa Markoskic, Solange C.
Garciaa,b.
a Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade
Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
b Laboratório de Toxicologia (LATOX), Departamento de Análises Clínicas,
Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
c Instituto de Cardiologia do Rio Grande do Sul/FUC (IC/FUC), Porto Alegre,
RS, Brazil.
d Hospital de Ciências Veterinárias (HCV), Universidade Federal do Rio Grande
do Sul (UFRGS), Porto Alegre, RS, Brazil.
e Laboratório de Bioquímica Clínica, Universidade Federal de Santa Maria
(UFSM), Santa Maria, RS, Brazil.
* Direct correspondence to Prof Dr Solange Cristina Garcia. E-mail address:
solange.garcia@ufrgs.br (S. C. Garcia). Address: Avenida Ipiranga 2752, Santa
Cecília, Porto Alegre, RS, Brazil. CEP: 90610-000 Tel.: (+55) 3308-5297. Fax:
(+55) 51 3308-5437
*Manuscript
5. Abstract
Despite the promising antioxidant and anti-inflammatory effects of polyphenols,
we have recently reported that maternal consumption of polyphenol-rich foods
(PRF) interferes with ductus arteriosus (DA) flow in sheep and human fetuses’
hearts, probably by an anti-inflammatory effect, and also shown that restriction
of human PRF ingestion reverses ductal constriction. In this work, an
experimental study was carried out with pregnant sheep after oral PRF
supplementation for 14 days. Fetal echocardiography, analysis of oxidative
stress and inflammatory biomarkers and total polyphenol (TP) urinary excretion
were performed. We report that high polyphenol intake induced DA constriction
(71.6% increase in systolic and 57.8% in diastolic velocities and 18.9%
decrease in pulsatility index), accompanied by a 1.7-fold increase in TP
excretion, 2.3-fold decrease in inflammatory NOx and changes in redox status,
such as higher protein carbonyls (1.09 ± 0.09 and 1.49 ± 0.31), CAT (0.69 ±
0.39 and 1.44 ± 0.33) and GPx (37.23 ± 11.19 and 62.96 ± 15.03) despite the
lower lipid damage (17.22 ± 2.05 and 12.53 ± 2.11) and nonprotein thiols (0.11
± 0.04 and 0.04 ± 0.01) found before and after treatment, respectively. Ductal
parameters correlated to NOx, CAT, GPx and protein carbonyls. These results
highlight the importance to reduce maternal intake of PRF in late pregnancy in
light of the possible induction of fetal duct constriction through an anti-inflammatory
action of polyphenols and the involvement of oxidative stress.
Keywords: polyphenols; ductus arteriosus; pregnancy; fetal echocardiography;
oxidative stress; inflammation; sheep.
6. 1. Introduction
Polyphenols are plant secondary metabolites which are well studied for
contributing to the prevention of cancer, cardiovascular and neurodegenerative
diseases (Arroo et al., 2009, Benavente-Garcia and Castillo, 2008, Linseisen
and Rohrmann, 2008, Zamora-Ros et al., 2012). Polyphenolic compounds are
found in a variety of food sources, especially vegetables, fruits, herbs, green tea
(Camellia sinensis), cocoa and nuts. Most health benefits ascribed to
polyphenols seem to be due to their prominent antioxidant and anti-inflammatory
effects, considering that oxidative damage and inflammation are
usually present in chronic and degenerative diseases (Biesalski, 2007, Dasuri et
al., 2012, Zilka et al., 2012). Polyphenol consumption is mostly related to dietary
ingestion but supplementation is also common. Despite the scarce evidence
about the safety of polyphenol consumption, these compounds are normally
well tolerated in usual amounts, presenting few adverse effects that may either
be found when polyphenol-rich foods (PRF) are ingested at higher doses
(Bonkovsky, 2006, Ferry et al., 1996, Shoskes et al., 1999) or after interactions
with other drugs (Dahan and Altman, 2004, Marzolini et al., 2004).
During the course of pregnancy, a vascular duct called ductus arteriosus
(DA) is open or patent and plays an important role in the fetal heart dynamics in
order to allow the blood flow to circulate into lower fetal portions. The patency of
the DA is controlled by local production of prostaglandins and nitric oxide, and
as gestation proceeds, the duct becomes less sensitive to dilating
prostaglandins and more sensitive to constricting influences, e.g. arterial
oxygen tension (Archer, 1996). The DA closes physiologically after birth with the
onset of the pulmonary circulation (Bergwerff et al., 1999). However, the
7. premature DA constriction in the third trimester of pregnancy is normally
associated to pulmonary hypertension in the newborn or even fetal death.
Premature DA constriction has been reported after administration of non-steroid
anti-inflammatory drugs (NSAID) or glucocorticoids (Moise, 1993), thus
administration of these drugs is usually avoided in late-pregnancy or the fetuses
should be assessed by echocardiographical analysis.
Evidences indicate that maternal consumption of prostaglandin
synthetase inhibitors leads to DA sensibilization, which may cause its
constriction (Archer, 1996). Our group has previously reported that maternal
consumption of PRF interferes with ductal flow in human fetuses, probably by a
polyphenol-induced anti-inflammatory effect (Zielinsky et al., 2010), and also
that restriction of PRF consumption was able to reverse ductal constriction
(Zielinsky et al., 2012b). In this context, the present study aimed to investigate
the interrelations of fetal duct dynamics, oxidative damage and inflammation
after PRF administration to pregnant sheep in late pregnancy.
2. Materials and methods
2.1. Experimental study
The study included six adult female Corriedale sheep (90-100kg) in late
pregnancy (gestational age >120 days), which corresponds to the third trimester
of pregnancy, were fed for 2 weeks with standardized amount of PRF (basal
intake+3100 mg/day). The ewes received the usual diets, which consisted of
alfafa, milled corn and mineral salt which was supplemented with polyphenol-rich
foods selected by nutritionist (dried tomatoes, dried apples, milled and dried
green tea leaves and raw soy grains) and the total polyphenol levels in the food
8. were quantified by the spectrophotometric Folin-Ciocalteu reaction. Before the
14-day period, the animals were adapted for 7 days in the experimentation site.
