Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽  
2005 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Brunner-La Rocca ◽  
Schindler ◽  
Schlumpf ◽  
Saller ◽  
Suter
Keyword(s):  
Endothelial Dysfunction ◽  
Blood Lipids ◽  
Ex Vivo ◽  
Hdl Cholesterol ◽  
Blood Lipid ◽  
Tibetan Medicine ◽  
Double Blind ◽  
Intraarterial Infusion ◽  
Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

The d-Enantiomer Form of Indobufen Totally Accounts for the Anti-Cyclooxygenase and Antiplatelet Activity Ex Vivo and for the Increase in Bleeding Time by Indobufen in Man

1992 ◽  
Vol 67 (02) ◽  
pp. 258-263 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
An Yan ◽  
Walter Bernini ◽  
Daniela Giannessi ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Random Sequence ◽  
Antiplatelet Agent ◽  
Antiplatelet Drug ◽  
Double Blind

SummaryIndobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean ± S.D., 58.7 ± 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 ±3% for both treatments). At 12 h inhibition was 87 ± 6% for d-indobufen and 88 ± 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs. Maximum inhibitory effect on aggregation was seen in response to collagen 1.5 pg/ml (63 ± 44% for d-indobufen and 81 ± 22% for dl-indobufen) and arachidonic acid 0.5-2 mM (78 ± 34% for d-indobufen and 88 ± 24% for dl-indobufen) at 2 h after each administration. An effect of both treatments on platelet aggregation after 12 h was present only for adrenaline 2 μM (55 ± 41% for d-indobufen and 37 ± 54% for dl-indobufen), collagen 1.5 pg/ml (69 ± 30% for d-indobufen and 51 ± 61% for dl-indobufen), arachidonic acid 0.5-2 mM (56 ± 48% for d-indobufen and 35 ± 49% for dl-indobufen). The extent of inhibition of TX production and the extent of residual platelet aggregation were never significantly different between treatments. Bleeding time prolongation was similar in the two treatment groups without showing a pronounced and long lasting effect (from 7.0 ± 2.0 min to 10.0 ± 3.0 min at 2 h and 8.0 ± 2.0 min at 12 h for d-indobufen; from 6.0 ±1.0 min to 8.5 ± 2.0 min at 2 h and 8.0 ± 1.0 min at 12 h for dl-indobufen). These results demonstrate that the biological activity of dl-indobufen as an antiplatelet agent in vivo is totally accounted for by d-indobufen.

scholarly journals Comparison of the effects of fish oil and olive oil on blood lipids and aortic atherosclerosis in Watanabe heritable hyperlipidaemic rabbits

1998 ◽  
Vol 80 (6) ◽  
pp. 565-573 ◽  
Author(s):  
Alicja Mortensen ◽  
Birgit Fischer Hansen ◽  
Jørgen Fischer Hansen ◽  
Henrik Frandsen ◽  
Elzbieta Bartnikowska ◽  
...  
Keyword(s):  
Fish Oil ◽  
Olive Oil ◽  
Blood Lipids ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Cholesterol Content ◽  
Aortic Atherosclerosis ◽  
Atherosclerosis Development ◽  
Intermediate Density

To compare the effects of fish oil and olive oil on the development of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits, 6-week-old animals were given a daily dose (1·5 ml/kg body weight) of fish oil (n 10) or olive oil (n 10) by oral administration for 16 weeks. Plasma cholesterol and triacylglycerols were measured once monthly, and their concentrations in lipoproteins, together with susceptibility of LDL to oxidation were measured in vitro at the termination of the experiment. Aortic atherosclerosis was quantified biochemically and microscopically. After 4 weeks of treatment, and throughout the study thereafter, blood lipids were significantly (P < 0·05) lower in the fish-oil group than in the olive-oil group (cholesterol: 17·0 v. 30·3 mmol/l, triacylglycerols 2·97 v. 6·25 mmol/l, at termination). In the fish-oil group cholesterol was significantly lower in intermediate-density lipoproteins (2·69 v. 6·76 mmol/l) and VLDL (3·36 v. 11·51 mmol/l). Triacylglycerol levels of intermediate-density lipoproteins and VLDL in the fish-oil group were also significantly lower when compared with the olive-oil group (0·54 v 1·36 mmol/l and 0·92 v. 2·87 mmol/l respectively). No group differences were recorded for LDL- and HDL-cholesterol or triacylglycerol levels. A significantly higher oxidation of LDL was recorded 1 h after exposure to CuSO4 in the fish-oil group when compared with the olive-oil group (0·465 v. 0·202, arbitrary units). The following indicators of atherosclerosis development were significantly lower in the fish-oil group than in the olive-oil group: the cholesterol content (mg/g tissue) in the ascending aorta (29·8 v.48·9), the intima:media value (4·81 v. 18·24) and the area of intima (0·10 v. 0·57 mm2) in the thoracic aorta. It was concluded that fish-oil treatment decreased blood lipids and the development of aortic atherosclerosis in WHHL rabbits when compared with olive-oil treatment.

