scholarly journals GARLIC LOWERS BLOOD PRESSURE AND REDUCES OXIDATIVE STRESS BY INCREASING PLASMA H2S CONTENT IN PATIENTS WITH ARTERIAL HYPERTENSION

2020 ◽  
Vol 66 (4) ◽  
pp. 55-63
Author(s):  
O.M. Kravchuk ◽  
◽  
Yu.V. Goshovska ◽  
Yu.P. Korkach ◽  
V.F. Sagach ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Arterial Hypertension ◽  
Nitrosative Stress ◽  
Ros Generation ◽  
Full Spectrum ◽  
Old Patients ◽  
Inos Activity ◽  
Positive Effects ◽  
Production Of Hydrogen

Arterial hypertension (AH) is a multifactorial disease that is accompanied by the development of oxidative-nitrosative stress and insufficient production of hydrogen sulfide (H2S). We hypothesized that garlic bio supplement Full Spectrum Garlic (Swanson Health Product, USA) may be used as a potential H2S donor in treatment of AH in patients. The aim was to study the effect of garlic on blood pressure, ROS generation and cNOS/iNOS activity, biochemical in male 28-39 years old patients with grade II AH. It was found that 10 days of standard antihypertensive therapy (adrenoblockers, ACE inhibitors) with 30 days of garlic supplementation reduced mean systolic and diastolic pressures by 9 and 8 mm Hg respectively. Positive effects of garlic consumption on hemodynamic parameters were observed: enddiastolic volume increased by 8% and peripheral vascular resistance decreased by 11,3% . In the blood plasma of patients, H2S levels increased by 43,6% , the production of ROS and the content of lipid peroxidation products decreased significantly. It is important that the cNOS activity was increased by 130% and iNOS activity decreased by 38,3%. No significant changes in cholesterol, urea, creatinine, glucose, as well as erythrocyte parameters were observed, which indicates the tolerance of the garlic supplements. Thus, the hypotonic effect of garlic is realized by increasing endogenous H2S in plasma, improving endothelium-dependent relaxation of blood vessels and reducing the manifestations of oxidative stress, which makes it promising to use it in the complex therapy of hypertension.

Abstract 263: Differential Effects of 17ß-Estradiol and 16a-Hydroxyestrone in Oxidative Stress and Proliferative Responses in Human Pulmonary Artery Smooth Muscle Cells - Implications in Pulmonary Arterial Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Katie Y Hood ◽  
Augusto C Montezano ◽  
Margaret R MacLean ◽  
Rhian M Touyz
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Arterial Hypertension ◽  
Cell Growth ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Antioxidant Systems ◽  
Ros Generation ◽  
Ros Production ◽  
Differential Effects ◽  
Pulmonary Arterial

Women develop pulmonary arterial hypertension (PAH) more frequently than men. This may relate, in part, to metabolism of 17β-estradiol (E2), leading to formation of the deleterious metabolite, 16α-hydroxyestrone (16α OHE1), which plays a role in the remodelling of pulmonary arteries. Molecular mechanisms whereby 16αOHE1 influences PASMC remodelling are unclear but ROS may be important, since oxidative stress has been implicated in the pathogenesis of PAH. We hypothesised that E2 and 16αOHE1 leads to Nox-induced ROS production, which promotes PASMC damage. Cultured PASMCs were stimulated with either E2 (1nM) or 16αOHE1 (1nM) in the presence/absence of EHT1864 (100μM, Rac1 inhibitor) or tempol (antioxidant; 10μM). ROS production was assessed by chemiluminescence (O2-) and Amplex Red (H2O2). Antioxidants (thioredoxin, peroxiredoxin 1 and NQ01), regulators of Nrf2 (BACH1, Nrf2) and, marker of cell growth (PCNA) were determined by immunoblotting. E2 increased O2- production at 4h (219 ± 30% vs vehicle; p<0.05), an effect blocked by EHT1864 and tempol. E2 also increased H2O2 generation (152 ± 4%; p<0.05). Thioredoxin, NQ01 and peroxiredoxin1 (71 ± 6%; 78 ± 9%; 69 ± 8%; p<0.05 respectively) levels were decreased by E2 as was PCNA expression (72 ± 2%; p<0.05). 16αOHE1 exhibited a rapid (5 min) and exaggerated increase in ROS production (355 ± 41%; p<0.05), blocked by tempol and EHT1864. This was associated with an increase in Nox4 expression (139 ± 11% vs vehicle, p<0.05). 16αOHE1 increased BACH1, (129 ± 3%; p<0.05), a competitor of Nrf2, which was decreased (92 ± 2%). In contrast, thioredoxin expression was increased by 16aOHE1 (154 ± 22%; p<0.05). PCNA (150 ± 5%) expression was also increased after exposure to 16αOHE1. In conclusion, E2 and 16αOHE1 have differential effects on redox processes associated with PASMC growth. Whereas E2 stimulates ROS production in a slow and sustained manner without effect on cell growth, 16αOHE1 upregulates Nox4 with associated rapid increase in ROS generation and downregulation of antioxidant systems, affecting proliferation. Our findings suggest that E2 -derived metabolites may promote a pro-proliferative PASMC phenotype through Nox4-derived ROS generation. These deleterious effects may impact on vascular remodeling in PAH.