Animals were kept and handled in a proper location in the University Veterinary
Hospital (HCV/UFRGS) and water was available ad libitum for consumption
according to the guidelines of the local committee. This study was approved by
the Ethics Committee in Research (IC/FUC) under Nr. UP3888/06.
2.2. Collection of biological samples
Samples before treatment (BT) or basals as well as samples after
treatment (AT) were collected before and after the 14 days of experiment,
respectively. At both moments, venous blood samples were collected by
venipuncture into Vacutainer® (BD Diagnostics, Plymouth, UK) tubes with
EDTA, sodium heparin and without anticoagulants. Furthermore, urine samples
were collected in both moments of the study in sterile and light-protected
recipients, and stored at -80°C until analysis. The blood and urine collection
procedures were performed by experienced veterinaries.
2.3. Fetal Doppler echocardiography
Echocardiograms were obtained using two-dimensional Doppler color
flow imaging with convex transducers 7 or 5 MHz and/or a sectorial phased
array of 3.5 or 5 MHz with the General Electric Logic 4 system, with 2D pulsed
and continuous Doppler and color flow mapping capability. At 2D
echocardiography, the ductus arteriosus was imaged in sagittal or longitudinal
planes and Doppler velocities were measured by positioning the sample volume
in the descending aortic end of the ductus arteriosus, with a maximal insonation
9. angle of 20º. The ratio between right and left ventricular dimensions was
obtained on a four-chamber view in late diastole to assess right ventricular
repercussion. An increase in mean ductal velocities and a decrease in mean
pulsatility index greater than 20% after exposure were considered signs of
ductal constriction, as previously established in sheep by our group (Zielinsky et
al., 2012a). All examinations were performed by the same pediatric
cardiologists with experience in fetal echocardiography. The presence of ductal
flow turbulence, tricuspid and/or pulmonary regurgitation and leftward
interventricular septal bulging were searched. Pulsatility index was calculated
by (systolic peak velocity - diastolic peak velocity/ mean velocity).
2.4. Laboratorial analyses
2.4.1. Total polyphenol urinary excretion
Quantification of total polyphenols (TP) in urine was performed as
previously reported (Medina-Remon et al., 2009). Briefly, urine samples stored
at -80ºC were thawed for 3 h on ice bath and centrifuged at 4ºC for 10 min.
Samples were diluted, acidified and then a cleanup procedure by solid phase
extraction with Waters Oasis ® MAX 30-mg cartridges (Milford, MA, USA) was
performed. Extracted eluates were added to 96-well microplates for the reaction
with the Folin-Ciocalteu reagent 2M and 20% sodium carbonate and incubated
for one hour in the dark. Absorbances were read at 765 nm. Urinary creatinine
was determined in order to correct TP excretion by spectrophotometry using
commercial kits (Doles reagents, Goiânia, GO, Brazil). Results were expressed
as mg gallic acid equivalents (GAE) g-1 creatinine.
10. 2.4.2. Lipid peroxidation
Lipid peroxidation was evaluated by the measurement of thiobarbituric
acid reactive substances (TBARS), in which plasma-EDTA samples were
processed and absorbance was measured at 535 nm as previously described
(Ohkawa et al., 1979). TBARS levels were estimated as μmol malondialdehyde
(MDA) equivalents L-1 using tetramethoxypropane as a standard.
2.4.3. 3-Nitrotyrosine (3-NT) levels
3-Nitrotyrosine levels were assessed in plasma by a noncompetitive
ELISA method (Weber et al., 2012). Total proteins were measured by the
Bradford method and plasma was diluted to 2 mg protein mL-1 and incubated in
Maxisorb multiwallplates (Nunc Immuno 96 Microwell™ Maxisorp) overnight at
4ºC in the dark. Polyclonal anti-nitrotyrosine (Millipore) and monoclonal goat
anti-rabbit IgG, HRP-conjugate (Millipore) were used as primary and secondary
antibodies, respectively. After color development, the reaction was stopped and
the absorbance was measured at 492 nm in triplicates and results were
expressed as ρmol mg-1 protein.
2.4.4. Protein carbonyl (PCO) levels
Protein carbonyls were determined by a described noncompetitive ELISA
method following some modifications (Buss et al., 1997). Total protein levels in
plasma were measured by the Bradford method. Plasma was diluted with PBS
buffer (4 mg protein mL-1) and then derivatized with 2,4-dinitro-phenylhydrazine
(DNPH) and incubated in Maxisorb multiwallplates (Nunc Immuno 96
Microwell™ Maxisorp) overnight at 4ºC in the dark. Protein carbonyls were
11. detected using a dinitrophenyl rabbit IgG-antiserum (Sigma, Deisenhofen,
Germany) as the primary antibody and a monoclonal anti-rabbit immunoglobulin
G peroxidase conjugate (Sigma) as the secondary antibody. Color was
developed with o-phenylenediamine and H2O2 addition and the reaction was
stopped with H2SO4 after 15 min incubation at 37ºC. Absorbances were
measured at 492 nm in triplicates and results were expressed as nmol mg-1
protein.
2.4.5. Reduced nonprotein thiol groups
Determination of reduced nonprotein thiol groups in erythrocytes was
performed by a spectrophotometric method (Ellman, 1959). Red blood cells
(RBC) samples were hemolyzed by Triton X-100, and after 10 min were
precipitated with 20% trichloroacetic acid (w/v). After centrifugation, 10 mM 5,5′-
dithio-bis(2-nitrobenzoic acid) (DTNB) was added to the supernatant aliquots.
DTNB, also known as Ellman's reagent, reacts with reduced thiols to produce a
mixed disulfide (Ellman's derivate) and the anion 5-thio-2-nitrobenzoate (TNB),
which is quantified by its strong visible absorbance at 412 nm as an indirect
measure of reduced thiols. Reduced non protein thiol levels were expressed as
μmol mL-1 RBC.
