Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-1), transforming growth factor β (TGFβ) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy.</p> <p>Methods</p> <p>Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFβ and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs.</p> <p>Results</p> <p>Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFβ, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression.</p> <p>Conclusion</p> <p>These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.</p

Chemical composition, antioxidant, and antimicrobial activities of Leaves of Ajuga iva

The main objective of this research was to study the biological characteristics in terms of antioxidant and antimicrobial activities of Ajuga iva and determine the best analytical and extraction methods applicable to this specie and studied compounds. A short screening of its nutritional value in terms of chemical composition is also included. A. iva leaves were analyzed for crude protein (CP), cell wall [neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL)], minerals, fatty acids, essential oils, and phenolic compounds. Mature aerial parts of A. iva were randomly collected during the Spring season from Mograne-Zaghouan, Tunisia. Leaves of A. iva contained 13.4 ± 0.4% CP, 26.3 ± 0.35% NDF, 20.2 ± 0.42% ADF, and 5.13 ± 0.21% ADL. Mineral content (13.0 ± 0.45%) was mainly composed of potassium (4.5% g DM) and magnesium (4.25% DM). Leaves of A. iva had linolenic (26.29 ± 0.760%) and linoleic (37.66 ± 2.35%) acids as the main components of the acid profile. Thymol was found to be the most dominant (23.43%) essential oil, followed by 4-vinylguaiacol (14.27%) and linalool (13.66%). HPLC-PDA-ESI-MS/MS analysis pointed out the presence of phytoecdysteroids. Phenolic acids and flavonoids, such as glycosylated derivatives of naringenin, eriodyctiol, and apigenin, were detected in the methanol extract of A. iva leaves. Our results underline the importance of choosing proper extraction methods and solvents to extract and characterize the described compounds profile of A. iva leaves. Results also show A. iva leaves as a potential source of functional ingredients with beneficial health-promoting properties. Overall, leaves of A. iva have low biological activities (antioxidant and antimicrobial activities) with a chemical composition suitable as a feed for ruminants in rangeland pasture. It also has low-grade antibacterial or medicinal characteristics when fed to ruminants

Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation

Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Human Fibrosarcoma Targetting Integrins with Cucurbitacin B Purified from Ecballium elaterium (L.) A. Rich

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Intravenous lidocaine to prevent endothelial dysfunction after major abdominal surgery: A randomized controlled pilot trial

Background: Major abdominal surgery is associated with endothelial glycocalyx disruption. The anti-inflammatory effects of lidocaine were recently associated with endothelial barrier protection. Methods: This was a single-centre, parallel group, randomized, controlled, double blind, pilot trial. Forty adult patients scheduled for major abdominal surgery were included between December 2016 and March 2017 in the setting of a University Hospital in Brussels (Belgium); reasons for non-inclusion were planned liver resection and conditions associated to increased risk of local anesthetics systemic toxicity. Patients were randomized to receive either lidocaine by continuous intravenous administration or an equivalent volume of 0.9% saline. The primary endpoint was the postoperative syndecan-1 concentration (difference between groups). Near-infrared spectroscopy of the thenar eminence in association with the vascular occlusion test, and contemporary analysis of flow-mediated dilation of the brachial artery were the secondary outcomes, along with haemodynamic data. Blood samples and data were collected before surgery (T0), and at 1-3 h (T1) and 24 h (T2) post-surgery. Results: Syndecan-1 concentration increased significantly post-surgery (P < 0.001), but without any difference between groups. The near-infrared spectroscopy-derived and flow-mediated dilation-derived variables showed minor changes unrelated to group assignment. Compared with the placebo group, the intervention group had a significantly lower peri-operative mean arterial pressure and cardiac index, despite equally conducted goal-directed haemodynamic management. Postoperative lactate concentrations were similar between groups. Conclusions: Lidocaine failed to have any effect on endothelial function. Since in comparisons to other types of clinical situations, syndecan-1 was only slightly upregulated, endothelial dysfunction after major abdominal surgery might be overestimated. Trial registration: « ISRCTN Registry » identifier: ISRCTN63417725. Date: 15/06/2020. Retrospectively registered.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Low-dose intravenous ketamine and clonidine for poor postoperative opioid responsiveness: a double blind randomized study.