Autonomous Effects of Shear Stress and Cyclic Circumferential Stretch Regarding Endothelial Dysfunction and Oxidative Stress: An Ex Vivo Arterial Model

2009 ◽  
Author(s):  
Tyler Thacher ◽  
Rafaela da Silva ◽  
Paolo Silacci ◽  
Nikos Stergiopulos
Keyword(s):  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Ex Vivo ◽  
Cyclic Stretch ◽  
Arterial Model ◽  
Individual Contributions ◽  
Independent Effects ◽  
And Oxidative Stress

Within the vasculature endothelial cells are constantly exposed to dynamic mechanical forces generated by pulsatile blood flow. Two stimuli known to modulate endothelial function are shear stress and cyclic circumferential strain. Yet, in most studies these two stimuli are simultaneously coupled in-vivo, making it very difficult to understand their individual contributions to vascular disease. Some attempts have been made to de-couple stretch and shear stress in-vitro by using different cell lines in a variety of stretch systems and flow chambers, straying from reality and making it hard to draw definitive conclusions. In this study we wish to find a compromise between the in-vivo and in-vitro work of the past by studying the independent effects of shear stress and cyclic stretch and how they contribute to endothelial dysfunction.

P2709Wnt5a contributes to human atherosclerosis via novel USP17 redox signalling

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Akoumianakis ◽  
F Sanna ◽  
N Akawi ◽  
A Chiu ◽  
L Herdman ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Hela Cells ◽  
Ex Vivo ◽  
Cardiac Computed Tomography ◽  
Plaque Burden ◽  
Vascular Effects ◽  
Nadph Oxidases ◽  
Redox Signalling ◽  
Atherosclerosis Progression

Abstract Background Wnt5a is a non-canonical Wnt ligand with potential vascular effects, but its mechanistic role in atherosclerosis progression and the underlying downstream mechanisms are poorly explored. Purpose To address the hypothesis that Wnt5a induces vascular NADPH-oxidases activity, endothelial dysfunction and detrimental downstream redox signalling which could propagate atherosclerosis in humans. Methods Study 1 included 70 patients with coronary artery disease (CAD) versus age- and sex-matched non-CAD controls. Study 2 included 1,003 CAD patients undergoing cardiac surgery; internal mammary artery (IMA) and saphenous vein (SV) segments were harvested and used for ex vivo experiments. Study 3 included 68 individuals undergoing two cardiac computed tomography scans 3–5 years apart; calcified plaque burden was assessed by coronary calcium score (CCS). Superoxide (O2·−) generation was measured by lucigenin chemiluminescence with NADPH 100μM stimulation as indicator of NADPH-oxidases activity. Activation of Rac1, a key NADPH-oxidases subunit, was evaluated by a commercially available kit. Primary vascular smooth muscle cells (VSMCs) and HeLa cells were used for in vitro experiments. Circulating Wnt5a and Sfrp5 (a Wnt5a antagonist) were measured by ELISA in fasting plasma samples. Results In Study 1, the presence of CAD was independently linked with increased circulating Wnt5a bioavailability (A), which was, in turn, associated with increased IMA NADPH-oxidases activity in Study 2 (B). Recombinant Wnt5a directly stimulated NADPH-oxidases activity (C) via Rac1 activation (not shown) in human IMA, while inducing endothelial dysfunction evidenced by impaired SV endothelium-dependent acetylcholine (Ach) vasorelaxations (D). Transcriptomic analysis in Wnt5a-treated primary VSMCs versus controls identified USP17, a deubiquitinating enzyme implicated in Rac1 activation, as the top differentially regulated hit (not shown). Indeed, Wnt5a stimulated USP17 upregulation in VSMCs which was reversed by PEGylated superoxide dismutase (peg-SOD) 300U/mL (E), suggesting a redox sensitive effect. USP17 knockdown abolished the ability of Wnt5a to induce Rac1 activation in HeLa cells (F). At a clinical level, plasma Wnt5a was a predictor of plaque progression (defined as ΔCCS≥1, G) and new onset calcification (H) in Study 3. Conclusions We demonstrate for the first time that Wnt5a is elevated in CAD and causally associated with increased vascular oxidative stress and endothelial dysfunction in humans. We further reveal USP17 to be a novel, previously undescribed, link between Wnt5a, Rac1 activation and NADPH-oxidase activity induction in humans. We finally propose that circulating Wnt5a may have a clinically relevant role in predicting atherosclerosis progression. Our findings identify Wnt5a as rational therapeutic target in vascular disease. Acknowledgement/Funding British Heart Foundation; Alexandros S Onassis Public Benefit Foundation

