Abstract 66: Ascorbate Prevents Hypertension, Proteinuria and Concentric Hypertrophy by Balancing the Nitroso-redox System in a Model of Preeclampsia, the S-nitrosoglutathione Reductase (gsnor) Deficient Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Raul A Dulce ◽  
Rosemeire K Takeuchi ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Nitrosative Stress ◽  
Fluorescent Dyes ◽  
Protein S ◽  
Redox System ◽  
Fetal Mortality ◽  
Mortality And Morbidity ◽  
Redox Imbalance ◽  
Concentric Hypertrophy ◽  
Maternal Hypertension ◽  
And Control

Introduction: Preeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by increased levels of reactive oxygen species (ROS) and S-nitrosylated protein, and decreased levels of the antioxidant, ascorbate (Asc). Mice lacking S-nitrosoglutathione reductase (GSNOR –/– ), a denitrosylase that regulates protein S-nitrosylation, exhibit a PE-like phenotype including maternal hypertension, proteinuria, cardiac concentric hypertrophy and impaired placental vascularization. We hypothesize that the PE-like phenotype is mediated by nitroso-redox imbalance and nitrosative stress and can be rescued with ascorbate treatment. Methods: Pregnant GSNOR –/– and control (WT) mice (n=5-7) were provided drinking water ± Asc beginning at day 0.5 of gestation (E0.5). We determined blood pressure using a Millar catheter, relative wall thickness (RWT) by echocardiography, and placental vascularization by isolectin staining. Cardiomyocytes (CM) were isolated at late stage pregnancy (E17.5) and fluorescent dyes used to determine levels of ROS (2’7’-dichlorofluorescein), nitric oxide (NO, diaminofluorescin) and peroxynitrite (dihydrorhodamine 123). Results: Isolated CMs from pregnant GSNOR –/– hearts, exhibited elevated levels of ROS (2.48±0.39 vs. 1.58±0.18 ΔF/F 0 ), free NO (6.65±0.43 vs. 5.59±0.26 ΔF/F 0 ) and peroxynitrite (0.75±0.04 vs. 0.39±0.03 ΔF/F 0 ) compared to WT. These increases were prevented with Asc treatment (P<0.01), which completely rescued the PE phenotype in GSNOR –/– mothers, including hypertension (105±2 mmHg vs. 95± mmHg in Asc-treated, P<0.05), proteinuria (P<0.05) and RWT (0.56±0.04 vs. 0.45±0.03 in Asc-treated (P<0.05). Placental vascularization was also significantly improved with Asc treatment in GSNOR –/– mothers. Asc had no significant effect in WT mice. Conclusion: Our findings indicate that nitroso-redox imbalance and nitrosative stress contributes to PE in mice. Asc treatment balanced the nitroso-redox system and rescued the pathological phenotypes in GSNOR –/– mice, suggesting that it can be used therapeutically to treat or prevent preeclampsia.

scholarly journals S-nitrosoglutathione reductase deficiency causes aberrant placental S-nitrosylation and preeclampsia

2020 ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Raul A Dulce ◽  
Christopher I Murray ◽  
Michael A Bellio ◽  
Julia Fritsch ◽  
...  
Keyword(s):  
Nitrosative Stress ◽  
Protein S ◽  
Fetal Mortality ◽  
Oxygen Species ◽  
Fetal Growth Retardation ◽  
Amino Acid Residues ◽  
Mortality And Morbidity ◽  
Therapeutic Implications ◽  
Concentric Hypertrophy ◽  
The Difference

ABSTRACTPreeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by an increase in S-nitrosylated (SNO) proteins and reactive oxygen species (ROS), suggesting a pathophysiologic role for dysregulation in nitrosylation and nitrosative stress. Here we show that mice lacking S-nitrosoglutathione reductase (GSNOR−/−), a denitrosylase regulating protein S-nitrosylation, exhibit a PE phenotype, including hypertension, proteinuria, renal pathology, cardiac concentric hypertrophy, decreased placental vascularization, and fetal growth retardation. ROS, nitric oxide (NO) and peroxynitrite levels are elevated. Importantly, mass spectrometry reveals elevated placental SNO-amino acid residues in GSNOR−/−mice. Ascorbate reverses the phenotype except for fetal weight, reduces the difference in the S-nitrosoproteome, and identifies a unique set of SNO-proteins in GSNOR−/−mice. Importantly, the human preeclamptic placenta exhibits decreased GSNOR activity and increased nitrosative stress. Therefore, deficiency of GSNOR creates dysregulation of placental S-nitrosylation and preeclampsia in mice, which can be rescued by ascorbate. Coupled with similar findings in human placentas, these findings offer valuable insights and therapeutic implications for PE.