scholarly journals Fixed combination of lercanidipine with enalapril - pharmacological features, clinical feasibility, advantages in the treatment of hypertension

2021 ◽  
pp. 21-24
Author(s):  
P. О. Lazarev
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Arterial Hypertension ◽  
Fixed Combination ◽  
Antihypertensive Drugs ◽  
Mechanisms Of Action ◽  
High Efficacy ◽  
National Guidelines ◽  
Treatment Of Hypertension ◽  
And Oxidative Stress

According to current international and national guidelines for the management of arterial hypertension preference is given to the use of fixed combinations of antihypertensive drugs of different classes, thus increasing the effectiveness of therapy acting in a complementary manner to affect different pathogenic mechanisms of arterial hypertension and reducing the frequency of side effects. A fixed combination of lercanidipine and enalapril contains antihypertensive drugs that have complementary mechanisms of action. This combination effectively reduces blood pressure, has high efficacy and tolerability, it may provide an additive effect on macro- and microvascular structures, arterial stiffness and oxidative stress. It has a beneficial influence on renal function, especially in patients with comorbidities.

P4476Cardiovascular benefits of GLP-1 (liraglutide) treatment in experimental arterial hypertension are mediated by the endothelial GLP-1 receptor

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Steven ◽  
J Helmstaedter ◽  
K Filippou ◽  
F Pawelke ◽  
F Katie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Arterial Hypertension ◽  
Knockout Mice ◽  
Vascular Function ◽  
Myeloid Cell ◽  
Inflammatory Cells ◽  
Vascular Wall ◽  
Cardioprotective Effects ◽  
Vascular Oxidative Stress

Abstract Objective The LEADER trial demonstrated that glucagon-like peptide-1 (GLP-1) analogs like Liraglutide (Lira) reduce the risk of cardiovascular events in T2DM, an effect beyond glycemic control. A detailed evaluation of the precise mechanisms underlying the cardiovascular protective effects of GLP-1 has been hampered by the fact that the GLP-1 receptor is expressed on different cell types in the vasculature including platelets, neuronal, endothelial and inflammatory cells. We used endothelial and myeloid cell-specific knockout mice of the GLP-1 receptor (GLP-1r) in an angiotensin-II (ATII)-induced model of hypertension. The aim of the recent study was to investigate the cardioprotective effects of GLP-1 in ATII-induced arterial hypertension and to characterize the cell-specific contribution of GLP-1r signaling. Methods Arterial hypertension was induced by s.c. ATII administration (0.5mg/kg/d; 7 days) in WT (C57/BL6J) as well as endothelial and myeloid cell-specific GLP-1r knockout mice (Cdh5crexGLP-1rfl/fl and LysMcrexGLP-1rfl/fl mice). Animals were treated with Lira (2x30μg/d; 7 days). Blood pressure was measured by tail-cuff. Vascular function was tested by isometric tension recording. Aortic and cardiac tissue was used for Western blotting, qRT-PCR, FACS, IHC and HPLC to determine the extent of inflammation, oxidative stress and fibrosis. ELISA was used to determine GLP-1 and insulin levels in plasma. Results Endogenous GLP-1 (7–36 and 9–36) was reduced in hypertensive animals. Lira ameliorated blood pressure and improved endothelial dysfunction, vascular oxidative stress and inflammation caused by ATII, in both WT and myeloid cell-specific GLP-1r knockout mice. Hypertension led to infiltration of inflammatory monocytes (Ly6G-Ly6Chigh) and neutrophils (Ly6G+Ly6C+) into the vascular wall, which was prevented by Lira. In accordance, Lira suppressed vascular oxidative stress and mRNA expression of iNOS, CD11b and Nox2. Endothelial NO synthase (eNOS) was S-glutathionylated with ATII treatment indicating uncoupled eNOS. Thus, aortic NO levels were reduced, all of which was restored by Lira. Furthermore, vascular fibrosis and cardiac hypertrophy were tremendously reduced by GLP-1. Interestingly, all of these beneficial cardiovascular effects of GLP-1 were abolished in endothelial cell-specific GLP-1r knockout mice. Conclusion We show that Lira reduces blood pressure and improves vascular function, fibrosis and cardiac hypertrophy in experimental arterial hypertension in mice. Mechanistically, Lira prevents the infiltration of inflammatory cells to the vascular wall, leading to reduced oxidative stress and improved NO bioavailability. Beneficial effects of GLP-1 are mediated by the GLP-1r expressed on endothelial and not myeloid cells. With the present study we provide a mechanistic approach to explain the cardioprotective effects of GLP-1 analogs like Lira, for which the endothelial GLP-1 receptor is indispensable. Acknowledgement/Funding Deutsche Forschungsgesellschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF)

