P2536Protective effects of ultra-low-dose menopausal hormonal therapy on endothelium function in postmenopausal women

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S N Tolstov ◽  
I A Salov ◽  
A P Rebrov

Abstract Introduction This is the first pilot study to assess the functional state of the vascular wall in postmenopausal women on the background of ultra low-dose menopausal hormone therapy (MHT). Purpose To evaluate the protective effects on endothelial function of ultra-low-dose MHT 0.5 mg of 17β-estradiol (E2) and 0.25 mg of drospirenone (DRSP) in postmenopausal women. Methods The study included 115 previously examined postmenopausal women. Group 1 (n=25) included patients who started receiving MGT with DRSP during the menopausal transition; in the 2nd group (n=31), women who started receiving MGT with DRSP in the early postmenopausal period. Women of the 1st and 2nd groups made the transition to a combination of 0.5 mg E2/0.25 mg DRSP. The control group (n=59) of women not taking MGT. The duration of therapy is 1.0 (0.9; 1.2) years. The age of women was 56.8±1.6 years, 57.1±2.8 years and 57.3±1.7 years (p>0.05). Endothelium-dependent vasodilation (EDV) of the brachial artery, levels of endothelin-1 (ET-1), metabolites of nitric oxide (NO), asymmetric dimethylarginine (ADMA), von Willebrand factor antigen (vWF: Ag) in plasma were evaluated. Results In the control group EDV 8.6±5.1% of the original and 7.4±4.5% by the end of the study (p=0.08); in women of the 1st group 12.5±3.8% and 12.2±4.4; in women of the 2nd group11.1±8.5% and 10.5±0.2% (p=0.07 between women of the 1st and 2nd groups by the end of the study). The level of NO metabolites in women of the 1st group 43.4 (28.6; 45.9) at baseline and 40.7 (34.4; 41.5) μmol/l by the end of the study, in women of the 2nd group 38.8 (36.5; 44.9) and 35.2 (32.8; 38.9) μmol/l (p=0.04 between the women of the 1st and 2nd groups). In the control group 34.6 (30.4; 38.2) and 27.8 (24.5; 34.9) μmol/l (p<0.001 for women of the 1st and 2nd groups). In women of the 1st group a significant increase in ET-1 was detected from 1.02±0.26 initially to 1.18±0.24 fMol/ml by the end of the study; levels of vWF:Ag with 0.839 (0.695; 0.940) and 0.900 (0.782; 0.925) U/ml. The level of ADMA did not change significantly 0.43±0.10 and 0.45±0.10 μmol/L. In women of the 2nd group a significant increase ET-1 was detected from 1.08±0.42 to 1.29±0.59 fMol ml; vWF:Ag from 0.841 (0.718; 0.960) to 0.829 (0.811; 0.984) U/ml and ADMA from 0.43±0.10 to 0.48±0.15 μmol/l (p>0.05). In the the control group a significant increase in the level of ET-1 was observed from 1.40±0.43 to 1.74±0.34 fMol/ml by the end of the study; vWF levels:Ag 0.860 (0.743; 0.941) and 0.960 (0.850; 1.025) U/ml, ADMA 0.48±0.16 and 0.60±0.18 μmol/l (p<0.01 compared with women of the 1st and 2nd groups). Conclusions Revealed protective effects on endothelial function of ultra low-dose MHT in postmenopausal women. Early and prolonged MHT has an additional positive effect on the functional state of the vascular wall. Acknowledgement/Funding None

2020 ◽  
Vol 17 (9) ◽  
pp. 815-822
Author(s):  
Maryam Safary ◽  
Sevil Hakimi ◽  
Noushin Mobaraki-Asl ◽  
Paria Amiri ◽  
Habib Tvassoli ◽  
...  

