0000000000011774
AUTHOR
M. A. Martínez-cuesta
Evaluation of the acute toxicity, analgesic and CNS activities of different species ofTeucrium genus
Methanol and dichloromethanol extracts of the leaves and stems of four Teucrium species (T. cartaginenses, T. flavum, T. pumillum and T. buxifolium) have been tested for their toxicity, analgesic and central depressor effects. The intraperitoneal administration of the different extracts showed a CNS depressant activity in mice, but they lacked anticonvulsive effects. When tested for analgesic activity none of the extracts increased the threshold of pain thermal stimulus. However, the methanol and dichloromethanol extracts of T. cartaginenses and T. buxifolium species showed a significant analgesic effect in models of pain induced by chemical or mechanical stimulation.
Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor
The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels—inexistent in physiological conditions—are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-…
Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95
The potential cardiovascular (CV) toxicity associated with combined antiretroviral therapy (cART) has been attributed mainly to the nucleoside reverse transcriptase inhibitors abacavir and didanosine. However, the other two components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)--may also be implicated, either directly or by influencing the action of the other drugs. This study evaluates the acute direct effects of the NNRTIs efavirenz and nevirapine and one of the most widely employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV disease.Drugs were analysed in vitro in human cells (interactions of peripheral blood…
Nitric oxide-mediated beta 2-adrenoceptor relaxation is impaired in mesenteric veins from portal-hypertensive rats.
Abstract BACKGROUND & AIMS: beta-Adrenergic relaxation seems to be mediated by nitric oxide. The aim of this study was to evaluate changes induced by portal hypertension in beta 2-adrenergic vasorelaxation. METHODS: Isolated rat mesenteric veins were relaxed by salbutamol, and nerve- mediated vasocontractions were induced by electrical field stimulation. Responses were evaluated in the presence of NG-nitro-L-arginine methyl ester (L-NAME) or tetrodotoxin. Immunocytochemical techniques were used for localization of neuronal NO synthase. RESULTS: Salbutamol-induced relaxations were decreased in rings from portal-hypertensive animals. L- NAME reduced these relaxations, but its effects were mor…
Antiinflammatory activity and effects on isolated smooth muscle of extracts from differentTeucrium species
The present study analyses the antiinflammatory effects and the action on in vitro motility of methanol and dichloromethanol extracts and stems of four Teucrium species (T. flavum, T. cartaginenses, T. buxifolium and T. pumillum). The antiinflammatory activity was tested in the carrageenan-induced paw oedema in rats. T. flavum methanol (200 mg/kg, i.p.) and dichloromethanol (138 mg/kg, i.p.) extracts showed a significant anti-inflammatory effect through the 24 h experimental period and reduced the Emax induced by histamine and serotonin in vitro on guinea-pig ileum and rat uterus respectively. These extracts did not modify the contractile effects induced by acetylcholine on rat duodenum and…
Abacavir Induces Arterial Thrombosis in a Murine Model.
Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombu…
The analgesic-antiinflammatory extract fromAraujia sericifera lacks ulcerogenic activity on stress-gastric damage model
The present study evaluates the ulcerogenic activity of the hexane extract from dry fruits of Araujia sericifera in an experimental model of cold-restraint stress. Treatment of rats with 200 mg/kg (i.p.) of hexane extract did not affect the gastric lesions induced by cold-restraint stress. However, it was confirmed that a dose of 300 mg/kg (i.p.) of acetylsalicylic acid (ASA) which induced a similar analgesic-antiinflammatory effect, increased significantly the level of gastric damage. Thus, the hexane extract from the fruits of A. sericifera seems to possess analgesic-antiinflammatory properties which are not linked to gastrolesive effects.
Abacavir induces platelet-endothelium interactions by interfering with purinergic signalling: A step from inflammation to thrombosis.
The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway. The effects of ABC on platelet aggregation and platelet-endothelium interactions were evaluated, respectively, with an aggregometer and a flo…
Involvement of prostaglandins and 5-hydroxytryptamine in the contractile effect of platelet-activating factor in rat isolated gastric corpus
Abstract The present study characterizes the nature of the response to the platelet-activating factor (PAF) in isolated gastric corpus with and without mucosa. PAF (10-8 M) induced contraction of rat isolated gastric corpus strips followed by desensitization of this tissue. Incubation of strips with the specific PAF-receptor antagonist WEB 2086 (5 × 10-8 − 5 × 10-5 M), the prostaglandin blocker indomethacin (10-6 M) and the 5-hydroxytryptamine antagonist methysergide (10-5 M) reduced significantly the contraction induced by PAF. Neither of the histamine H1/H2 antagonists diphenhydramine (10-6 M) or cimetidine (10-5 M) affected the contraction induced by PAF. In contrast with the whole gastr…
Protection by Almagate of Ethanol-induced Gastric Mucosal Damage in Rats
Abstract The study was designed to analyse the protective effects of almagate on a model of gastric injury, ethanol-induced mucosal damage, in which acid plays little, if any, role. Pretreatment with almagate dose-dependently reduced the level of gastric damage induced by oral administration of 1mL 100% ethanol. Administration of 12 μmol kg−1 almagate 30 min before ethanol significantly reduced the area of mucosal damage by 65 ± 10%, and the maximum level of inhibition (74 ± 11%) was obtained with 150 μmol kg−1 almagate. Administration of higher doses of almagate (200–250 μmol kg−1) did not result in any further increase in the level of protection against ethanol-induced gastric damage. Adm…
Involvement of endogenous nitric oxide in the inhibition by endotoxin and interleukin-1 beta of gastric acid secretion.