scholarly journals The Involvement of a Polyphenol-Rich Extract of Black Chokeberry in Oxidative Stress on Experimental Arterial Hypertension

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Manuela Ciocoiu ◽  
Laurentiu Badescu ◽  
Anca Miron ◽  
Magda Badescu
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Arterial Hypertension ◽  
Ethanolic Extract ◽  
Nutritional Supplement ◽  
Ionization Mass ◽  
Noninvasive Blood Pressure ◽  
Pressure System ◽  
Total Antioxidant ◽  
Black Chokeberry

The aim of this study is to characterize the content ofAronia melanocarpaElliott (black chokeberry) extract and also to estimate the influence of polyphenolic compounds contained in chokeberries on oxidative stress, on an L-NAME-induced experimental model of arterial hypertension. The rat blood pressure values were recorded using a CODA Noninvasive Blood Pressure System. HPLC/DAD coupled with ElectroSpray Ionization-Mass Spectrometry allowed identification of five phenolic compounds in berries ethanolic extract as follows: chlorogenic acid, kuromanin, rutin, hyperoside, and quercetin. The serous activity of glutathione-peroxidase (GSH-Px) has significantly lower values in the hypertensive (AHT) group as compared to the group protected by polyphenols (AHT + P). The total antioxidant capacity (TAC) values are lower in the AHT group and they are significantly higher in the AHT + P group. All the measured blood pressure components revealed a biostatistically significant blood pressure drop between the AHT group and the AHT + P group. The results reveal the normalization of the reduced glutathion (GSH) concentration as well as a considerable reduction in the malondialdehyde (MDA) serum concentration in the AHT + P group. Ethanolic extract of black chokeberry fruits not only has a potential value as a prophylactic agent but also may function as a nutritional supplement in the management of arterial hypertension.

CONTRADICTORY PROPERTIES OF URIC ACID AND ASPECTS OF THE BIOCHEMISTRY OF ARTERIAL HYPERTENSION

2020 ◽  
pp. 78-80
Author(s):  
Bezbabicheva T.S.
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Uric Acid ◽  
Arterial Hypertension ◽  
Human Serum ◽  
Serum Uric Acid ◽  
Human Body ◽  
Human Population ◽  
Antioxidant Properties ◽  
Evolutionary Advantage

Uric acid is a product of purine catabolism. The manifestation of hyperuricemia (an increase in the amount of uric acid in the blood) for cells and the entire human body is being studied in connection with new data on the properties of this molecule. Relatively recently, interest in uric acid has ceased to be limited to the "disease of kings" - gout. Currently, more and more studies are investigating the contradictory relationship between uric acid and hypertension. It is believed that uric acid may be involved in the development of oxidative stress, which plays an important role in increasing blood pressure. The argument against this is the strong antioxidant properties of uric acid. It is such an important utilizer of peroxynityrite that it has even given an evolutionary advantage to the human population (unlike other mammals, human serum uric acid concentrations are much higher and normally range from 3 mg / DL to 6 mg / DL). Complex and multidirectional.

scholarly journals Gardening Intervention as a Low- to Moderate-Intensity Physical Activity for Improving Blood Lipid Profiles, Blood Pressure, Inflammation, and Oxidative Stress in Women over the Age of 70: A Pilot Study