Abstract 238: S-nitrosoglutathione Reductase (GSNOR) Plays a Critical Role in Placental Vascularization Working Through the VEGF-NO Pathway

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Michael A Bellio ◽  
Julia Fritsch ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Nitrosative Stress ◽  
Critical Role ◽  
Late Pregnancy ◽  
Protein S ◽  
Capillary Density ◽  
Fetal Mortality ◽  
Mortality And Morbidity ◽  
Working Through ◽  
Concentric Hypertrophy ◽  
Enos Protein

Introduction: Preeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by increased levels of reactive oxygen species (ROS) and S-nitrosylated protein, and decreased levels of the antioxidant, ascorbate (Asc), which is required for the release of nitric oxide (NO) from nitrosylated proteins. Mice lacking S-nitrosoglutathione reductase (GSNOR –/– ), a denitrosylase that regulates protein S-nitrosylation, exhibit a PE-like phenotype including maternal hypertension, cardiac concentric hypertrophy and impaired placental vascularization. We hypothesized that impaired placental vascularization, one of the primary causes of preeclampsia is mediated by alteration in S-nitrosylation of the VEGF-NO pathway, and ascorbate treatment rescues this pathologic phenotype. Methods: Pregnant GSNOR –/– and control (WT) mice (n=5-7) were studied at late pregnancy (day 17.5). Ascorbate was provided in drinking water beginning at day 0.5. Fetoplacental capillary density was determined from isolectin staining and reactive nitrosative stress determined from nitrotyrosine staining in placental sections. S-nitrosylation of VEGF was determined using SNO-Rac and eNOS levels by Western blot analysis. Results: Fetoplacental capillary density was reduced 19% in GSNOR –/– fetuses compared to WT (P<0.001). GSNOR –/– placentas exhibited higher nitrotyrosine staining than WT placentas, indicating the presence of nitrosative stress. These increases were associated with reduced level of eNOS protein (P<0.05) and decreased S-nitrosylation of VEGF (P<0.05) in the GSNOR –/– placentas as compared to WT. Ascorbate treatment decreased nitrotyrosine staining, and increased fetoplacental capillary density ~10% (P<0.001), eNOS protein levels (P<0.05) and S-nitrosylation of VEGF (P<0.05) in the GSNOR –/– placentas as compared to WT. Conclusion: These findings suggest that GSNOR plays an essential role in promoting placental vascularization in part working through the VEGF-NO pathway. Ascorbate treatment rescued the nitrosative stress and improved placental vascularization, suggesting that it can be used therapeutically to treat or prevent preeclampsia.

scholarly journals MANAGEMEN KELELAHAN SAAT PERSALINAN MENGGUNAKAN JUS SEMANGKA

2018 ◽  
Vol 12 (1) ◽  
pp. 19
Author(s):  
Islah Wahyuni
Keyword(s):  
Post Partum ◽  
Fetal Mortality ◽  
Control Group ◽  
Normal Delivery ◽  
Mortality And Morbidity ◽  
Watermelon Juice ◽  
Before And After ◽  
The Difference ◽  
Lactate Levels ◽  
And Control

<em>The condition of fatigue during labor has received little attention for meditative intervention, so it is important in suppressing the adverse effects of fatigue during labor on the mother and fetus, and preventing the incidence of maternal and fetal mortality and morbidity. The purpose of the study to determine the handling of fatigue using watermelon juice in maternal mothers. Anaerobic fatigue was measured using blood lactic acid values, and Visual Analoque Scale-Fatique (VAS-F) quetioner from 68 respondents were divided into 2 groups: treatment and control group were selected concencutive sampling.  Measurement of blood lactate level was performed 2x at before and after treatment. Data analysis was using univariate and bivariate by dependent T test. The results showed that there were significant differences between lactate levels before and after treatment and control group (.003). The VAS-Fatique analysis resulted  the difference in fatigue experienced stage 1 (.015) and  fatigue experienced 24 hour post partum (.001) is lower treatment group compared with the control group. In conclusion, watermelon juice is effective as fatigue handling in maternal mothers, it is recommended that watermelon juice be given to the mother during normal delivery</em>

scholarly journals RISK FACTORS OF PREECLAMPSIA IN ANUTAPURA GENERAL HOSPITAL PALU CITY