Introduction: Atrophic vaginitis is a common problem in postmenopausal women and results from decreased levels of blood estrogen. It is associated with symptoms of itching, burning, dyspareunia, and postmenopausal bleeding. The present study evaluated the effects of fenugreek extract on atrophic vaginitis. Materials and Methods: This randomized controlled clinical trial was performed on 60 postmenopausal women in Ardabil, Iran, in 2018. The participants were selected using block randomization with the allocation ratio 1:1. Those in the intervention group received 0.5g (the applicator filled to the half-full mark) fenugreek vaginal cream 5% twice a week for 12 weeks. The control group received conjugated estrogens vaginal cream at the dose of 0.625 mg (the applicator filled to the half-full mark) containing 0.3 mg of conjugated estrogens. Atrophic vaginitis was evaluated before and after the treatment through clinical examination, clinical signs, and measurement of Vaginal Maturation Index (VMI). Findings: After the 12-week intervention and modification of the baseline score, the mean (standard error) score for atrophic vaginitis signs was 3.100 (1.43-4.75). This difference was statistically significant in intragroup comparison and in favor of the control group in intergroup comparison (p=0.001). VMI was less than 49% in 86.7% and 46.7% of the participants in the intervention and control groups, respectively. This was a significant difference in favor of the control group (p=0.001). Conclusion: The results of this study showed that total fenugreek extract could be effective in treating signs of atrophic vaginitis, but it was not as effective as ultra-low-dose estrogen.


2016 ◽  
Vol 44 (6) ◽  
pp. 243
Author(s):  
Ariyanto Harsono

Background Evidence begin to accumulate that high-dose sub-lingual immunotherapy (SLIT) is as effective as subcutaneousimmunotherapy (SIT) in the treatment of childhood asthma.Since the capacity of sublingual area is similar whether the doseis high or low, the efficacy of low dose may be important to bestudied.Objective To investigate the efficacy of low-dose sublingual im-munotherapy in the treatment of childhood asthma.Methods Parents signed informed consent prior to enrollment,after having received information about the study. Patients weremoderate asthma aged 6-14 years with disease onset of lessthan 2 years before the commencement of the study and peakexpiratory flow rate (PEFR) variability of more than 15%. Pa-tients were randomly allocated into group A, B, and C whoreceived subcutaneous immunotherapy, low-dose sublingualimmunotherapy, and conventional asthma therapy, respectively.Randomization was stratified into two strata according to agei.e., 6-11 years or 11-14 years. Patients of each stratum wererandomized in block of three for each group. At the end of threemonths, lung function tests were repeated. The primary outcomewas PEFR variability at the end of the study. The study wasapproved by the Ethics Committee of Soetomo HospitalSurabaya.Results Distribution of variants as represented by sex, age,eosinophil count, and total IgE concentration were normal inthe three groups. PEFR variability decreased significantly from16.97+0.81 to 8.50+5.08 and 17.0+0.87 to 8.40+4.72 in groupreceiving SIT and SLIT, respectively (p<0.05), but decreasednot significantly from 17.00+0.83 to 10.82+0.5.41 in control group(p>0.05).Conclusion Low-dose SLIT is as efficacious as SIT in the treat-ment of moderate asthma in children


2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
VV Ryabov ◽  
D Vorobyeva ◽  
YUG Lugacheva ◽  
IV Kulagina

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The reported study was funded by RFBR, project number №19-315-90106 Aim To compare indicators of blood prothrombotic activity in patients with myocardial infarction with and without coronary arteries obstruction Material and methods. The study included 40 patients with AMI (19 patients in the main group and 21 patients in the control group). Three patients (15.7%) with acute myocarditis were excluded from the analysis. Hemostasiological and hematological blood tests were studied upon admission, on the 2nd, 4th, 7th days from hospitalization. Blood samples for protein C, antithrombin, von Willebrand factor (WF), plasminogen, homocysteine were performed on 4th ± 1 day from hospitalization. To determine the IgG / IgM antibodies to cardiolipin and β2-glycoprotein for the diagnosis of APS, the ORGENTEC Anti-β2-Glycoprotein I IgG / IgM ELISA enzyme immunoassay was used. Blood tests for lupus anticoagulant were performed using an ACL-Top 700 analyzer (Werfen) with HemosIL SynthASil dRVVT screen reagents / dRVVT confirm  and with a SCT screen / SCT confirm quartz activator. Results In patients with MINOCA a statistically higher level of homocysteine (p = 0.03) and a lower level of plasminogen (p = 0.007) are determined. Protein C, antithrombin, WF the presence of lupus anticoagulant, antibodies to cardiolipin and β2-glycoprotein no differences between the groups were detected, p &gt;0.05. MINOCA patients have a statistically higher platelet level on the 2nd and 4th day of AMI (p = 0.046 and p = 0.01 ) however the level of hemoglobin and hematocrit was statistically lower on the 4th day of AMI, (p = 0.008). In the main group, a moderate correlation was found between protein C and antithrombin (r = 0.65, p = 0.0001), antithrombin and von Willebrand factor (r = 0.54, p = 0.0001), between protein C and platelet level by 4th day (r = - 0.49, p = 0.04). In MINOCA patients a moderate negative correlation was found between homocysteine and plasminogen (r = -0.69, p = 0.002). In the control group, a high correlation was found between protein C and antithrombin (r = 0.96, p = 0.0001), a moderate correlation between protein C and plasminogen (r = 0.47, p = 0.03). In addition, a relationship was revealed between the presence of thrombosis according to ICAG data and the level of ejection fraction (r = 0.46, p = 0.04) in the control group, as well as between the presence of thrombosis and the level of fibrinogen upon admission (r = 0.55, p = 0.008). Conclusions Patients with MINOCA have a higher level of homocysteine and a lower level of plasminogen. For such indicators as protein C, antithrombin III, WF the presence of antibodies on the APS is not defined differences between groups. According to laboratory data patients with MINOCA showed higher levels of platelets but lower levels of hemoglobin and hematocrit in the early post-infarction period.