2.4.6. Enzymatic antioxidants
Catalase (CAT) activity was determined by a previously described
method based on the decomposition of hydrogen peroxide (H2O2) by catalase
(Aebi, 1984). Enzymatic activity was evaluated by monitoring the rate of
decrease in H2O2 absorbance at 240 nm during 5 min with readings every 20s
12. at 37ºC. CAT activity was expressed as K CAT mg-1 protein. For the
determination of the enzymatic activity of glutathione peroxidase (GPx), a
method was adopted in which absorbances were monitored at 340 nm during 6
min with readings every 20s at 37ºC (Paglia and Valentine, 1967). GPx activity
was expressed as μmol NADPH min-1 mg-1 protein. Furthermore, glutathione S-transferase
(GST) activity was determined at 340 nm using 1-chloro-2.4-
dinitrobenzene (CDNB) as substrate and 0.15 M glutathione (GSH) (Habig et
al., 1974). GST activity was expressed as nmol CDNB conjugated with GSH
min-1 mg-1 protein.
2.4.7. Prostaglandin E2 (PGE2) levels
PGE2 levels were measured by commercial kit based on a competitive
EIA method (Enzo Life Sciences, Farmingdale, NY, USA), following the
manufacturer’s instructions. Absorbance was determined at 405 nm and results
were expressed as ρg mL-1.
2.4.8. Nitrite/nitrates (NOx) ratio
Nitrites/nitrates levels were determined in serum according to the
modified Griess method (Tatsch et al., 2011). First, nitrates present in samples
were reduced to nitrites after reaction with vanadium (III) chloride (VCl3) 0.08%.
Then a mixture of sulphanilamide 2%, N-(1-naphthyl)ethylenediamine (NED)
0.2% and orthophosphoric acid in distillated/deionized water (Griess reagent)
was added to the samples. Sulfanilamide reacts with nitrites in the samples to
form a diazonium salt that reacts with NED to produce a purple-azo-dye
13. product, which is measured at 540 nm in Cobas Mira® (Roche Diagnostics,
Basel, Switzerland). Results were expressed as μmol L-1.
2.5. Statistical analysis
Data were analyzed utilizing IBM SPSS Statistics software (version 19.0)
and all study variables were tested for normality by the Shapiro-Wilk test.
Comparisons between groups were performed by the Student’s t-test, for
variables with normal distribution, and the Mann-Whitney test for variables with
non normal distribution. Results are expressed as mean ± standard error of the
mean (SEM) or median (interquartile range), according to the distribution of
variables. Correlation tests used were Pearson’s correlation coefficient and
Spearman’s rank, for normal and non normal variables, respectively. Significant
differences were considered when p≤0.05.
3. Results
In order to investigate the flow dynamics in the fetal ductus arteriosus,
fetal hearts were analyzed by Doppler echocardiography. Analysis of
echocardiographical parameters showed a significant increase in systolic and
diastolic velocities (Figure 1A), as well as a decrease in pulsatility index (Figure
1B) in the animals after 14 days of dietary intervention when compared to the
basal state. Percentual differences between BT and AT, respectively, were
71.6% for SV (0.75 and 1.28 m s-1), 57.8% for DV (0.18 and 0.29 m s-1) and
18.9% for PI (2.49 and 2.02). Besides, echocardiographical images indicated a
constriction of the ductus arteriosus in the PRF-treated animals (Figure 1D) in
14. comparison to basals (Figure 1C), compatible with the previous parameters that
showed signs of ductal constriction.
Total polyphenol levels excreted in urine from the pregnant sheep after
PRF intake were significantly increased in the 14-day treated group compared
to basal (Figure 2).
As depicted in Table 1, the oxidative biomarkers were determined in
blood samples from the studied animals. Oxidative damages were evaluated by
biomarkers of lipid and protein damages. Lipid peroxidation as estimated by
TBARS levels showed a reduction after 14 days of study compared to the basal
state. Protein damage was investigated by the determination of protein carbonyl
(PCO) and 3-nitrotyrosine (3-NT) levels. Our results indicated that PCO was
significantly increased in the animals after 14 days of treatment and no
significant difference was found in 3-NT levels (p>0.05).
In addition, erythrocyte levels of reduced nonprotein thiols were
decreased in the treated group, comparing basal to 14 days (Table 1).
Considering the enzymatic antioxidant systems, the activities of glutathione
peroxidase (GPx) and catalase (CAT) were significantly increased after 14-day
treatments, while no significant changes were observed in glutathione S-transferase
(GST) activity.
Inflammatory biomarkers were investigated in serum from the studied
animals. Polyphenol treatment in sheep at the third trimester of pregnancy was
found to induce a decrease in NOx ratio after 14 days in comparison to the
basal state (Figure 3). Serum prostaglandin E2 (PGE2) was also determined
and no significant difference was found before and after 14-day treatment in
pregnant animals (data not shown).
15. Figure 4 shows negative correlations between NOx levels and GPx
activity (r=-0.755, p=0.004) and also between NOx levels and catalase activity
(r=-0.812, p=0.001). In addition, we have observed a positive correlation
between lipid peroxidation and NOx levels (r=0.748, p=0.005) and a negative
correlation between lipid peroxidation and the total polyphenol excretion (r=-
0.622, p=0.030 (Figure 5).
Ductal constriction parameters presented significant correlations between
each other. A positive correlation was found between SV and DV (r=0.686,
p=0.028) and a negative correlation between SV and IP (r=-0.712, p=0.021)
was observed. We also found that echocardiographical parameters were
associated to biomarkers of protein and lipid oxidative damage. Protein
carbonyls were correlated to SV (r=0.629, p=0.028), DV (r=0.905, p=0.0001)
and to IP (r=-0.772, p= 0.003). However, in relation to lipid peroxidation, we
found that TBARS presented inverse correlations to the echocardiographical
parameters, i.e. TBARS vs. SV (r=-0.746, p=0.013), TBARS vs. DV (r=-0.825,
p=0.003) and TBARS vs. IP (r=0.660, p=0.038). Antioxidant enzymes also
presented correlations with ductal parameters, for example CAT vs. SV
(r=0.672, p=0.033) and GPx vs. IP (r=-0.629, p= 0.05). In addition, significant
correlations between echocardiographical measures and inflammatory NOx
levels were also observed (Figure 6).