2019 ◽  
Vol 2 (03) ◽  
pp. 110-114
Author(s):  
Nur Rosmala ◽  
Abd. Rahman ◽  
Nila Sintya Dewi ◽  
Nurul Fitria Aras ◽  
Pitriani .
Keyword(s):  
Risk Factors ◽  
Antenatal Care ◽  
Pregnant Women ◽  
Secondary Data ◽  
Sampling Technique ◽  
Fetal Mortality ◽  
Control Group ◽  
Mortality And Morbidity ◽  
Control Approach ◽  
And Control

Preeclampsia is one of the main causes of maternal and fetal mortality and morbidity. The purpose of this study was to determine the risk factors for preeclampsia in pregnant women at Anutapura Hospital Palu. This study was observational analytic with a case control approach. The case subjects were pregnant women who experienced preeclampsia and the control group were pregnant women who did not experience preeclampsia. Case samples were 112 and control 112 with matching age. Sampling is done by purposive sampling technique. Data sources used secondary data, medical records 2017. The results showed that parity (OR = 3,389 and CI = 1,936-5,934), complete antenatal care (OR = 4,012 and CI = 2,293-7,020), history of hypertension (OR = 5,071 and CI = 2,819-9,120) is a risk factor for preeclampsia in pregnant women. To overcome the incidence of preeclampsia antenatal care is expected to be more active in providing information about pregnancies that are at high risk of developing preeclampsia in pregnant women.

scholarly journals Oxygen Is Instrumental for Biological Signaling: An Overview

Oxygen ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 3-15
Author(s):  
John T. Hancock
Keyword(s):  
Oxidative Stress ◽  
Superoxide Anion ◽  
Nitrosative Stress ◽  
Redox Status ◽  
Complex Interplay ◽  
Wide Range ◽  
Form Part ◽  
High Concentrations ◽  
And Control ◽  
Signaling Components

Control of cellular function is extremely complex, being reliant on a wide range of components. Several of these are small oxygen-based molecules. Although reactive compounds containing oxygen are usually harmful to cells when accumulated to relatively high concentrations, they are also instrumental in the control of the activity of a myriad of proteins, and control both the upregulation and downregulation of gene expression. The formation of one oxygen-based molecule, such as the superoxide anion, can lead to a cascade of downstream generation of others, such as hydrogen peroxide (H2O2) and the hydroxyl radical (∙OH), each with their own reactivity and effect. Nitrogen-based signaling molecules also contain oxygen, and include nitric oxide (NO) and peroxynitrite, both instrumental among the suite of cell signaling components. These molecules do not act alone, but form part of a complex interplay of reactions, including with several sulfur-based compounds, such as glutathione and hydrogen sulfide (H2S). Overaccumulation of oxygen-based reactive compounds may alter the redox status of the cell and lead to programmed cell death, in processes referred to as oxidative stress, or nitrosative stress (for nitrogen-based molecules). Here, an overview of the main oxygen-based molecules involved, and the ramifications of their production, is given.

Protein synthesis is required for rapid degradation of tubulin mRNA and other deflagellation-induced RNAs in Chlamydomonas reinhardi

1986 ◽  
Vol 6 (1) ◽  
pp. 54-61
Author(s):  
E J Baker ◽  
L R Keller ◽  
J A Schloss ◽  
J L Rosenbaum
Keyword(s):  
Protein Synthesis ◽  
Transcriptional Control ◽  
Protein S ◽  
Protein Synthesis Inhibitors ◽  
Control Factors ◽  
Flagellar Proteins ◽  
The Stability ◽  
And Control