Author(s):  
Akinleye Stephen Akinrinde ◽  
Halimot Olawalarami Hameed

Abstract Objectives This study examined the possible protective roles of exogenous glycine (Gly) and L-Arginine (l-Arg) against Diclofenac (DIC)-induced gastro-duodenal damage in rats. Methods Rats were divided into Group A (control), Group B (DIC group) and Groups C–F which were pre-treated for five days with Gly1 (250 mg/kg), Gly2 (500 mg/kg), l-Arg1 (200 mg/kg) and l-Arg2 (400 mg/kg), respectively, before co-treatment with DIC for another three days. Hematological, biochemical and histopathological analyses were then carried out. Results DIC produced significant (p<0.05) reduction in PCV (13.82%), Hb (46.58%), RBC (30.53%), serum total protein (32.72%), albumin (28.44%) and globulin (38.01%) along with significant (p<0.05) elevation of serum MPO activity (83.30%), when compared with control. In addition, DIC increased gastric H2O2 and MDA levels by 33.93 and 48.59%, respectively, while the duodenal levels of the same parameters increased by 19.43 and 85.56%, respectively. Moreover, SOD, GPx and GST activities in the DIC group were significantly (p<0.05) reduced in the stomach (21.12, 24.35 and 51.28%, respectively) and duodenum (30.59, 16.35 and 37.90%, respectively), compared to control. Treatment with Gly and l-Arg resulted in significant amelioration of the DIC-induced alterations although l-Arg produced better amelioration of RBC (29.78%), total protein (10.12%), albumin (9.93%) and MPO (65.01%), compared to the DIC group. The protective effects of both amino acids against oxidative stress parameters and histological lesions were largely similar. Conclusions The data from this study suggest that Gly or l-Arg prevented DIC-induced gastro-duodenal toxicity and might, therefore be useful in improving the therapeutic index of DIC.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
R. Słopień ◽  
A. Słopień ◽  
A. Różycka ◽  
A. Warenik-Szymankiewicz ◽  
M. Lianeri ◽  
...  

Objective. The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women.Methods. We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17β-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction-restriction.Results. We found that the 1460T allele ofMAO-Ac.1460C>T (SNP 1137070) appeared with a significantly higher frequency in depressed female patients than in the control group (P=0.011) and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (P=0.0198). Patients with the 1460TT genotype had a significantly higher 17β-estradiol concentration than patients with the 1460CT genotype (P=0.0065) and 1460CC genotype (P=0.0018).Conclusions. We concluded that depression in postmenopausal women is closely related to the genetic contribution ofMAO-A.


2011 ◽  
Vol 39 (01) ◽  
pp. 135-144 ◽  
Author(s):  
Guowei Zhang ◽  
Xing Zeng ◽  
Caixia Li ◽  
Jijun Li ◽  
Yu Huang ◽  
...  

