Sodium valproate reverses aortic hypercontractility in acute myocardial infarction in rabbits.

Sympathetic nervous system (SNS), endothelin 1 (ET-1) and angiotensin II (Ang II) are involved in the pathophysiology of acute myocardial infarction (AMI). Valproic acid (VPA) is under study for the treatment against AMI due to its beneficial cardiac effects. However, the vascular effects of VPA on the activation of the SNS, ET-1 and Ang II after AMI are not fully studied.

Breaking New Ground towards Innovative Synthesis of Palladacycles: The Electrochemical Synthesis of a Tetranuclear Thiosemicarbazone-[,,] Palladium(II) Complex.

The electrochemical oxidation of anodic metals (M = nickel and palladium) in an acetonitrile solution of the thiosemicarbazone ligands ()-2-(1-(4-methoxyphenyl)ethylidene)-N-methylhydrazine-1-carbothioamide (a), ()-2-(1-(p-tolyl)ethylidene)hydrazine-1-carbothioamide (b), and ()-N-phenyl-2-(1-(p-tolyl)ethylidene)hydrazine-1-carbothioamide (c) yielded the homoleptic complexes [ML], , , , and and [ML], as air-stable solids. The crystal structures for , , , and show the ligands in a transoid disposition with the [S,S] and [N,N] donor atom pairs occupying positions on the nearly square planar coordination plane of the metal. The structure for of S4 symmetry comprises a tetranuclear palladacycle where the metalated ligands are arranged around a central PdS environment: a crown ring with alternating palladium and sulfur atoms.

Effect of mono- and dinuclear thiosemicarbazone platinacycles in the proliferation of a colorectal carcinoma cell line.

Herein, we describe the synthesis and characterization of a series of thiosemicarbazone platinacycles. Their activity towards HCT116 and A2780 cancer cell lines as well as normal fibroblasts was explored and conclusions about the influence of their structures were drawn based on the results. Ligands L1-3, tetranuclear compounds L1-3, L1-3, and L1-L3, and phosphine derivatives, were deemed unpromising owing to their lack of activity.

Levamisole Impairs Vascular Function by Blocking α-Adrenergic Receptors and Reducing NO Bioavailability in Rabbit Renal Artery.

Levamisole is an anthelmintic drug restricted to veterinary use but is currently detected as the most widely used cocaine cutting agent in European countries. Levamisole-adulterated cocaine has been linked to acute kidney injury, marked by a decrease in glomerular filtration rate, which involves reduced renal blood flow, but data on the alteration of renovascular response produced by levamisole are scarce. Renal arteries were isolated from healthy rabbits and used for isometric tension recording in organ baths and protein analysis.

Reactivity of Schiff base-[C,N,S] pincer palladacycles: hydrolysis renders singular trinuclear, tetranuclear, and heteropentanuclear PdW coordinated complexes.

Treatment of the Schiff base ligands a-f with Li[PdCl]/NaAcO in methanol under reflux gave the single nuclear palladacycles 1a-1f, with the metal atom bonded to a terdentate monoanionic [C,N,S] iminic ligand and to a chloride ligand that completes the palladium coordination sphere. Reaction of 1a-1c with silver perchlorate/triphenylphosphine in acetone at room temperature yielded the single nuclear complexes 2a-2c as the perchlorate salts, after substitution of the chloride ligand by a triphenylphosphine. However, reaction of a-c with Na[PdCl]/NaAcO in methanol at room temperature also gave compounds 1a-1c albeit contaminated with small amounts of the corresponding free aldehyde (mixture A).

Sodium valproate treatment reverses endothelial dysfunction in aorta from rabbits with acute myocardial infarction.

Sodium valproate (VPA), a histone deacetylase (HDAC) inhibitor, could be a promising candidate to treat acute myocardial infarction (AMI). In this study, AMI was induced in New Zealand White rabbits by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. The animals were distributed into three experimental groups: the sham-operated group (SHAM), the AMI group and the AMI + VPA group (AMI treated with VPA 500 mg/kg/day).

Improvement of Vascular Insulin Sensitivity by Ranolazine.

Ranolazine (RN) is a drug used in the treatment of chronic coronary ischemia. Different clinical trials have shown that RN behaves as an anti-diabetic drug by lowering blood glucose and glycosylated hemoglobin (HbA1c) levels. However, RN has not been shown to improve insulin (IN) sensitivity.

An Innovative Structural Rearrangement in Imine Palladacycle Metaloligand Chemistry: From Single-Nuclear to Double-Nuclear Pseudo-Pentacoordinated Complexes.

Treatment of the double nuclear complex , di-μ-cloro-bis[N-(4-formylbenzylidene)cyclohexylaminato-C6, N]dipalladium, with PhPCHCH)PPh (triphos) and NHPF gave the single nuclear species , 1-N-(cyclohexylamine)-4-N-(formyl)palladium(triphos)(hexafluorophasphate). Reaction of with PhPCHCHNH in refluxing chloroform via a condensation reaction of the amine and formyl groups to produce the C=N double bond, gave , 1-N-(cyclohexylamine)-4- N-(diphenylphosphinoethylamine)palladium(triphos)(hexafluorophasphate); a potentially bidentate [,] metaloligand. However, attempts to coordinate a second metal by treatment of 3a with [PdCl(PhCN)] were to no avail.