HortScience ◽  
2017 ◽  
Vol 52 (1) ◽  
pp. 200-205 ◽  
Author(s):  
Sin-Ae Park ◽  
A-Young Lee ◽  
Hee-Geun Park ◽  
Ki-Cheol Son ◽  
Dae-Sik Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Physical Activity ◽  
Blood Pressure ◽  
Blood Lipid ◽  
Lipid Profiles ◽  
Moderate Intensity ◽  
Community Center ◽  
Moderate Physical Activity ◽  
Positive Effects ◽  
And Oxidative Stress

The objective of this study was to investigate the effects of a gardening intervention as a physical activity in women aged over 70 years. Twenty-one women aged over 70 years were recruited from the community in Seoul, South Korea. Eleven subjects at a senior community center participated in a 15-session gardening program (twice a week, average 50 minutes per session) from Sept. to Nov. 2015. The rest of the subjects who were recruited from another senior community center acted as the control group. Blood lipid profiles, blood pressure, inflammation in peripheral-blood mononuclear cells (PBMC), and oxidative stress were assessed by a blood test before and after the 15-session gardening intervention. The results showed that the subjects in the gardening intervention as a low- to moderate-physical activity had a significant improvement in their high-density lipoprotein (HDL) level, systolic and diastolic blood pressures, and the variables related to immunity such as tumor necrosis factor-α (TNF-α) for inflammation in blood and receptor for advanced glycation end products (RAGE) expression for oxidative stress. The results of this study suggested that the 15-session gardening intervention as a low- to moderate-physical activity led to positive effects on the blood lipid profiles, blood pressure, level of inflammatory markers in blood, and oxidative stress of women aged over 70 years.

scholarly journals Effects of Dietary Strategies on Exercise-Induced Oxidative Stress: A Narrative Review of Human Studies

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 542
Author(s):  
Zhen Zeng ◽  
Christoph Centner ◽  
Albert Gollhofer ◽  
Daniel König
Keyword(s):  
Oxidative Stress ◽  
Narrative Review ◽  
Ros Generation ◽  
Positive Effects ◽  
Stress Markers ◽  
Current State ◽  
State Of Research ◽  
Exercise Induced ◽  
Dietary Strategies ◽  
Antioxidant Effects

Exhaustive exercise can induce excessive generation of reactive oxygen species (ROS), which may enhance oxidative stress levels. Although physiological levels are crucial for optimal cell signaling and exercise adaptations, higher concentrations have been demonstrated to damage macromolecules and thus facilitate detrimental effects. Besides single dosages of antioxidants, whole diets rich in antioxidants are gaining more attention due to their practicality and multicomponent ingredients. The purpose of this narrative review is to summarize the current state of research on this topic and present recent advances regarding the antioxidant effects of whole dietary strategies on exercise-induced oxidative stress in humans. The following electronic databases were searched from inception to February 2021: PubMed, Scope and Web of Science. Twenty-eight studies were included in this narrative review and demonstrated the scavenging effects of exercise-induced ROS generation, oxidative stress markers, inflammatory markers and antioxidant capacity, with only one study not confirming such positive effects. Although the literature is still scarce about the effects of whole dietary strategies on exercise-induced oxidative stress, the majority of the studies demonstrated favorable effects. Nevertheless, the protocols are still very heterogeneous and further systematically designed studies are needed to strengthen the evidence.

Abstract 113: Glucose Metabolic Disorders in Aging-Associated Microglial NADPH Oxidase 2 Activation and Oxidative Damage of Cerebral Microvasculature and Neurons

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Li Geng ◽  
Jian-Mei Li
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Metabolic Disorders ◽  
Aging Brain ◽  
Ros Generation ◽  
Ros Production ◽  
The Brain