The study aimed to evaluate inhibition effect of sclerotia of Polyporus umbellatus Fries aqueous extract (SPUE) and polyporus polysaccharide (PPS) on bladder cancer, then to measure their effect on mRNA expression of glutathione S-transferase π (GSTPi) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in female Fischer-344 rats model. The model rats were induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for a period of 8 weeks and saccharin for 12 weeks. SPUE (50 mg/kg, 250 mg/kg, 500 mg/kg) and PPS (28 mg/kg) were orally administrated to the model rats during the whole study. Compared to the control group, a more preventive effect of SPUE and PPS treatment on bladder cancer was discovered, higher mRNA upregulation of GSTpi and NQO1 was seen in the treatment group. Furthermore, the GSTPi and NQO1 mRNA upregulated level in the low-dose group (SPUE 50 mg/kg) was at maximum. In brief, SPUE and PPS are highly effective in inhibiting bladder carcinogenesis in rats, which may be associated with upregulation of GSTPi and NQO1 in the bladder.


2015 ◽  
Vol 21 (31) ◽  
pp. 33-36
Author(s):  
Джиоев ◽  
Inal Dzhioev ◽  
Джанаев ◽  
Robert Dzhanaev

Anthracycline antibiotic doxorubicin, which has proven cardiovascular toxicity, is often used in the treatment of cancer. The research project was carried out in 21 sexually mature Wistar male rats divided into three groups: control group, high-dose experimental group, in which rats were once injected intraperitoneally with doxorubicin hydrochloride at a dose of 10 mg/kg and low-dose experimental group, in which animals twice received intraperitoneal 2.5 mg/kg doses of doxorubicinhydrochloride at 10-day interval.An increase of malondialdehyde was revealed in the membranes of red blood cells in the high-dose experimental group, while in the low-dose experimental group a reduction in the levels of malondialdehyde and plasma hydroperoxides as well as a decreasing of catalase activity was observed. Intake of doxorubicin also causes venous hyperemia in wide areas of myocardiumalong with increasing of cardiomyocytic cross striation.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhenqiang You ◽  
Junying Sun ◽  
Feng Xie ◽  
Zhiqin Chen ◽  
Sheng Zhang ◽  
...  

Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and yeasts. In this study, we investigated the protective effects of FPEs on mammary gland hyperplasia induced by estrogen and progestogen. Rats were randomly divided into 6 groups, including a control group, an FPE-alone group, a model group, and three FPE treatment groups (each receiving 30, 15, or 5 ml/kg FPEs). Severe mammary gland hyperplasia was induced upon estradiol benzoate and progestin administration. FPEs could improve the pathological features of the animal model and reduce estrogen levels in the serum. Analysis of oxidant indices revealed that FPEs could increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, decrease malondialdehyde (MDA) level in the mammary glands and serum of the animal models, and decrease the proportion of cells positive for the oxidative DNA damage marker 8-oxo-dG in the mammary glands. Additionally, estradiol benzoate and progestin altered the levels of serum biochemical compounds such as aspartate transaminase (AST), total bilirubin (TBIL), and alanine transaminase (ALT), as well as hepatic oxidant indices such as SOD, GSH-Px, MDA, and 8-oxo-2′-deoxyguanosine (8-oxo-dG). These indices reverted to normal levels upon oral administration of a high dose of FPEs. Taken together, our results indicate that FPEs can protect the mammary glands and other visceral organs from oxidative damage.


2011 ◽  
Vol 14 (2) ◽  
pp. 66-68
Author(s):  
Natalya Alexandrovna Gavrilova ◽  
Olga Evgen'evna Tishchenko

Aim. To study effect of sulodexide (Vessel Due F) on the functional state of endothelium in patients with diabetic retinopathy. Materials and methods. A total of 37 patients with DR were divided in 2 groups and treated with sulodexide. Group 1 comprised 16 patients withnon-proliferative DR, group 2 included 21 patients with preproliferative DR. The functional state of endothelium was estimated from the plasma andserum levels of endothelial factors (sVCAM, endothelin, nitric oxide, t-PA, Willebrand factor). Results. The measurement of the initial levels of endothelial factors in both groups revealed significant changes in endothelin, nitric oxide, and sVCAMsuggesting disturbances of endothelial function due to DR. Sulodexide therapy normalized it regardless of DR stage and thereby improved functionalactivity of retina. Conclusion. This study has demonstrated beneficial effect of sulodexide on endothelial function in patients with DR due to correction of the productionof vasoactive factors (endothelin, nitric oxide) and stimulation of fibrinolytic activity of the vascular wall (t-PA).


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