4. Discussion
In the present study, a high polyphenol intake in female sheep during late
pregnancy induced alterations in the ductal flow dynamics characteristic of fetal
duct constriction. Systolic and diastolic velocities were significantly increased
16. after the treatment with polyphenols in pregnant sheep compared to the basal
state (Figure 1A). A significant decrease in pulsatility index (Figure 1B) was also
found. A previous study from our group has demonstrated that green tea
extract, which also presents significant contents of polyphenols, when orally
administered to pregnant sheep was able to induce similar echocardiographical
alterations as observed in the present study (Zielinsky et al., 2012a), however
the underlying mechanisms responsible for the DA constriction were not
evaluated. In this scenario, this work aimed first to confirm that polyphenols
were effectively associated to the echocardiographical alterations and then to
propose the possible mechanisms involved in this process considering the most
frequently reported effects of polyphenolic compounds.
The increase in TP urinary excretion in pregnant sheep (Figure 2)
indicates that the oral administration of PRF was effective once polyphenols
were absorbed and eliminated in urine, representing an important biomarker of
total polyphenol intake. Once we could establish that the polyphenols ingested
were absorbed, the determination of biological effects and the possible
mechanisms of action of polyphenols become possible.
Subsequently, a mechanistic approach was performed by determining
oxidative stress and inflammatory biomarkers. Lipid peroxidation is usually
represented by the byproduct malondialdehyde and other aldehydes such as
hydroxynonenal, which are produced in the ROS-induced peroxidation of
membrane lipids and may be estimated as thiobarbituric acid reactive species
or TBARS. Our results indicated that polyphenol consumption was responsible
for a reduction in the lipid peroxidation found in sheep at the third trimester of
gestation. Polyphenols are markedly associated to antioxidant properties in
17. several studies (Biesalski, 2007, Bubols et al., 2012, Proteggente et al., 2002),
and the lower TBARS levels found in our study is in accordance to these
previous data. Lipid peroxidation during pregnancy has also been
demonstrated, especially with the approximation of labor, which is known for an
increasing ROS production (Mocatta et al., 2004).
Furthermore, in relation to oxidative damage, we have also shown that
protein carbonyls were increased in the treated animals (Table 1). Protein
damage was found despite the decrease in lipid damage, indicating the inability
of polyphenols to prevent oxidative damage through one signaling pathway, i.e.
protein damage rather than lipid damage. 3-Nitrotyrosine levels were not
significantly altered in the animals (p>0.05), which could be ascribed to the
short half-life of 3-NT in plasma described by other investigators as 1-2 hours
and the transient alterations in its levels is discussed as a consequence of
mechanisms such as protein degradation, repair or clearance (Greenacre and
Ischiropoulos, 2001, Ischiropoulos, 2009).
In this sense, it is expected that antioxidant defenses be naturally
mobilized as an attempt to prevent oxidative damages to biomolecules through
different mechanisms, such as enzymatic and non enzymatic antioxidants or
exogenous antioxidants (Berchieri-Ronchi et al., 2011, Poston et al., 2011). In
our study, the levels of reduced nonprotein thiols in sheep were decreased after
the experimentation period (Table 1). This finding suggests that despite the high
polyphenol consumption, the increase in the production of reactive species
typical of late pregnancy induced a mobilization of antioxidant defenses such as
nonprotein thiols in order to preserve tissues from oxidative damage.
18. Some alterations in the endogenous enzymatic antioxidants were
observed. Catalase and glutathione peroxidase enzymatic activities were
increased after the treatment (Table 1), confirming the previous results that
indicate the ROS overproduction in late pregnancy (Michelakis et al., 2004,
Mocatta et al., 2004, Reeve et al., 2001). Taken together, our results of GPx
enzymatic activity, TBARS and nonprotein thiols indicate the involvement of the
GPx and GSH system to scavenge the lipid peroxides generated in order to
avoid damage to lipid membranes.
We report that polyphenol consumption was able to induce a premature
constriction of the fetal duct as well as changes in the antioxidant status in
sheep. Polyphenols, which are well recognized exogenous antioxidants (Bubols
et al., 2012, Proteggente et al., 2002, Rice-Evans and Miller, 1996), possibly
acted synergistically with endogenous antioxidant defenses against ROS
unbalance, but were still associated to important echocardiographical
alterations in fetuses’ hearts. This dual behavior (protective and involved in DA
constriction) however is still to be fully understood. Considering that
polyphenols also present relevant anti-inflammatory activities (Marzocchella et
al., 2011, Middleton et al., 2000), the mechanism for ductal constriction may be
mostly due to the anti-inflammatory effect of polyphenols in comparison to their
antioxidant properties. In the present study, analysis of the oxidative damage
parameters indicated that protein damage was present in sheep during the third
trimester of pregnancy, in spite of the high polyphenol consumption, so the
overproduction of ROS in pregnancy could not be completely scavenged by the
endogenous antioxidant systems and some extent of oxidative stress could
19. have contributed to the premature cardiovascular alterations found in the
fetuses, in addition to the modulation of immune system.
Indeed, previous reports back up the involvement of ROS overproduction
in the induction of DA constriction through the activation of different signaling
pathways, such as by inhibiting voltage-gated potassium channels and
activating Rho-kinase signaling, which are associated to smooth muscle
contraction (Kajimoto et al., 2007, Michelakis et al., 2002, Thebaud et al., 2004)
and also affecting the mitochondrial redox state (Reeve et al., 2001).
Nitric oxide (NO) is a reactive nitrogen species (RNS) formed from the
action of the endothelial nitric oxide synthase (eNOS) that determines several
biological functions by acting as a signaling molecule, especially leading to
vasodilatation, neurotransmission and inflammation (Dusse et al., 2005). The
NO radical has a very short serum half-life and reacts with circulating reactive
species to produce different stable inorganic metabolites, such as nitrites and
nitrates (Romitelli et al., 2007), thus nitrite/nitrate (NOx) levels are often used as
a measure of NO production.
Lower NOx levels were found in the animals after higher polyphenol
ingestion (Figure 3). NO is a dilating substance to the vascular system which is
closely related to the immune system, and its lower levels in PRF-treated sheep
indicates that polyphenols were responsible for vascular constriction and an
anti-inflammatory effect. Moreover, studies have reported that during pregnancy
the dilating NO is responsible for maintaining the patency of the ductus
arteriosus, and that this influence is inverted in late pregnancy, as the fetal duct
becomes physiologically less sensitive to NO, which is responsible for the DA
constriction (Archer, 1996, Bergwerff et al., 1999). We have shown that
20. polyphenols are able to accelerate the physiological fetal duct constriction when
consumed in late pregnancy and thereby lead to a premature DA constriction.
Our results are in agreement with a clinical trial from Keller and co-workers
(2005), who demonstrated that premature newborns with patent ductus
arteriosus (PDA) presented an increased DA constriction after treatment with
both NOS inhibitor L-NMMA and indomethacin, showing the role of NO-mediated
anti-inflammatory effect in the induction of ductal constriction (Keller
et al., 2005).
In our study, no significant difference in PGE2 levels could be observed
in the animals. However, further biomarkers related to the prostaglandin
biosynthesis pathways should be evaluated, such as additional prostaglandins,
isoprostanes and arachidonic acid in serum or ciclooxigenases (COX) isoforms
in blood lymphocytes (Kallapur et al., 2011, Takahashi et al., 2000). In a recent
study, Chen and co-workers (2012) revealed the involvement of isoprostanes as
novel biomarkers associated to the oxidative stress and especially responsible
to promote a constriction of the ductus arteriosus in mice. The exposures to 8-
iso-PGF2α and 8-Iso-PGE2 isoprostanes were able to induce a fetal DA
constriction in preterm pregnant mice under fetal oxygen conditions through
binding thromboxane A2 (TxA2) receptors (Chen et al., 2012). Isoprostanes are
produced from the oxidative damage to membrane lipids, especially arachidonic
acid, while prostaglandins are released as a result of the enzymatic activity of
ciclooxigenases (Milne et al., 2007).
Polyphenol consumption in our study could have interfered mostly with
isoprostane synthesis compared to prostaglandins, indicating that COX-mediated
prostaglandin synthesis may not be entirely involved in the process,
21. as we reported by the absence of significant PGE2 alterations. The preference
for the isoprostane pathway is likely in the present study, considering the
concomitant involvement of oxidative stress and the anti-inflammatory action of
polyphenols, as previously demonstrated, and naturally deserves further
confirmatory studies.
The studies available on the ductus arteriosus dynamics have been
basically based on determining the influence of anti-inflammatory drugs
(NSAIDs or glucocorticoids) either in the induction of premature DA constriction
(Levy et al., 1999, Paladini et al., 2005, Rasanen and Jouppila, 1995) or in
cases of PDA, in which the pharmacological closure of the DA is searched
because the patency of the fetal duct is maintained after birth (Sivanandan et
al., 2013). Therefore, few studies have been conducted with a premature
constriction of the DA without any relation to NSAIDs intake (Kapadia et al.,
2010, Zielinsky et al., 2010, Zielinsky et al., 2012b), which is noteworthy since
these drugs are anti-inflammatory agents, while polyphenols in general present
anti-inflammatory and antioxidant activities leading to a situation in which
simultaneous effects are elicited, and as shown in our results.
Zielinsky and co-workers (2010) demonstrated that PRF intake during
late pregnancy was able to induce premature DA constriction in human fetuses
(Zielinsky et al., 2010) and recently reported the reversal of ductal constriction
after pregnant women were instructed not to consume foods with high
polyphenol contents (Zielinsky et al., 2012b). Similar observations have also
been detected in a case report described by Kapadia and co-workers (2010),
who associated the prenatal closure of the DA with the maternal ingestion of a
22. juice blend containing anthocyanins and proanthocyanidins (Kapadia et al.,
2010).
In addition to the increase in protein damage by protein carbonyl levels
(Table 1), we interestingly observed that oxidative modification to proteins was
associated to ductal alterations by the high correlations between PCO and SV,
PCO and DV and PCO and IP, indicating that the ductal constriction in pregnant
sheep was influenced by the involvement of protein damage, which may be
explained by the higher ROS production in late pregnancy. On the other hand,
lipid peroxidation was decreased in pregnant sheep after PRF intake (Table 1),
and echocardiographical parameters (SV, DV and IP) were inversely associated
to lipid damage, corroborating that lipid damage did not contribute to ductal
constriction and suggesting that polyphenols were able to promote some
protection against lipid damage thus diminishing TBARS.
Considering that polyphenols diminished lipid damage (Figure 5B) and
that polyphenols also led to a reduction of NOx levels (Figure 3A), it could be
explained that the PRF-treated animals, presenting diminished plasma NOx as
a result of polyphenols anti-inflammatory effect, would present less lipid
damage, as evidenced in Figure 5A, due to a polyphenol-induced antioxidant
effect and protection against lipid damage, once both activities were exerted by
polyphenols. Also, NO and its stable products nitrites and nitrates are reactive
nitrogen species (RNS) that could lead to lipid damage (O'Donnell et al., 1999),
so lower NOx levels could be responsible for the decreased lipid peroxidation.
Figure 6 presents negative correlations between both systolic and
diastolic velocities to NOx levels as well as the positive correlation between
pulsatility index and NOx. These findings corroborate the influence of the
23. decreased NOx levels in the development of fetal duct constriction in pregnant
sheep under high polyphenol consumption.
In addition to reactive nitrogen species (RNS), the increasing oxygen
tension that occurs in fetuses during late pregnancy near birth is responsible for
the physiological DA constriction (Archer, 1996, Michelakis et al., 2002) and
also increasing reactive oxygen species (ROS) have been reported in the
approximation of labor (Mocatta et al., 2004), corroborating our results of the
involvement of oxidative stress by the activation of the antioxidant enzymes
GPx and CAT in the third trimester of sheep gestation (Table 1), despite the
antioxidant effect found after high polyphenol consumption. The correlations of
SV versus CAT and IP versus GPx also confirm the involvement of antioxidant
enzymes in the premature ductal constriction. Regarding these endogenous
antioxidant enzymes, the antioxidant and anti-inflammatory behaviors of
polyphenols are observed in Figure 4, which shows that NOx was negatively
correlated to both GPx and CAT, showing that the increase in both endogenous
enzymatic antioxidants was associated to an anti-inflammatory activity after
polyphenol intake in sheep. Previous reports have shown that NO is able to
reversibly bind and inhibit catalase (Brown, 1995), explaining the high negative
correlation between both markers found in our study (Figure 4B).
To date, there is need for knowledge from animal models on all the
mechanisms involved in ductal constriction. The present study not only reports
that the consumption of high polyphenol levels during late pregnancy induces
constriction of the ductus arteriosus, but also indicates that the ability of
polyphenols to modulate the immune response is responsible for the
mechanism of ductal constriction induced by these compounds. Moreover, this
24. is to our knowledge the first work to confirm the involvement of anti-inflammatory
effect through NO downregulation as well as the modulation of
oxidative pathways in the premature induction of DA constriction in fetal lambs
after high polyphenol consumption from pregnant sheep. Although the
antioxidant mechanism was clearly involved after PRF intake and responsible
for benefits in the antioxidant status in the animals, the role of polyphenols’
antioxidant effect in the induction of fetal duct constriction seems to be
important in conjunction with the anti-inflammatory effect and worthy of future
investigations.
Finally, the present results stress the importance of dietary orientation to
decrease polyphenol consumption in late pregnancy to avoid premature DA
constriction and, importantly, provide evidence that the anti-inflammatory effect
of polyphenols was involved in sheep suffering from the ductal constriction
process as well as oxidative stress even after dietary polyphenol consumption.
Acknowledgments
This work was supported by Fapergs PPSUS Nr. 09/0023-0 grant to P.
Zielinsky. S.C. Garcia was granted CNPq/Universal (Nr. 479613/2009-5 and
484096/2011-7) and Fapergs (PqG-2010). G.B. Bubols is recipient of CAPES
Masters Degree fellowship; S.C. Garcia and P. Zielinsky are recipients of CNPq
Research Fellowships.
References
Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-6.
Archer N. Drug induced closure of patent ductus arteriosus. Heart.
1996;76:384-5.
25. Arroo RRJ, Androutsopoulos V, Beresford K, Ruparelia K, Surichan S, Wilsher
N, et al. Phytoestrogens as natural prodrugs in cancer prevention: dietary
flavonoids. Phytochem Rev. 2009;8:375-86.
Benavente-Garcia O, Castillo J. Update on uses and properties of citrus
flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory
activity. J Agric Food Chem. 2008;56:6185-205.
Berchieri-Ronchi CB, Kim SW, Zhao Y, Correa CR, Yeum KJ, Ferreira AL.
Oxidative stress status of highly prolific sows during gestation and lactation.
Animal. 2011;5:1774-9.
Bergwerff M, DeRuiter MC, Gittenberger-de Groot AC. Comparative anatomy
and ontogeny of the ductus arteriosus, a vascular outsider. Anat Embryol (Berl).
1999;200:559-71.
Biesalski HK. Polyphenols and inflammation: basic interactions. Curr Opin Clin
Nutr Metab Care. 2007;10:724-8.
Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese
green tea (Camellia sinensis). Ann Intern Med. 2006;144:68-71.
Brown GC. Reversible binding and inhibition of catalase by nitric oxide. Eur J
Biochem. 1995;232:188-91.
Bubols GB, Vianna DD, Medina-Remon A, von Poser G, Lamuela-Raventos
RM, Eifler-Lima VL, et al. The Antioxidant Activity of Coumarins and Flavonoids.
Mini Rev Med Chem. 2013;13:318-34.
Buss H, Chan TP, Sluis KB, Domigan NM, Winterbourn CC. Protein carbonyl
measurement by a sensitive ELISA method. Free Radic Biol Med. 1997;23:361-
6.
Chen JX, O'Mara PW, Poole SD, Brown N, Ehinger NJ, Slaughter JC, et al.
Isoprostanes as physiological mediators of transition to newborn life: novel
mechanisms regulating patency of the term and preterm ductus arteriosus.
Pediatr Res. 2012;72:122-8.
Dahan A, Altman H. Food-drug interaction: grapefruit juice augments drug
bioavailability--mechanism, extent and relevance. Eur J Clin Nutr. 2004;58:1-9.
Dasuri K, Zhang L, Keller JN. Oxidative stress, neurodegeneration, and the
balance of protein degradation and protein synthesis. Free Radic Biol Med.
2012.
26. Dusse LM, Silva RM, Vieira LM, das Gracas Carvalho M. Does plasma nitrite
determination by the Griess reaction reflect nitric oxide synthesis? Clin Chim
Acta. 2005;362:195-7.
Ellman GL. Tissue Sulfhydryl Groups. Arch Biochem Biophys. 1959;82:70-7.
Ferry DR, Smith A, Malkhandi J, Fyfe DW, deTakats PG, Anderson D, et al.
Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence
for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996;2:659-68.
Greenacre SA, Ischiropoulos H. Tyrosine nitration: localisation, quantification,
consequences for protein function and signal transduction. Free Radic Res.
