Anti-Obesity Effects Evaluation of a Blackcurrant Leaf Standardized Hydro-Alcoholic Extract in Wistar Rat Subjected to a High-Fat Diet.

Blackcurrant (BC) extract was reported to exert anti-obesity effects. However, it is unknown whether BC extract with a composition close to the totum differentially affects obesity when compared to one of its active compounds. We evaluated the anti-obesity effects of a BC standardized hydro-alcoholic leaf extract (BC-HLE) in an HFD-induced obesity rat model and compared them with quercetin (QUE).

Preventive effects of a nutraceutical mixture of berberine, citrus and apple extracts on metabolic disturbances in Zucker fatty rats.

Background: The prevention of obesity represents a major health and socio-economic challenge. Nutraceuticals are regularly highlighted for their beneficial effects in preventing the metabolic disturbances associated with obesity. However, few studies have described the combined action of nutraceutical mixtures combining polyphenols with alkaloids.

Effects of chronic mirabegron treatment on metabolic and cardiovascular parameters as well as on atherosclerotic lesions of WHHL rabbits with high-fructose high-fat diet-induced insulin resistance.

Background And Aim: Metabolic syndrome (MetS) is a global health and economic burden. Finding a suitable pharmacological approach for managing this syndrome is crucial. We explored the therapeutic potential of mirabegron (MIR), a β-adrenergic receptor agonist, as a repurposed agent for the treatment of MetS and its cardiovascular consequences.

Soluble guanylate cyclase chronic stimulation effects on cardiovascular reactivity in cafeteria diet-induced rat model of metabolic syndrome.

Metabolic syndrome is linked to an increased risk of cardiovascular complications by a mechanism involving mainly decreased nitric oxide (NO) bioavailability and impaired NO-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) signalling (NO-sGC-cGMP). To further develop this scientific point, this study aimed to investigate the effects of long-term treatment with BAY 41-2272 (a sGC stimulator) on cardiovascular reactivity of spontaneously hypertensive rats (SHR) as a model of metabolic syndrome. SHR were randomly divided into 3 groups: control group, cafeteria diet (CD)-fed group and CD-fed group treated daily with BAY 41-2272 (5 mg/kg) by gastric gavage for 12 weeks.

Sildenafil citrate long-term treatment effects on cardiovascular reactivity in a SHR experimental model of metabolic syndrome.

Much evidence indicates that metabolic syndrome is strongly correlated with a decrease in nitric oxide and an increase in oxidative stress leading to cardiovascular alterations. In recent years, gut microbiota has emerged as a new contributor to the metabolic syndrome establishment and associated cardiovascular diseases, but the underlying mechanisms remain unclear. We hypothesized that a positive modulation of cyclic guanosine monophosphate (cGMP) pathway, through phosphodiesterase type 5 (PDE5) inhibition could prevent cardiovascular alterations and gut dysbiosis that may be associated to metabolic syndrome.

Plasma homocysteine concentration in privately owned healthy adult cats: assessment of biological determinants and establishment of a reference interval.

Objectives: The assessment of homocysteine status in diseased cats has indicated high plasma concentrations in chronic kidney disease and yielded conflicting results with respect to cardiovascular disorders. Previous investigations in small populations of normal cats revealed greater-than-expected variability in plasma homocysteine concentration. The purpose of this study was to determine biological determinants and the reference interval (RI) of plasma homocysteine concentration in the feline species, under strict pre-analytical conditions.

Long-term atorvastatin treatment decreases heart maximal oxygen consumption and its vulnerability to in vitro oxidative stress in Watanabe heritable hyperlipidemic rabbit.

Statins are currently used in prevention of cardiovascular diseases in high-risk populations, and could be considered in primary prevention. However, few studies are available on the long-term effects of low doses of statins, especially on mitochondrial function and reactive oxygen species (ROS) metabolism at cardiac level. This study aimed to determine potential effects of a long-term atorvastatin treatment, at low-dose concentration, on the myocardium mitochondrial respiration.

Venous Valvular Distribution in the Thoracic and Pelvic Limbs of the Horse.