After flagellar detachment in Chlamydomonas reinhardi, there is a rapid synthesis and accumulation of mRNAs for tubulin and other flagellar proteins. Maximum levels of these mRNAs (flagellar RNAs) are reached within 1 h after deflagellation, after which they are rapidly degraded to their predeflagellation levels. The degradation of alpha- and beta-tubulin RNAs was shown to be due to the shortening of their half-lives after accumulation (Baker et al., J. Cell Biol. 99:2074-2081, 1984). Deflagellation in the presence of protein synthesis inhibitors results in the accumulation of tubulin and other flagellar mRNAs by kinetics similar to those of controls. However, unlike controls, in which the accumulated mRNAs are rapidly degraded, these mRNAs are stabilized in cycloheximide. The stabilization by cycloheximide is specific for the flagellar mRNAs accumulated after deflagellation, since there is no change in the levels of flagellar mRNAs in nondeflagellated (uninduced) cells in the presence of cycloheximide. The kinetics of flagellar mRNA synthesis after deflagellation are shown to be the same in cycloheximide-treated and control cells by in vivo labeling and in vitro nuclear runoff experiments. These results show that protein synthesis is not required for the induced synthesis of flagellar mRNAs, and that all necessary transcriptional control factors are present in the cell before deflagellation, but that protein synthesis is required for the accelerated degradation of the accumulated flagellar mRNAs. Since cycloheximide prevents the induced synthesis and accumulation of flagellar proteins, it is possible that the product(s) of protein synthesis required for the accelerated decay of these mRNAs is a flagellar protein(s). The possibility that one or more flagellar proteins autoregulate the stability of the flagellar mRNAs is discussed.

scholarly journals Perinatal Findings in Pregnancy Induced Hypertension: A Study in a Tertiary Teaching Hospital in Dhaka City

2017 ◽  
Vol 2 (1) ◽  
pp. 10-13
Author(s):  
Zobaida Sultana Susan ◽  
Surayea Bulbul ◽  
Jannat Ara Ferdows ◽  
Abu Nayeem
Keyword(s):  
Cross Sectional Study ◽  
Fetal Mortality ◽  
Pregnancy Induced Hypertension ◽  
College Hospital ◽  
Cross Sectional ◽  
Mortality And Morbidity ◽  
Tertiary Teaching ◽  
Induced Hypertension ◽  
Questionnaire Result ◽  
In Pregnancy

Background: Hypertensive disorders are common complication occurring during pregnancy which are responsible for maternal and fetal mortality and morbidity. Objective: The purpose of the present study was to determine the perinatal outcome in pregnancy induced hypertension. Methodology: This study was designed as cross-sectional study and was conducted from April 2013 to September 2013 for a period of six (06) moths. Patients admitted in the Department of Obstetrics and Gynaecology at Shaheed SuhrawardyMedical College Hospital, Dhaka. Data were collected by interview, physical examintions (blood pressure, pulse rate, oedema, heart and lungs auscultation) and lab investigations using a structural questionnaire. Result: Majority of the women belonged to age group 21-25 year. Maximum were (56%) primigravida. The mean gestational age was 34.6 weeks with the range from 28 to 40 weeks. Hyperurecaemia was frequent among patients with pregnancy induced hypertension. Intrauterine growth retardation (IUGR) was secondary to pregnancy induced hypertension which was associated with significantly increased perinatalmortality. Conclusion: In this study, prematurity is frequent in pregnancy induced hypertension and convulsion in nonresponsive patients is associated with significantly increased perinatal mortality.Journal of National Institute of Neurosciences Bangladesh, January 2016;2(1): 10-13

scholarly journals Cardiovascular and Neurological Complications Associated with Atrial Fibrillation

2017 ◽  
pp. 164-72
Author(s):  
Raymond Pranata ◽  
Hadrian Deka ◽  
Bambang Budi Siswanto
Keyword(s):  
Atrial Fibrillation ◽  
Cognitive Decline ◽  
Cardiovascular Mortality ◽  
Neurological Complications ◽  
Mortality And Morbidity ◽  
Major Cardiovascular Events ◽  
Bidirectional Association ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
And Control

Atrial fibrillation (FA) is the most common type of sustained-arrhythmia and one of the leading causes of mortality and morbidity globally, with estimated five million incidents. FA was associated with increased all-cause mortality (RR 1.46), cardiovascular mortality (RR 2.03), major cardiovascular events (RR 1.96), stroke (RR 2.42), ischemic stroke (RR 2.33), dementia (HR 1.42) and cognitive decline, ischemic heart disease (RR 1.61), sudden cardiac death (RR 1.88), heart failure (RR 4.99), chronic kidney disease (RR 1.64), and peripheral artery disease (RR 1.31). Overall, all-cause and cardiovascular mortality increased. Cognitive decline and dementia are also a concern since they impair function and quality of life. Overall, FA has bidirectional association with other cardiovascular diseases hence it acts as a marker for them. Therefore, prevention and control of risk factors are of utmost importance.

scholarly journals Venous Thromboembolic Disease and Bone Marrow Transplant: A Remarkable Cause of Mortality and Morbidity — Potentially Preventable