2001;34:541-81.
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first
enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130-9.
Ischiropoulos H. Protein tyrosine nitration--an update. Arch Biochem Biophys.
2009;484:117-21.
Kajimoto H, Hashimoto K, Bonnet SN, Haromy A, Harry G, Moudgil R, et al.
Oxygen activates the Rho/Rho-kinase pathway and induces RhoB and ROCK-1
expression in human and rabbit ductus arteriosus by increasing mitochondria-derived
reactive oxygen species: a newly recognized mechanism for sustaining
ductal constriction. Circulation. 2007;115:1777-88.
Kallapur SG, Kramer BW, Nitsos I, Pillow JJ, Collins JJ, Polglase GR, et al.
Pulmonary and systemic inflammatory responses to intra-amniotic IL-1alpha in
fetal sheep. Am J Physiol Lung Cell Mol Physiol. 2011;301:L285-95.
Kapadia V, Embers D, Wells E, Lemler M, Rosenfeld CR. Prenatal closure of
the ductus arteriosus and maternal ingestion of anthocyanins. J Perinatol.
2010;30:291-4.
Keller RL, Tacy TA, Fields S, Ofenstein JP, Aranda JV, Clyman RI. Combined
treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA) and
indomethacin increases ductus constriction in extremely premature newborns.
Pediatr Res. 2005;58:1216-21.
Levy R, Matitiau A, Ben Arie A, Milman D, Or Y, Hagay Z. Indomethacin and
corticosteroids: an additive constrictive effect on the fetal ductus arteriosus. Am
J Perinatol. 1999;16:379-83.
27. Linseisen J, Rohrmann S. Biomarkers of dietary intake of flavonoids and
phenolic acids for studying diet-cancer relationship in humans. Eur J Nutr.
2008;47 Suppl 2:60-8.
Marzocchella L, Fantini M, Benvenuto M, Masuelli L, Tresoldi I, Modesti A, et al.
Dietary flavonoids: molecular mechanisms of action as anti- inflammatory
agents. Recent Pat Inflamm Allergy Drug Discov. 2011;5:200-20.
Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein):
recent advances and clinical relevance. Clin Pharmacol Ther.
2004;75:13-33.
Medina-Remon A, Barrionuevo-Gonzalez A, Zamora-Ros R, Andres-Lacueva
C, Estruch R, Martinez-Gonzalez MA, et al. Rapid Folin-Ciocalteu method using
microtiter 96-well plate cartridges for solid phase extraction to assess urinary
total phenolic compounds, as a biomarker of total polyphenols intake. Anal
Chim Acta. 2009;634:54-60.
Michelakis ED, Rebeyka I, Wu X, Nsair A, Thebaud B, Hashimoto K, et al. O2
sensing in the human ductus arteriosus: regulation of voltage-gated K+
channels in smooth muscle cells by a mitochondrial redox sensor. Circ Res.
2002;91:478-86.
Michelakis ED, Thebaud B, Weir EK, Archer SL. Hypoxic pulmonary
vasoconstriction: redox regulation of O2-sensitive K+ channels by a
mitochondrial O2-sensor in resistance artery smooth muscle cells. J Mol Cell
Cardiol. 2004;37:1119-36.
Middleton E, Jr., Kandaswami C, Theoharides TC. The effects of plant
flavonoids on mammalian cells: implications for inflammation, heart disease,
and cancer. Pharmacol Rev. 2000;52:673-751.
Milne GL, Yin HY, Brooks JD, Sanchez S, Roberts LJ, Morrow JD.
Quantification of F2-isoprostanes in biological fluids and tissues as a measure
of oxidant stress. Method Enzymol. 2007;433:113-26.
Mocatta TJ, Winterbourn CC, Inder TE, Darlow BA. The effect of gestational
age and labour on markers of lipid and protein oxidation in cord plasma. Free
Radic Res. 2004;38:185-91.
Moise KJ, Jr. Effect of advancing gestational age on the frequency of fetal
ductal constriction in association with maternal indomethacin use. Am J Obstet
Gynecol. 1993;168:1350-3.
28. O'Donnell VB, Eiserich JP, Chumley PH, Jablonsky MJ, Krishna NR, Kirk M, et
al. Nitration of unsaturated fatty acids by nitric oxide-derived reactive nitrogen
species peroxynitrite, nitrous acid, nitrogen dioxide, and nitronium ion. Chem
Res Toxicol. 1999;12:83-92.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by
thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.
Paglia DE, Valentine WN. Studies on the quantitative and qualitative
characterization of erythrocyte glutathione peroxidase. J Lab Clin Med.
1967;70:158-69.
Paladini D, Marasini M, Volpe P. Severe ductal constriction in the third-trimester
fetus following maternal self-medication with nimesulide. Ultrasound Obstet
Gynecol. 2005;25:357-61.
Poston L, Igosheva N, Mistry HD, Seed PT, Shennan AH, Rana S, et al. Role of
oxidative stress and antioxidant supplementation in pregnancy disorders. Am J
Clin Nutr. 2011;94:1980S-5S.
Proteggente AR, Pannala AS, Paganga G, Van Buren L, Wagner E, Wiseman
S, et al. The antioxidant activity of regularly consumed fruit and vegetables
reflects their phenolic and vitamin C composition. Free Radic Res. 2002;36:217-
33.
Rasanen J, Jouppila P. Fetal Cardiac-Function and Ductus-Arteriosus during
Indomethacin and Sulindac Therapy for Threatened Preterm Labor - a
Randomized Study. American Journal of Obstetrics and Gynecology.
1995;173:20-5.
Reeve HL, Tolarova S, Nelson DP, Archer S, Weir EK. Redox control of oxygen
sensing in the rabbit ductus arteriosus. J Physiol-London. 2001;533:253-61.
Rice-Evans CA, Miller NJ. Antioxidant activities of flavonoids as bioactive
components of food. Biochem Soc Trans. 1996;24:790-5.