Dysfunction of venous valves can lead to hemodynamic disorders causing venous stasis, which would favour the occurrence of equine laminitis. However, very few studies have investigated venous valves in the horse digit. The purpose of this study was to compare valvular density between thoracic and pelvic limbs and to study the relationship between valvular density of veins and their location, diameter and wall thickness.

Effect of nebivolol treatment during pregnancy on the intrauterine fetal growth, mortality and pup postnatal development in the l-NAME-induced hypertensive rats.

The present study was carried out to evaluate the effect of nebivolol vs. bisoprolol treatment on the intrauterine fetal growth, mortality and postnatal development in N-Nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Hypertension was induced in normotensive pregnant Wistar rats by daily administration of l-NAME (100mg/kg/day, in the drinking water) for the period of pregnancy.

Effects of long-term active immunization with the second extracellular loop of human β- or β-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats.

Objective: To evaluate whether active immunization producing β- or β-antibodies (β-ABs and β-ABs) detected in sera of patients with dilated cardiomyopathies has deleterious effects on vascular reactivity in Lewis rat thoracic aorta (TA) and small mesenteric arteries (SMA).

Design And Method: Lewis rats were immunized for 6months with peptidic sequences corresponding to the second extracellular loop of β- and β-adrenoceptors (ARs). During the immunization, systolic blood pressure (SBP) was monitored using the tail cuff method.

Cardiac effects of long-term active immunization with the second extracellular loop of human β1- and/or β3-adrenoceptors in Lewis rats.

β1- and β3-adrenoceptor (AR) auto-antibodies were detected in patients with dilated cardiomyopathy. Many studies have shown that β1-AR auto-antibodies with partial agonist-like effect play an important role in the pathogenesis of this disease. Moreover, a recent study carried out in our laboratory has shown that β3-AR antibodies (β3-ABs), produced in rats, were able to reduce cardiomyocyte contractility via β3-AR activation.

Maximizing recombinant human serum albumin production in a Mut(s) Pichia pastoris strain.

Human serum albumin (HSA) is a cysteine rich molecule that is most abundant in human blood plasma. To remain viable in the market due to lower marketing costs for HSA, it is important to produce a large quantity in an economical manner by recombinant technology. The objective of this study was to maximize recombinant HSA (rHSA) production using a Mut(s) Pichia pastoris strain by fermentation process optimization.

Equine digital veins are more sensitive to superoxide anions than digital arteries.

This work was designed to investigate (i) the effect of superoxide dismutase (SOD) inhibition on endothelial function and (ii) the free radical-induced endothelial dysfunction in equine digital veins (EDVs) and equine digital arteries (EDAs) isolated from healthy horses. EDV and EDA rings were suspended in a 5 ml organ bath containing Krebs solution. After a 60 min equilibration period, EDV and EDA rings were contracted with phenylephrine.

[Cardiovascular effects of beta1 and beta3-adrenergic receptor autoantibodies in Lewis rat].

Purpose: To analyze vascular reactivity changes in response to immunization protocols with antigens corresponding to the second extracellular loop of -β3 and -β1 and 3 adrenergic receptors (AR).

Methods: Lewis rats were immunized for 3months with peptidic sequences corresponding to the second extracellular loop of β3-AR or β1 and 3-AR. Specific β3-AR antibodies were characterized by Elisa and purified using "Proteus Protein G" kit.

Antibodies against the second extracellular loop of β₁-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat.

Autoantibodies against β₁-adrenoceptors (β₁-ARs) have been detected in the serum of patients with various cardiac diseases; however, the pathological impact of these autoantibodies (β₁-AABs) has only been evaluated in cardiac tissue. The purpose of the present study was to evaluate whether β₁-AABs have deleterious effects on vascular reactivity in rats. An enzyme-linked immunosorbent assay was used to detect β₁-AABs in sera from immunized rats over a period of 1-3 months using the peptidic sequence of the second extracellular loop of human β₁-AR.

Celiprolol induces β(3)-adrenoceptors-dependent relaxation in isolated porcine coronary arteries.