In the immediate postoperative period, some patients present with pain that responds poorly to intravenous opioids. In a double-blind randomized study, we tested the hypothesis that administering small doses of intravenous ketamine (0.125 mg/kg) combined with clonidine (0.5 microg/kg) would enhance the speed of onset and the quality of an opioid analgesic regimen in patients who initially responded poorly to opioids. We enrolled 68 patients in the study, all physical status I to III according to the American Society of Anesthesiologists classification. If the patient's numerical rating scale (NRS) score remained > or = 5 after an initial intravenous injection of 10 mg piritramide (2-mg boluses every 5 minutes) in the post-anesthesia care unit, patients were randomized to either intravenous placebo (sodium chloride 0.9%) or active substances (ketamine 0.125 mg/kg plus clonidine 0.5 microg/kg). Fifteen minutes after administration of either placebo or active agents, patients with severe pain (NRS > 4) again received intravenous opioids until NRS < 4. The primary endpoint of the study was to reduce by 20 minutes the time necessary to achieve an NRS < 4. There was no statistically significant difference between the two groups regarding the time required for patients to achieve an NRS < 4. It was concluded that in the immediate postoperative period, the acute administration of small combined doses of intravenous ketamine (0.125 mg/kg) and clonidine (0.5 mirog/kg) does not reduce the onset of an opioid-based analgesia in patients with an initial poor response to intravenous opioids.Journal ArticleRandomized Controlled Trialinfo:eu-repo/semantics/publishe

Inhibitory effect of phenolic extract from squirting cucumber (<i>Ecballium elaterium</i> (L.) A. Rich) seed oil on integrin-mediated cell adhesion, migration and angiogenesis

International audienceIntegrin targeted therapies by natural bioactive compounds have attracted attention in the field of oncology and cancer treatment. This study evaluates the potential of phenolic extract from the medicinal herb Ecballium elaterium L. seed oil (PEO) to inhibit the adhesion and migration of the highly invasive human fibrosarcoma cell line HT1080. At safe concentrations (up to 40 mg mL −1), results show that PEO dosedependently inhibits adhesion and migration of HT1080 to fibronectin (IC 50 = 18 mg mL −1) and fibrinogen (IC 50 = 12.86 mg mL −1). These observations were associated with the reduction of cell motility and migration velocity as revealed in the Boyden chamber and random motility using two-dimensional assays, respectively. Additional experiments using integrin blocking antibodies showed that PEO at the highest safe concentration (40 mg mL −1) competitively inhibited the attachment of HT1080 cell to anti-avb3 (>98%), anti-a5b1 (>86%), and to a lesser extent anti-a2 (>50%) immobilized antibodies, suggesting that avb3 and a5b1 integrins were selectively targeted by PEO. Moreover, PEO specifically targeted these integrins in human microvascular endothelial cells (HMEC-1) and dose-dependently blocked the in vitro tubulogenesis. In the CAM model, PEO inhibited the VEGF-induced neoangiogenesis confirming its antiangiogenic effect. Collectively, these results indicate that PEO holds promise for the development of natural integrin-targeted therapies against fibrosarcoma

Cucurbitacin B purified from Ecballium elaterium (L.) A. Rich from Tunisia inhibits α5β1 integrin-mediated adhesion, migration, proliferation of human glioblastoma cell line and angiogenesis

International audienceIntegrins are essential protagonists in the complex multistep process of cancer progression and are thus attractive targets for the development of anticancer agents. Cucurbitacin B, a triterpenoid purified from the leaves of Tunisian Ecballium elaterium exhibited an anticancer effect and displayed anti-integrin activity on human glioblastoma U87 cells, without being cytotoxic at concentrations up to 500nM. Here we show that cucurbitacin B affected the adhesion and migration of U87 cells to fibronectin in a dose-dependent manner with IC50 values of 86.2nM and 84.6nM, respectively. Time-lapse videomicroscopy showed that cucurbitacin B significantly reduced U87 cells motility and affected directional persistence. Cucurbitacin B also inhibited proliferation with IC50 value of 70.1nM using Crystal Violet assay. Moreover, cucurbitacin B efficiently inhibited in vitro human microvascular endothelial cells (HMEC) angiogenesis with concentration up to 10nM. Interestingly, we demonstrate for the first time that this effect was specifically mediated by α5β1 integrins. These findings reveal a novel mechanism of action for cucurbitacin B, which displays a potential interest as a specific anti-integrin drug

Safety of bone-marrow mononuclear and mesenchymal stem cells intramyocardial injections in a canine model of chronic myocardial infarction.

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Targetting alphavbeta3 and alpha5beta1 integrins with Ecballium elaterium (L.) A. Rich. seed oil

International audienceIn the present study, the effect of Ecbalium elaterium seed oil on adhesion, migration and proliferation of human brain cancer cell line (U87) was determined. Treatment of U87 cell line with the seed oil resulted in strong inhibition of their adhesion to fibrinogen (Fg), fibronectin (Fn). It also reduced their migration and proliferation in a dose-dependent manner without being cytotoxic. Concomitantly, by using Matrigel TM assays, the oil significantly inhibited angiogenesis. The anti-tumor effect of the oil is specifically mediated by avb3 and a5b1 integrins. The presence of integrin antagonists in seed oil from E. elaterium could be used for the development of anticancer drugs with targeted " multi-modal " therapies combining anti-adhesif, antiproliferative, antimetastasic and anti-angiogenic, approaches