Romitelli F, Santini SA, Chierici E, Pitocco D, Tavazzi B, Amorini AM, et al.
Comparison of nitrite/nitrate concentration in human plasma and serum
samples measured by the enzymatic batch Griess assay, ion-pairing HPLC and
ion-trap GC-MS: The importance of a correct removal of proteins in the Griess
assay. J Chromatogr B. 2007;851:257-67.
29. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III
chronic prostatitis: A preliminary prospective, double-blind, placebo-controlled
trial. Urology. 1999;54:960-3.
Sivanandan S, Bali V, Soraisham AS, Harabor A, Kamaluddeen M.
Effectiveness and Safety of Indomethacin versus Ibuprofen for the Treatment of
Patent Ductus Arteriosus in Preterm Infants. Am J Perinatol. 2013.
Takahashi Y, Roman C, Chemtob S, Tse MM, Lin E, Heymann MA, et al.
Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in
vitro and in vivo (vol 48, R1496, 2000). Am J Physiol-Reg I. 2000;279:Ra3-Ra.
Tatsch E, Bochi GV, Pereira RD, Kober H, Agertt VA, de Campos MMA, et al. A
simple and inexpensive automated technique for measurement of serum
nitrite/nitrate. Clin Biochem. 2011;44:348-50.
Thebaud B, Michelakis ED, Wu XC, Moudgil R, Kuzyk M, Dyck JR, et al.
Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to
preterm rabbit and remodeled human ductus arteriosus: implications for infants
with patent ductus arteriosus. Circulation. 2004;110:1372-9.
Weber D, Kneschke N, Grimm S, Bergheim I, Breusing N, Grune T. Rapid and
sensitive determination of protein-nitrotyrosine by ELISA: Application to human
plasma. Free Radic Res. 2012;46:276-85.
Zamora-Ros R, Urpi-Sarda M, Lamuela-Raventos RM, Martinez-Gonzalez MA,
Salas-Salvado J, Aros F, et al. High urinary levels of resveratrol metabolites are
associated with a reduction in the prevalence of cardiovascular risk factors in
high-risk patients. Pharmacol Res. 2012;65:615-20.
Zielinsky P, Manica JL, Piccoli AL, Jr., Nicoloso LH, Barra M, Alievi MM, et al.
Fetal ductal constriction caused by maternal ingestion of green tea in late
pregnancy: an experimental study. Prenat Diagn. 2012a;32:921-6.
Zielinsky P, Piccoli AL, Jr., Manica JL, Nicoloso LH, Menezes H, Busato A, et
al. Maternal consumption of polyphenol-rich foods in late pregnancy and fetal
ductus arteriosus flow dynamics. J Perinatol. 2010;30:17-21.
Zielinsky P, Piccoli AL, Jr., Manica JL, Nicoloso LH, Vian I, Bender L, et al.
Reversal of fetal ductal constriction after maternal restriction of polyphenol-rich
foods: an open clinical trial. J Perinatol. 2012b;32:574-9.
30. Zilka N, Stozicka Z, Cente M, Kazmerova Z, Kovacech B, Novak M.
Immunomodulation of memory-impairing protein tau in Alzheimer's disease.
Neurodegener Dis. 2012;10:242-5.
31. Figure captions
Figure 1. Fetal Doppler echocardiography from sheep at the third trimester of
pregnancy after high polyphenol consumption. Bars represent systolic and
diastolic velocities (A) and the pulsatility index (B). Echocardiographical images
of the ductus arteriosus before (C) and after treatment (D). *Significant
differences in relation to basal (p<0.05, Student’s t-test). BT: before
treatment/basal; AT: after treatment.
Figure 2. Total polyphenol urinary excretion in pregnant sheep after dietary
supplementation with polyphenol-rich foods (PRF). *Significantly different from
basal (p<0.05, Mann-Whitney test). BT: before treatment/basal; AT: after
treatment.
Figure 3. Serum NOx levels in pregnant sheep submitted to high polyphenol
ingestion in the third trimester of pregnancy. *Significant difference in relation to
basal (p<0.05, Mann-Whitney test). BT: before treatment/basal; AT: after
treatment.
Figure 4. Associations between NOx levels and antioxidant enzymes. (A) GPx
versus NOx (r=-0.755, p=0.004, n=12) and (B) CAT versus NOx (r=-0.812,
p=0.001, n=12). Spearman’s rank used for both statistical correlations.
32. Figure 5. Associations of lipid damage with (A) NOx levels (r=0.748, p=0.005,
n=12) and (B) total polyphenol excretion (r=-0.622, p=0.030, n=12). Spearman’s
rank used for both statistical correlations.
Figure 6. Associations between NOx levels and fetal echocardiographical
parameters. (A) NOx versus SV (r=-0.853, p=0.0004, n=12), (B) NOx versus DV
(r=-0.705, p=0.010, n=12), (C) NOx versus PI (r=0.599, p=0.039, n=12).
Spearman’s rank used for all statistical correlations.
33. Tables
Table 1. Oxidative stress biomarkers in pregnant sheep submitted to high
polyphenol ingestion in the third trimester of pregnancy.
Biomarkers BT AT
TBARS (μmol L-1) 17.22 ± 2.05 12.53 ± 2.11*
3-NT (ρmol mg-1 protein) 5.34 ± 0.91 6.48 ± 2.02
PCO (nmol mg-1 protein) 1.09 ± 0.09 1.49 ± 0.31*
Nonprotein thiols (μmol mL−1 RBC) 0.11 ± 0.04 0.04 ± 0.01*
GPx (μmol NADPH min-1 mg-1
protein)
37.23 ± 11.19 62.96 ± 15.03*
GST (nmol CDNB-GSH min-1 mg-1
protein)
2.04 ± 1.03 1.38 ± 0.46
CAT (K CAT mg-1 protein) 0.69 ± 0.39 1.44 ± 0.33*
Results are shown as mean ± standard error. *Significant differences in relation
to basal (p<0.05). BT: before treatment/basal; AT: after treatment.
Table