In porcine coronary arteries (PCAs), celiprolol, a selective β(1)-adrenoceptors antagonist, induces vasodilatation by an endothelium- and nitric oxide (NO)-dependent pathway. However, the mechanisms of that vascular effect have not been precisely established. β(3)-Adrenoceptors have been shown to be involved in the relaxation per se of various vascular beds, including coronary vessels.

Vasorelaxant effect of propentofylline in isolated equine digital veins.

We evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental conditions. PPF-induced relaxation was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (an adenosine receptor antagonist; 3 µM).

Binding of DC-SIGN to glycoproteins expressed in glycoengineered Pichia pastoris.

Previous studies have shown that glycoproteins expressed in wild-type Pichia pastoris bind to Dendritic cell-SIGN (DC-Specific Intercellular adhesion molecule-3 Grabbing Nonintegrin), a mannose-binding receptor found on dendritic cells in peripheral tissues which is involved in antigen presentation and the initiation of an immune response. However, the binding of DC-SIGN to glycoproteins purified from P. pastoris strains engineered to express humanized N- and O-linked glycans has not been tested to date.

[Antibodies against the second extracellular loop of beta1-adrenergic receptor induce aortic endothelial dysfunction in Wistar rat].

Purpose: To evaluate the effect of active immunization with a peptide corresponding to the second extracellular loop of the human beta1-adrenoceptors (β(1)-AR) on the reactivity of Wistar rat isolated aorta.

Methods: Nine-week-old Wistar rats were actively immunized for 3months with a peptide corresponding to the second extracellular loop of the human β(1)-AR. Specific immunoglobulins G (IgG) were characterized by Elisa and the bicinchonic acid protein assay and their functionality were tested in isolated ventricular cardiomyocytes (IVC) from control rats.

Autoantibodies against cardiac β(1)-adrenoceptor do not affect the low-affinity state β(1)-adrenoceptor-mediated inotropy in rat cardiomyocytes.

Circulating autoantibodies directed against the 2nd extracellular loop (EL-2) of β(1)-adrenoceptors (β(1)-AABs) have been detected in the serum of patients with various cardiovascular pathologies. β(1)-AABs induce agonistic, positive inotropic effects via β(1)-adrenoceptors (β(1)ARs). In the mammalian heart, β(1)-AR can exist in 2 distinct activated configurations (the so-called high- and low-affinity states).

Optimization of erythropoietin production with controlled glycosylation-PEGylated erythropoietin produced in glycoengineered Pichia pastoris.

Pichia pastoris is a methylotropic yeast that has gained great importance as an organism for protein expression in recent years. Here, we report the expression of recombinant human erythropoietin (rhEPO) in glycoengineered P. pastoris.

Vasodilatory effect of pentoxifylline in isolated equine digital veins.

The direct vasodilatory action of pentoxifylline (1-(5-oxohexyl)-3,7-dimethylxanthine) and its signalling pathway was evaluated in equine digital veins. Cumulative concentration-response curves to pentoxifylline (1 nM to 300 μM) were recorded in phenylephrine-precontracted equine digital vein rings under different experimental conditions. Relaxation to pentoxifylline was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (a non-xanthine adenosine receptor antagonist; 3 μM).

Improved production of monoclonal antibodies through oxygen-limited cultivation of glycoengineered yeast.

Glycoengineering technology can elucidate and exploit glycan related structure-function relationships for therapeutic proteins. Glycoengineered yeast has been established as a safe, robust, scalable, and economically viable expression platform. It has been found that specific productivity of antibodies in glycoengineered Pichia pastoris is a non-linear function of specific growth rate that is dictated by a limited methanol feed rate.

Glycoengineered Pichia produced anti-HER2 is comparable to trastuzumab in preclinical study.

Mammalian cell culture systems are used predominantly for the production of therapeutic monoclonal antibody (mAb) products. A number of alternative platforms, such as Pichia engineered with a humanized N-linked glycosylation pathway, have recently been developed for the production of mAbs. The glycosylation profiles of mAbs produced in glycoengineered Pichia are similar to those of mAbs produced in mammalian systems.