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5070-5070
Author(s):  
Marta Rivas Luque ◽  
Estefanía Morente Constantin ◽  
Pablo Romero Garcia ◽  
Maria Almudena Garcia-Ruiz ◽  
Manuel Jurado
Keyword(s):  
Medical History ◽  
Conflicts Of Interest ◽  
Protein S ◽  
Marrow Transplant ◽  
Morbidity And Mortality ◽  
Hematopoietic Stem ◽  
Mortality And Morbidity ◽  
Vein Thrombosis ◽  
Venous Thromboembolic ◽  
Hemorrhagic Risk

Abstract Thrombotic events are frequent in patients undergoing HSCT, being an important cause of morbidity and mortality. The highest incidence occurs three months after the transplant. There are several risk factors, which add to those already known for VTE: neoplasia, central venous catheters, immobilization, chemotherapy, infections, GVHD. In the series described, the frequencies are variable, between 0.5 and 23.5%, with an overall incidence of 5%. In patients with GVHD, this incidence increases, with up to 35% of events. METHODS A retrospective observational study that includes patients transplanted in our Unit between 2014 and 2017 has been conducted, with the objective of analyzing the incidence of VTE peri-TPH. Likewise, we have analyzed if it is associated to catheter, presence of CVRF, if there was a known medical history of thrombophilia, number of platelets at time of thrombosis, the heparin used and whether anticoagulation was maintained indefinitely or not. RESULTS Out of the 235 patients included in our series, 130 underwent an autologous transplant and 105 an allogeneic transplant. 18 thrombotic events occurred (9 men and 9 women, aged between 18 and 65 years), which means 7.5% (14 occurred between days 0-100, 12 in patients undergoing autologous hematopoietic stem cell transplantation). Three of them had thromboembolism and the rest deep vein thrombosis, 4 of which with catheter. The platelet count at the time of the event ranges from 21 to 409,000 / mm3. Regarding the heparin used, 2 were treated with Tinzaparin and the rest with Bemiparin. Only 1 of the patients presented prior VTE. Among the patients, there were some with CVRF and others without relevant medical history. Just in one patient, a family thrombophilia study had been performed prior to his hematological diagnosis, resulting in a deficit of protein S. In 8 of the patients, anticoagulation was maintained indefinitely with LMWH in the post-transplant period. CONCLUSIONS Our incidence approaches the literature, albeit the series of published cases are heterogeneous and with variable differences. Although the incidence of thrombosis in these patients is a cause of marked morbidity and mortality, the risk of bleeding also increases, therefore routine prophylaxis is not recommended in all patients. We must undergo an exhaustive analysis of the data to identify individually which patients may be candidates for prophylaxis, with the aim of reducing the incidence without raising the hemorrhagic risk of our patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Perceptions of caregivers on immunization in Ntungamo district, Uganda

2021 ◽  
Vol 8 (12) ◽  
pp. 5729
Author(s):  
Byamukama Topher ◽  
Keraka M. Margaret ◽  
Gitonga Eliphas
Keyword(s):  
Risk Factor ◽  
Intervention Group ◽  
Cost Effective ◽  
Systematic Sampling ◽  
Control Group ◽  
Post Intervention ◽  
Mortality And Morbidity ◽  
Significant Difference ◽  
Quasi Experimental ◽  
And Control

Background: Immunization is one of the most cost-effective public health interventions to reduce child mortality and morbidity associated with infectious diseases. The objective of this study was to determine the perceptions of caregivers on immunization in Ntungamo district.Methods: Quasi-experimental study was used with health centres assigned to intervention and control groups. Purposive sampling was used to select the two counties where the study was done. Proportional sampling was done to get study samples from each health facility, while systematic sampling was done to get study participants. A total of 787 children from twelve health facilities provided the study sample. A post intervention evaluation was conducted to determine the effect of these interventions. Association of variables was tested using Mann Whitney U-test and Chi-square.Results: On benefits, most caregivers in the intervention group (85.3%) and in the control group (54.3%) regarded immunization as very highly and moderately beneficial to their children respectively. On risks, most caregivers in the intervention group (85.5%) and control group (43.1%) regarded the risk factor associated with immunization as very low and moderate respectively. From hypothesis testing, there was a significant difference on the perceived benefits and risks of immunization between the intervention and control group.Conclusions: Most caregivers in the intervention and control group regarded immunization as very highly beneficial and moderately to their children respectively. Most of the caregivers in the intervention and control group regarded the risk factor associated with immunization as very low and moderate respectively. 

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