An Ex Vivo Study to Evaluate the Effect of Tegaserod on Platelet Activation and Aggregation

2020 ◽  
Vol 26 (1) ◽  
pp. 40-50
Author(s):  
Paul A. Gurbel ◽  
Kevin Bliden ◽  
Scott D. Barnett ◽  
Casey Witt ◽  
Heng Zou ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Serotonin Receptor ◽  
Ex Vivo ◽  
Study Drug ◽  
Percentage Change ◽  
Pharmacokinetic Parameters ◽  
Double Blind ◽  
Cardiovascular Side Effects ◽  
Significant Difference

Introduction: Tegaserod, an orally active, potent 5-hydroxytryptamine-4 serotonin receptor agonist, was previously indicated for irritable bowel syndrome but was voluntarily withdrawn due to potential cardiovascular side effects. In vitro studies suggested that tegaserod increased platelet aggregation, but these results were not reproduced or were inconclusive. We sought to assess ex vivo effects of tegaserod on platelet aggregation. Methods: In this double-blind, placebo-controlled, crossover study, we randomized a majority of healthy patients with no history of cardiovascular risk factors (n = 21) to receive tegaserod or matching placebo for 7 + 2 days followed by a 7- to 10-day washout period, and then patients were crossed over to the other study drug for the next 7 + 2 days. Unstimulated and agonist-stimulated platelet aggregation; P-selectin expression; serum thromboxane (Tx)B2 and urinary 11-dehydro (11-dh) TxB2; and tegaserod and M29.0 concentrations were serially assessed. Results: There was no significant difference in percentage change in unstimulated or adenosine diphosphate (ADP)- and ADP + serotonin-, collagen- and thrombin receptor activating peptide–induced maximum platelet aggregation and in platelet P-selectin expression in the presence of tegaserod at any time point when compared to placebo. Similarly, there was no significant difference in percentage change in serum TxB2 or urinary 11-dhTxB2 levels between placebo and tegaserod. No new or unexpected findings were observed in evaluations of safety or pharmacokinetic parameters. Conclusion: This comprehensive pharmacodynamic study, by employing established markers used in prior investigations, which have been considered by the Food and Drug Administration to indicate drug-related platelet effects, does not demonstrate any influence of tegaserod treatment on platelet function.

A Phase 2, Double-Blind, Placebo-Controlled Trial of Rituximab + Galiximab Vs Rituximab + Placebo In Advanced Follicular Non-Hodgkin's Lymphoma (NHL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 428-428 ◽  
Author(s):  
Isabelle Bence-Bruckler ◽  
David Macdonald ◽  
Patrick J Stiff ◽  
Byron McKinney ◽  
Katherine L. Ruffner ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Controlled Trial ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
Phase 2 ◽  
Phase 3 ◽  
Double Blind

Abstract Abstract 428 Background: Galiximab is a primatized chimeric monoclonal antibody directed against CD80, an immunoregulatory protein normally expressed on antigen presenting cells and T cells, as well as in B-cell NHL, Hodgkin lymphoma, multiple myeloma, and certain leukemias. Galiximab directly mediates antibody-dependent cell-mediated cytotoxicity against tumor cells in vitro. In ex vivo assays, galiximab can act on non-malignant cells to modulate immune signaling within the tumor microenvironment. Methods: Subjects with relapsed or refractory, Grade I-IIIa, follicular NHL in relapse following treatment with at least 1 chemotherapy regimen, and who were not refractory to rituximab were randomized to rituximab (375 mg/m2) plus galiximab (500 mg/m2; R+G) or rituximab plus placebo (R+P) and treated on Days 1, 8, 15, and 22. Randomization and primary efficacy analyses were stratified by age (≤60 vs >60), rituximab exposure (rituximab naïve vs non-naïve), and baseline tumor bulk (diameter of largest lesion ≤7 cm vs >7 cm). Primary endpoint of progression-free survival (PFS) was analyzed using a stratified log-rank test. Results: This study, originally planned as a Phase 3 confirmatory study, was terminated early due to changes in standard of care and converted to a Phase 2 study. Therefore, interpretation of p-values was focused on assessing the potential of these data to support subsequent Phase 2 and Phase 3 studies. At study termination, 337 subjects were randomized (175 R+G and 162 R+P) with median follow-up of 13.8 months. Demographics and disease characteristics were well balanced across the 2 treatment groups (Table 1). The addition of galiximab to rituximab reduced the hazard for disease progression or death by 26% (hazard ratio [HR] = 0.738; 95% confidence interval [CI] [0.543, 1.002]; p = 0.050) compared to the R+P group. Kaplan-Meier median PFS was 12.0 months (95% CI [9.0, 14.7]) for R+G and 9.0 months (95% CI [8.9, 10.5]) for R+P. Overall response rate was 51% for R+G vs 48% for R+P (p = 0.455) and complete response was 20% for R+G and 15% for R+P (p = 0.251). Consistency in treatment effect was seen across patient subgroups (Figure 1). A trend toward a larger PFS effect was observed in patients who were rituximab-naïve, had bulky tumor (largest lesion >7 cm), had lactate dehydrogenase (LDH) >1 × upper limit of normal, or had bone marrow involvement at study entry. There were 10 deaths in R+G vs 17 deaths in R+P; HR = 0.549 based on a stratified log-rank analysis (95% CI [0.248, 1.217]; p = 0.135). No substantial difference was observed between groups for Grade 3/4 adverse events (AEs) or serious AEs, and there were no treatment-related deaths in either group. Incidence of AEs was ≥3% higher in the R+G vs R+P group for the following: pyrexia (18% vs 11%), headache (13% vs 7%), cough (10% vs 6%), upper respiratory infection (8% vs 4%), insomnia (8% vs 4%), neutropenia (6% vs 3%), muscle spasms (5% vs <1%), and oropharyngeal pain (4% vs 1%). Anti-galiximab antibodies were not detected in 169 subjects treated with galiximab who were tested while on study. Conclusions: Galiximab in combination with rituximab demonstrated a trend toward an improved PFS compared with rituximab alone and was well tolerated in subjects with relapsed or refractory follicular NHL. Disclosure: McKinney: Biogen Idec: Employment. Ruffner:Biogen Idec: Employment. Wilson:Biogen Idec: Employment. Whiteley:Biogen Idec: Employment.

Cocaine-Induced Endothelial Dysfunction: Role of RhoA/Rho Kinase Pathway Activation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2177-2177
Author(s):  
Jaime Pereira ◽  
Claudia G Saez ◽  
Julio Pallavicini ◽  
Karla Pereira-Flores ◽  
Camila Mendoza ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Kinase Activity ◽  
Ex Vivo ◽  
Rho Kinase ◽  
Chronic Cocaine ◽  
Cocaine Users ◽  
Rock Activity

Abstract Abstract 2177 Background. Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. We have recently demonstrated that chronic cocaine use is associated with endothelial dysfunction (Sáez et al. Thromb Res 2011; 128: 18), a key event in the onset and progression of atherosclerosis. There is growing evidence that the RhoA/Rho kinase (ROCK) pathway has an important pathophysiological role in vascular endothelial dysfunction. Accordingly, we hypothesized that cocaine use induces activation of RhoA/ROCK pathway. Objectives. The main aim of this work was to investigate the activation of RhoA/ROCK pathway through ex vivo, in vivo and in vitro studies. Methods. Ex vivo studies. We studied 13 cocaine dependent individuals (aged 19–52 years mean age 37 years) who met DSM-IV criteria for cocaine dependence, seeking treatment for cocaine abuse and age, sex-matched healthy controls (aged 20–49 years, mean age 35 years). Samples were obtained at admission, within 72 hours of drug exposure. Endothelial cell damage was determined by enumerating circulating endothelial cells (CECs). Rho-kinase activity was assessed by the levels of phosphorylated to total myosin light chain phosphatase 1 (MYPT1-P/T) in circulating leukocytes. In vivo studies. Adult male Sprague-Dawley rats were randomly assigned to receive either cocaine (30mg/kg, provided by NIDA, USA) or saline intraperitoneally once daily for 21 days. The levels of aortic phosphorylated MYPT1 (phospho-MYPT1) were assessed by western blot in aorta extracts. In vitro experiments. Human umbilical vein endothelial cells (HUVECs) were cultured under standard conditions and supplemented for 5 hours with plasma from chronic cocaine users, normal plasma, cocaine (10μM) or vehicle. After media removal, HUVECs were either lysed for determination of ROCK activity or co-cultured with resting platelets and immunostained for von Willebrand factor (FVW). Platelet adhesion was evaluated by immunofluorescence microsocopy. Experiments were conducted in the presence or absence of ROCK inhibitors, Y-27632 (10 μM) or atorvastatin (10μM). Results. Cocaine users showed significantly elevated number of CECs compared to the controls (65 ± 6.6 vs 14 ± 3.4 cells/mL, p: 0.0002). In the control subjects, leukocyte mean MYPT1-P/T ratio was 2.2 ± 0.8 whereas in cocaine addicts were significantly increased (9.8 ± 2.8; p 0.015). ROCK activity was higher by 100% (p: 0.019) in the aortic wall of the cocaine-treated rats compared to sham animals. HUVECs supplemented with plasma from cocaine users showed an increase in ROCK activity by 25% (p: 0.039), released significantly higher amount of FVW (p<0.05) and adhered a larger number of platelets (22.6±5 vs 7.9±3 platelets/cell, respectively; p: 0.006) compared with control plasma. Cocaine exposure induced a dramatically higher number of platelets adhered to HUVEC than in vehicle-treated cells (220±73 vs 10.2±1.1 platelets/cell, respectively; p>0.001).ROCK inhibitors, atorvastatin and Y-27632 reduced the release of FVW by HUVECs exposed to plasma from cocaine users by 65% (p: 0.004) and strongly inhibited platelet adhesion (by 75% in plasma-treated cells and by 90% in HUVECs exposed to cocaine, p:< 0.006). Conclusions. We found an increase in Rho kinase activity in peripheral leukocytes of cocaine abusers, in the vessel wall of rats exposed to cocaine and a marked positive effect of ROCK inhibitors on the cellular injury induced by cocaine or plasma from cocaine consumers on endothelial cells. Collectively, these data suggest that activation of RhoA/ROCK pathway plays a key role in cocaine-induced endothelial dysfunction. Inhibition of ROCK may provide therapeutic benefits in a comprehensive treatment for cocaine addiction. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ubiquinol Ameliorates Endothelial Dysfunction in Subjects with Mild-to-Moderate Dyslipidemia: A Randomized Clinical Trial

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1098 ◽  
Author(s):  
Jacopo Sabbatinelli ◽  
Patrick Orlando ◽  
Roberta Galeazzi ◽  
Sonia Silvestri ◽  
Ilenia Cirilli ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Low Density Lipoprotein ◽  
Clinical Signs ◽  
Density Lipoprotein ◽  
Primary Outcome Measure ◽  
Lipid Lowering ◽  
Ldl Oxidation ◽  
Reduced Form ◽  
Double Blind

In this randomized, double-blind, single-center trial (ANZCTR number ACTRN12619000436178) we aimed to investigate changes in endothelium-dependent vasodilation induced by ubiquinol, the reduced form of coenzyme Q10 (CoQ10), in healthy subjects with moderate dyslipidemia. Fifty-one subjects with low-density lipoprotein (LDL) cholesterol levels of 130–200 mg/dL, not taking statins or other lipid lowering treatments, moderate (2.5%–6.0%) endothelial dysfunction as measured by flow-mediated dilation (FMD) of the brachial artery, and no clinical signs of cardiovascular disease were randomized to receive either ubiquinol (200 or 100 mg/day) or placebo for 8 weeks. The primary outcome measure was the effect of ubiquinol supplementation on FMD at the end of the study. Secondary outcomes included changes in FMD on week 4, changes in total and oxidized plasma CoQ10 on week 4 and week 8, and changes in serum nitrate and nitrite levels (NOx), and plasma LDL susceptibility to oxidation in vitro on week 8. Analysis of the data of the 48 participants who completed the study demonstrated a significantly increased FMD in both treated groups compared with the placebo group (200 mg/day, +1.28% ± 0.90%; 100 mg/day, +1.34% ± 1.44%; p < 0.001) and a marked increase in plasma CoQ10, either total (p < 0.001) and reduced (p < 0.001). Serum NOx increased significantly and dose-dependently in all treated subjects (p = 0.016), while LDL oxidation lag time improved significantly in those receiving 200 mg/day (p = 0.017). Ubiquinol significantly ameliorated dyslipidemia-related endothelial dysfunction. This effect was strongly related to increased nitric oxide bioavailability and was partly mediated by enhanced LDL antioxidant protection.

scholarly journals Comparison of the Anti-Adhesion Activity of Three Different Cranberry Extracts on Uropathogenic P-fimbriated Escherichia coli: A Randomized, Double-blind, Placebo Controlled, Ex Vivo, Acute Study

2015 ◽  
Vol 10 (7) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Amy Howell ◽  
Dan Souza ◽  
Marc Roller ◽  
Emilie Fromentin
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Bacterial Adhesion ◽  
Ex Vivo ◽  
Initial Step ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Acute Study ◽  
Adhesion Activity

Research suggests that cranberry ( Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo.

In vivo stimulatory effect of multi-component herbal remedy PADMA 28 on mitogen-induced proliferation of mice splenic lymphocytes and their chemokinetic activity

2013 ◽  
Vol 16 (4) ◽  
pp. 701-705
Author(s):  
P. Skopiński ◽  
D.M. Radomska-Leśniewska ◽  
I. Sokolnicka ◽  
B.J. Bałan ◽  
A.K. Siwicki ◽  
...  
Keyword(s):  
Herbal Remedy ◽  
Wide Spectrum ◽  
Tibetan Medicine ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Splenic Lymphocytes ◽  
Beneficial Effects ◽  
Padma 28

Abstract PADMA 28, a natural herbal multi-compound remedy originates from traditional Tibetan medicine and possesses a variety of beneficial effects on experimental and clinical models of inflammation and atherosclerosis, as well as angioprotecive, antioxidative and wound - healing properties. The aim of the present study was to evaluate the in vivo influence of this remedy on the in vitro mitogen- induced proliferation of murine splenic lymphocytes and their chemokinetic activity in cell culture. The study was performed on 6-8 weeks old inbred Balb/c mice. PADMA28 was administered to mice per os in daily doses 5.8 mg (calculated from the highest dose recommended for human) or 0.085 mg (dose from the range of active doses of other herbal extracts containing polyphenolic substances used previously by us in experiments with mice), for 7 days. Control groups received water. Results: No substantial differences were observed between groups of mice fed with low and high PADMA doses. In both of them, response of splenic lymphocztes to mitogen PHA (p < 0.001) and their in vitro chemokinetic activity (p < 0.001 for low dose and p < 0.01 for high dose) were highly significantly increased as compared to the controls. Conclusion: The results of our investigations suggest that PADMA 28 can stimulate cell-mediated immunity in mice and might be used for this purpose in the wide spectrum of doses.

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