Aging has been recognised to be a major risk factor for the development of cardiovascular and neurodegenerative diseases and growing evidence suggests a role for oxidative stress. A Nox2-containing NADPH oxidase has been reported to be a major source of reactive oxygen species (ROS) generation in the vascular system and in the brain. However, the role of Nox2 enzyme in aging-related metabolic disorders and vascular neurodegeneration remains unclear. In this study, we used age-matched wild-type (WT) and Nox2-deficient (Nox2 -/- ) mice on a C57BL/6 background at young (3-4 month) and aging (20-24 month) to investigate the role of Nox2 in aging-related oxidative stress, metabolic disorders and cerebral vascular dysfunction. There was an aging-related increase in blood pressure in WT mice (126 mmHg for young and 148 mmHg for aging) (P<0.05); however the blood pressure was well maintained without significant change in Nox2 -/- aging mice. Compared to young WT mice, WT aging mice had significantly high levels of fasting serum insulin and this was accompanied with delayed clearance of glucose (P<0.05) indicating insulin resistance. In contrast, there was no indication of insulin resistance for Nox2 -/- aging mice. We then examined aging-related brain oxidative stress. Compared to WT young mice, there were significant increases (2.7±0.7 folds) in the levels of ROS production by WT aging brain tissue homogenates as detected by lucigenin-chemiluminescence and DHE fluorescence. Increased ROS production in WT aging brain was accompanied by a significant increase (1.8±0.3 folds) in the Nox2 expression detected mainly in the microglial cells (labelled by Iba-1) and decreases in brain capillaries (labelled by CD31) (2.4±0.8 folds) and neurons (labelled by Neu-N) (2.9±0.5 folds) (all P<0.05). Knockout of Nox2 abolished aging-associated increases in brain ROS production and significantly reduced the aging-related pathophysiological changes in the brain. In conclusion, aging-associated metabolic disorders play a crucial role in aging-associated Nox2 activation and vascular neurodegeneration. Nox2-containing NADPH oxidase represents a valuable therapeutic target for oxidative stress-related brain microvascular damage and neurodegeneration.

scholarly journals Increased Nitro-Oxidative Stress Toxicity as a Major Determinant of Increased Blood Pressure in Mood Disorders

2020 ◽  
Author(s):  
Kamila Landucci Bonifacio ◽  
Décio Sabbatini Barbosa ◽  
Estefânia Gastaldello Moreira ◽  
Carine Farias Coneglian ◽  
Heber Odebrecht Vargas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Mood Disorders ◽  
Nitrosative Stress ◽  
Protein Body ◽  
Resistance Index ◽  
Atherogenic Index ◽  
Lipid Hydroperoxides ◽  
Healthy Controls

Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&amp;NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. Results: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&amp;NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. Conclusions: Activated O&amp;NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.

scholarly journals The effects of quercetin on seizure, inflammation parameters and oxidative stress in acute on chronic tramadol intoxication

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samaneh Nakhaee ◽  
Khadijeh Farrokhfall ◽  
Ebrahim Miri-Moghaddam ◽  
Mohsen Foadoddini ◽  
Masoumeh Askari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Single Dose ◽  
Nitrosative Stress ◽  
Biological Effects ◽  
Chronic Administration ◽  
The Body ◽  
Kidney Cortex ◽  
Control Group ◽  
Positive Effects ◽  
Group I

Abstract Background Tramadol is a widely used synthetic opioid for moderate to severe pain. Some studies have shown that tramadol can increase oxidative stress in different tissues of the body. Quercetin is also a substance with various biological effects, including antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, and cardioprotective activities. The current investigation aimed at determining the effects of quercetin, with or without naloxone, on tramadol intoxication. Methods This study was performed on 30 male Wistar rats divided into five groups: Group I) control group: intraperitoneal injections of normal saline 0.9% for 14 days; Group II) tramadol: 25 mg/kg for 14 days, and then a 50 mg/kg acute dose injection on the last day; Group III) acute quercetin (single dose): tramadol injection as with the second group plus 100 mg/kg of quercetin on the last day; Group IV) chronic quercetin: tramadol injection similar to the second group plus quercetin 100 mg/kg for 14 days; Group V) quercetin plus naloxone: tramadol injection similar to the second group plus injection of quercetin 100 mg/kg + intravenous naloxone 2 mg/kg on the last day, followed by a 4 mg/kg/h injection of naloxone for six hours. The rats were monitored for six hours on the last day, relating to the number and severity of seizures. Finally, the samples were prepared for biochemical investigation of the serum level of oxidative stress markers (MDA, SOD, NOx), inflammatory factors (IL-6, TNF-α), biochemical parameters (ALT, AST, creatinine, glucose) and hematological assay. The liver, heart, kidney, cortex, cerebellum, and adrenal tissues were collected to investigate the redox state. Results None of the treatments had positive effects on the number and severity of seizures. Chronic administration of quercetin led to alteration of some blood parameters, including reduced hemoglobin level and elevated platelet counts. Acute on chronic tramadol administration resulted in a significant rise in AST, where different treatments failed to reduce their levels down to the control group. Conclusion chronic administration of quercetin showed decreased oxidative/nitrosative stress in the liver, kidney, adrenal, and heart tissues. Quercetin plus naloxone decreased oxidative stress in the heart and adrenal tissues, but adverse effects on the brain cortex and hepatic function. Single-dose quercetin reduced cardiac oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document