Administration of Escherichia coli endotoxin abolished the acid secretory response induced by a bolus injection of pentagastrin in the continuously perfused stomach of the anaesthetized rat. Likewise, acid secretion stimulated by the continuous intravenous perfusion of pentagastrin was inhibited by administration of interleukin-1 beta (IL-1 beta). In both cases pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) but not dexamethasone or indomethacin substantially restored the secretory responses to pentagastrin. The actions of L-NAME were reversed by the prior administration of L-arginine but not by its enantiomer D-arginine. Even though L-NAME increased blood pressure, this does no…
Differential effects of anti-TNF-α and anti-IL-12/23 agents on human leukocyte–endothelial cell interactions
AbstractEnhanced leukocyte recruitment is an inflammatory process that occurs during early phases of the vascular dysfunction that characterises atherosclerosis. We evaluated the impact of anti-TNF-α (adalimumab, infliximab and etanercept) and anti-IL-12/23 (ustekinumab) on interactions between human leukocytes and endothelial cells in a flow chamber that reproduced in vivo conditions. Clinical concentrations of anti-TNF-α were evaluated on the leukocyte recruitment induced by a variety of endothelial (TNF-α, interleukin-1β, lymphotoxin-α and angiotensin-II) and leukocyte (PAF, IL-12 and IL-23) stimuli related to inflammation and atherosclerosis. Treatment with anti-TNF-α, even before or af…
Nitric Oxide Modulates the Acute Increase of Gastrointestinal Transit Induced by Endotoxin in Rats: a Possible Role for Tachykinins
Abstract Because of the evidence that endogenous nitric oxide (NO) plays an essential role in the physiological regulation of gastrointestinal motility we have investigated, by use of the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), the role of endogenous NO in the acute endotoxin-induced changes of gastrointestinal transit. Pre-treatment with E. coli endotoxin (100 μg kg−, i.v.) induced a significant increase in the gastrointestinal transit of a charcoal suspension in anaesthetized rats. Previous administration of the NO synthase inhibitor, l-NAME (10 mg kg−, i.v.) significantly prevented the effects of endotoxin. l-arginine (200 mg kg−, i.v.) and the substance P antag…
Hypercholesterolemic patients have higher eryptosis and erythrocyte adhesion to human endothelium independently of statin therapy
BACKGROUND Phosphatidylserine (PS) externalization out of the membrane facilitates the eryptotic erythrocytes (EE) binding to endothelial cells (EC), potentially leading to atherosclerosis. Thus, the levels of eryptosis and interactions of EE-EC in hypercholesterolemic patients, either non-medicated or medicated, compared with healthy subjects were studied. METHODS A total of 56 subjects clustered into three groups: (control (n = 20), hypercholesterolemic non-treated (HCNT) (n = 15), and statin-treated (HCT) (n = 21)) were enrolled in this cross-sectional study. Biochemical parameters were determined with validated and standard methods. PS exposure was estimated from annexin-V-binding, cell…
The Neutrophil Secretome as a Crucial Link between Inflammation and Thrombosis
Cardiovascular diseases are a leading cause of death. Blood–cell interactions and endothelial dysfunction are fundamental in thrombus formation, and so further knowledge of the pathways involved in such cellular crosstalk could lead to new therapeutical approaches. Neutrophils are secretory cells that release well-known soluble inflammatory signaling mediators and other complex cellular structures whose role is not fully understood. Studies have reported that neutrophil extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) contribute to thrombosis. The objective of this review is to study the role of EVs and NETs as key factors in the transition from inflammation to thrombo…
Pharmacological screening of the methanol and dichloromethanol extracts ofGenista patens
The pharmacological effects of the dichloromethanol and methanol extracts obtained from leaves and stems of Genista patens DC were analysed in in vitro and in vivo models. Both extracts showed low acute toxicity (LD 50 >3 g/kg), CNS depressor and antiinflammatory activity, and similar analgesic effect in models of chemical and thermal stimulation. Furthermore, the dichloromethanol extract (1-20 mg/kg) induced a pronounced dose-dependent decrease on blood pressure. On isolated organs, the dichloromethanol extract (1, 10, 100 μg/mL) shifted the concentration-effect curve to the right for ACh and reduced the E max induced by histamine without modifying responses induced by noradrenaline and se…
Analgesic and central depressor effects of the dichloromethanol extract fromSchinus molle L.
The analgesic and central depressor effects of the dichloromethanol extract of Schinus molle L. were analysed in in vivo models. This extract showed low acute toxicity, CNS depressor activity and analgesic effect. Following further fractionation, the hexane/dichloromethane (75/25) fraction showed the most interesting results. Thus, this fraction caused a total inhibition of motor activity and significantly reduced the threshold of pain to chemical stimulus. © 1997 John Wiley & Sons, Ltd.
NG-monomethyl-L-arginine and NG-nitro-L-arginine inhibit endothelium-dependent relaxations in human isolated omental arteries.
Abstract The L-arginine analogues NG-monomethyl-l-arginine (l-NMMA, 10−4 m) and NG-nitro-L-arginine methyl ester (l-NAME, 10−4 m), which specifically inhibit the synthesis of nitric oxide from l-arginine, significantly reduced acetylcholine-induced endothelium-dependent relaxations in rings of human omental arteries. The inhibitory potency of l-NMMA and l-NAME was similar. Addition of l-NMMA or l-NAME to the organ bath did not induce any significant changes in the resting tension of the tissues. The effects of l-NMMA were reversed by l-arginine (3 × 10−4 m). The l-NMMA enantiomer, d-NMMA (10−4 m), did not influence either the basal tone of the preparation or the relaxing effects of acet…