Cerium dioxide nanoparticles modulate antioxidant defences and change vascular response in the human saphenous vein.

Nanoparticles have a promising future in biomedical applications and knowing whether they affect ex vivo vascular reactivity is a necessary step before their use in patients. In this study, we have evaluated the vascular effect of cerium dioxide nanoparticles (CeONPs) on the human saphenous vein in response to relaxing and contractile agonists. In addition, we have measured the protein expression of key enzymes related to vascular homeostasis and oxidative stress.

Cyclometallated Platinum(II) Complexes with Small Crown Ether Rings: Appropriate Choice of the Bridging Diphosphane to Coordinate Potassium Cations.

This account reports the synthesis and structural characterization of the first cyclometallated platinum(II) complex that coordinates a potassium cation in a sandwich arrangement via two 15-crown-5 ether rings within the same molecule. The cooperation of the two small crown ether moieties allows the entrapment of the non-ideal potassium ion. The reaction of the parent thiosemicarbazone ligand 3,4-(CHO)CHC(Me)=NN-(H)C(=S)NHMe, , containing the crown ether ring, with K[PtCl], or alternatively with PtCl(DMSO), and subsequent treatment with the diphosphanes PhPCHPPh (dppm) and PhPC(=CH)PPh (vdpp) produced the double nuclear platinacycles , , and , probably via formation of the and intermediates.

Cyclometallated Palladium(II) Complexes: An Approach to the First Dinuclear Bis(iminophosphorane)phosphane-[C,N,S] Metallacycle.

Treatment of bis(iminophosphorane)phosphane ligands - with LiPdCl gave a set of novel diphosphane-derived complexes bearing two metallacycle rings, each one enclosing a P=N double bond: the unprecedented bis(iminophosphorane)phosphane-[C,N,S] palladacycles. In the case of the ligand derived from bis(diphenylphosphino)methane, , both the single and the double palladacycle complexes were obtained. Reaction of with bis(diphenylphosphino)ethane did not yield the expected product with the diphosphane bonded to both palladium atoms, but rather the novel coordination compound .

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture.

Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels; however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture.

Deleterious effects of levamisole, a cocaine adulterant, in rabbit aorta.

Levamisole, a veterinary anthelmintic drug, is one of the most widely used and dangerous cocaine adulterants. Like cocaine, levamisole acutely blocks noradrenaline reuptake but with much less potency, although its vascular effects are not well known. In this study, we evaluated the vascular effects of levamisole and cocaine in rabbit aortic rings used for isometric recording of tension in organ baths and protein expression by western blot.

PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits.

Background And Aims: Underlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another.

Methods: In this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis.

Results: MetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia.

Ischemia-reperfusion injury to coronary arteries: Comprehensive microscopic study after reperfused myocardial infarction.

Background: Coronary arteries supply oxygen and nutrients to the heart. We evaluated the dynamics of microscopic damage throughout the ischemia-reperfusion process in the wall of coronary arteries following myocardial infarction (MI).

Methods: In a swine model of reperfused MI, animals were divided into one control and four MI groups: 90-min ischemia without reperfusion, or followed by one minute, one week or one month reperfusion.

EpCAM and microvascular obstruction in patients with STEMI: a cardiac magnetic resonance study.

Introduction And Objectives: Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in epithelium adhesion, is an understudied area in the MVO setting. We aimed to determine whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI.

Overexpression of genes involved in lymphocyte activation and regulation are associated with reduced CRM-derived cardiac remodelling after STEMI.

Aims: Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest.

Methods: Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months.

In Vitro and In Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis.

Palladacycles are versatile organometallic compounds that show potential for therapeutic use. Here are described the synthesis and characterization of mono- and dinuclear palladacycles bearing diphosphines. Their biological effect was investigated in A2780, an ovarian-derived cancer line, and in normal dermal fibroblasts.

Chemistry of Tetradentate [,,] Iminophosphorane Palladacycles: Preparation, Reactivity and Theoretical Calculations.

A theoretical and experimental study of tetradentate [C,N : C,N] iminophosphorane palladacycles was carried out for the purpose of elucidating their behavior as compared to the parent Schiff base analogues to determine the prospect of encountering new A-frame structures for the iminophosphorane derivatives. The DFT calculations were in agreement with the experimental results regarding the performance of these ligands. New insights into the chemistry of the related dinuclear species have been obtained.

Role of antiangiogenic VEGF-Ab in angiogenesis and systolic function after reperfused myocardial infarction.

Introduction And Objectives: Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-Ab after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion.

Methods: Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction.

Action of low doses of Aspirin in Inflammation and Oxidative Stress induced by aβ on Astrocytes in primary culture.

Aspirin has been used as anti-inflammatory and anti-aggregate for decades but the precise mechanism(s) of action after the presence of the toxic peptide Aβ in cultured astrocytes remains poorly resolved. Here we use low-doses of aspirin (10 M) in astrocytes in primary culture in presence or absence of Aβ toxic peptide. We noted an increase of cell viability and proliferation with or without Aβ peptide presence in aspirin treated cells.

Relaxant and antiadrenergic effects of ranolazine in human saphenous vein.

Objectives: Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein.

Methods: Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths.