Aspirin and COX-2 Inhibitor Nimesulide Potentiate Adrenergic Contractions of Human Gastroepiploic Artery

Background The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine. Methods Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to electrical field stimulation, norepinephrine, and acetylcholine, in the absence and presence of COX-1 or COX-2 inhibition. Results The COX-1 and COX-2 inhibitor aspirin at high concentrations (10 −6 to 10 −5 mol/L) and the COX-2 inhibitor nimesulide (10 −6 mol/L…

Aprendiendo de forma cooperativa a través del método científico

[EN] Usually, students tend to divide tasks unequally when they have to work in groups, everyone prepares a part of the manuscript and later they bind all parts together and deliver it. In this way, learning is fragmented and the desired goal is not achieved: to work cooperatively. In our experience we proposed students to work as a group of scientists. From a brief background they had to write an introduction, design a protocol using the indicated experimental technique and finally they had to speculate and discuss on the expected results. The activity should have raised the cooperation among all group members, because the correct understanding of a section required of the understanding of…

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

Abstract 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. Our results indicated that MetS did not change the contractile response in either the aorta or renal artery. Conversely, vasodi…

Modulation of adrenergic contraction of dog pulmonary arteries by nitric oxide and prostacyclin.

Abstract The aim of this work was to investigate the influence of endothelium-derived nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. Electrical field stimulation (1–8 Hz, 20 v, 0.25 ms duration, for 30 s) produced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10−6 M). Noradrenaline induced concentration-dependent contractions with an EC50 of 1.85 × 10−6 M. The increases in tension induced by electrical stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. In segments with endothelium, NG-nitro- l …

Arginine Vasopressin Enhances Sympathetic Constriction Through the V 1 Vasopressin Receptor in Human Saphenous Vein

Background —Arginine vasopressin (AVP) not only acts directly on blood vessels through V 1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins. Methods and Results —Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3×10 −9 mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectiv…

Endothelium-dependent component in the contractile responses of human omental arteries to adrenergic stimulation

Abstract The present study was designed to investigate the influence of endothelium-derived nitric oxide on the contractile responses of isolated human omental arteries to electrical field stimulation and noradrenaline. We measured isometric tension in artery rings obtained from portions of human omentum during the course of abdominal operations (32 patients). Electrical field stimulation induced frequency-dependent contractions which were abolished by tetrodotoxin (10−6 M) and prazosin (10−6 M), thus indicating that this effect was due to noradrenaline released from adrenergic nerves acting on α1-adrenoceptors. The increases in tension induced by electrical field stimulation were of greate…

Tyrosine Phosphorylation Modulates the Vascular Responses of Mesenteric Arteries from Human Colorectal Tumors

The aim of this study was to analyze whether tyrosine phosphorylation in tumoral arteries may modulate their vascular response. To do this, mesenteric arteries supplying blood flow to colorectal tumors or to normal intestine were obtained during surgery and prepared for isometric tension recording in an organ bath. Increasing tyrosine phosphorylation with the phosphatase inhibitor, sodium orthovanadate produced arterial contraction which was lower in tumoral than in control arteries, whereas it reduced the contraction to noradrenaline in tumoral but not in control arteries and reduced the relaxation to bradykinin in control but not in tumoral arteries. Protein expression of VEGF-A and of th…

Neurogenic contraction and relaxation of human penile deep dorsal vein

The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. Electrical field stimulation (0.5–2 Hz) and noradrenaline (3×10−10–3×10−5M) caused frequency- and concentration-dependent contractions that…

Chronic exercise impairs nitric oxide pathway in rabbit carotid and femoral arteries

KEY POINTS: Some of the beneficial effects of exercise in preventing vascular related diseases are mediated by the enhancement of endothelial function where the role of nitric oxide (NO) is well documented, although the relevance of calcium activated potassium channels is not fully understood. The impact of oxidative stress induced by training on endothelial function remains to be clarified. By evaluating different endothelial vasodilator pathways on two vascular beds in a rabbit model of chronic exercise, we found a decreased NO bioavailability and endothelial nitric oxide synthase expression in both carotid and femoral arteries. Physical training induced carotid endothelial dysfunction as…

Relaxant and antiadrenergic effects of ranolazine in human saphenous vein.

Abstract 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. Concentration–response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency–response and concent…

Relaxation and cyclic GMP levels in response to sildenafil in human pulmonary arteries from donors.

We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.

Effects of aspirin, nimesulide, and SC-560 on vasopressin-induced contraction of human gastroepiploic artery and saphenous vein.

Objective: The present experiments were designed to evaluate differences in the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on contractile responses of human gastroepiploic artery and saphenous vein elicited by vasopressin. Design: Laboratory investigation. Setting: University laboratory. Subjects: Rings of human gastroepiploic artery were obtained from 32 patients undergoing gastrectomy, and rings of saphenous vein were obtained from 30 patients undergoing coronary artery bypass surgery. Interventions: The rings were suspended in organ baths for isometric recording of tension. We studied the responses to vasopressin in the absence and in the presence of either the vasopressin V …

Diseño de una rúbrica para evaluar trabajos en grupo: revisión y reflexión

[EN] Rubrics are scoring guides that, when done right, offer teachers some advantages while qualifying. Our experience consisted in elaborate a rubric to evaluate the group work and analyze the qualifications obtained, broken down by sections and compare them with weight given to each section within the rubric. The aim of our study was to analyze whether the rubric used was discriminatory, as well as, to detect strengths and weaknesses in the designed rubric. The results showed a wide range of qualifications once evaluated with our rubric. 80% of rubric featured well-defined descriptors and of the remaining 20%, 10% was evaluated by students and the other 10% was too subjective because eval…

Endothelin-1-induced potentiation of adrenergic responses in the rabbit pulmonary artery: role of thromboxane A(2).

Abstract To examine whether low concentrations of endothelin-1 potentiate the vasocontrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10 −10 M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET B receptor antagonist (2,6-dimethylpiperidinecarbonyl-γ-methyl-Leu- N in -[Methoxycarbonyl]- d -Trp- d -Nle) (BQ-788, 10 −6 M), but not the endothelin ET A receptor antagonist cyclo( d -Asp-Pro- d -Val-Leu- d -TRP) (BQ-123, 10 −6 M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibit…

Influence of Endothelial Nitric Oxide on Adrenergic Contractile Responses of Human Cerebral Arteries

The present study was designed to investigate the influence of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3–8 h before. EFS (1–8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10-6 M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-monomethyl L-arginine (L-NMMA 10-4 M) potentiated the contractile response to EFS in artery rings with endothelium but did not …

Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin

Purpose: The goal of this study was to determine the effects of vasopressin and the selective V 2 -receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses. Methods: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V,-receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 −6 mol/L), the V 1 -V 2 receptor antagonist desGly-d(CH 2 ) 5 D-T…

Role of Ca2+-Activated K+ Channels on Adrenergic Responses of Human Saphenous Vein

Background We studied the participation of K + channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca 2+ channels on modulation of adrenergic responses by K + channels blockade. Methods Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. Results Iberiotoxin (10 −7 mol/L), an inhibitor of large conductance Ca 2+ -activated K + channels, and charybdotoxin (10 −7 mol/L), an inhibitor of both large and intermediate conductance Ca 2+ -activated K + channels, enhanced the contractions elicited by elec…

Function of Glia in Aging and the Brain Diseases.

Microglia cells during aging, neurodegeneration and neuroinflammation show different morphological and transcriptional profiles (related to axonal direction and cell adhesion). Furthermore, expressions of the receptors on the surface and actin formation compared to young are also different. This review delves into the role of glia during aging and the development of the diseases. The susceptibility of different regions of the brain to disease are linked to the overstimulation of signals related to the immune system during aging, as well as the damaging impact of these cascades on the functionality of different populations of microglia present in each region of the brain. Furthermore, a decr…

Anti-adrenergic effects of ranolazine in isolated rat aorta

Ranolazine, a piperazine derivative, is used as an anti- anginal drug to treat patients with chronic angina in clinical practice [1] and may improve coronary blood flow by reducing compression effects of ischemic contracture, and by improving endothelial function [2],[3]. In the present study we investigate the vascular effects of ranolazine on the endothelium, adrenergic system and Ca2+ in isolated rat aorta.

Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery

1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10[10]-10[-7] M) caused concentration-dependent contractions (pD2 = 8.36+/-0.09). The V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10[-9]-10[-8] M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA2 value of 9.83 with a slope of 1.10+/-0.14. 3. Vasopressin (3 x 10[-10] and 10[-9] M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms dura…

Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1

One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ1-42 depositions. Our results indicate that Aβ1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated re…

Effects of exercise training on adrenergic and cholinergic responses of rabbit carotid artery

Material multimedia para aumentar el rendimiento académico de los trabajos en grupo

[EN] Multimedia can be considered a useful tool for improving the learning. In this study we analyze the marks that students get in a group activity with and without the use of a multimedia material made by teachers. The scores are obtained using a rubric previously tested for this activity and the results show an increase in the final qualification for student groups who used the multimedia material. We also analyze the scores by units following the rubric and we note that scores increase 4.0 points for a maximum of 10 in the methodology unit. Moreover, we collect the opinion of our students about the multimedia material and how it helped them to better understand the work they had to do i…

Enhancement by vasopressin of adrenergic responses in human mesenteric arteries.

Vasopressin not only acts directly on blood vessels through V1-receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vitro and in vivo. The aim of the present study was to investigate whether subpressor concentrations of vasopressin could modify the constrictor responses to norepinephrine and electrical stimulation of the perivascular nerves in human mesenteric arteries. Human mesenteric artery rings (3-3.5 mm long, 0.8-1.2 mm OD) were obtained from 38 patients undergoing abdominal operations. The arterial rings were suspended in organ bath chambers for isometric recording of tension. Vasopressin (3 x 10(-11) M) enhanced the contractions elicited…

Bifidobacterium pseudocatenulatum CECT 7765 supplementation restores altered vascular function in an experimental model of obese mice

Aims. Bifidobacterium pseudocatenulatum CECT 7765 improves metabolic and immunological altered functions in high fat fed mice, however little is known about the effects of potential probiotics on vascular reactivity. The aim of the present study was to investigate the effects of a potential probiotic strain, Bifidobacterium pseudocatenulatum CECT 7765, on vascular response in obese mice. Methods. Aorta samples were obtained from mice, which were divided into three groups: a control group, receiving a standard diet; an obese group, receiving a high-fat diet; and an obese group receiving high-fat diet and a daily dose of B. pseudocatenulatum CECT 7765 by oral gavage. Aortic rings were suspend…

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 and 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. Ins at 10-8 M, Rn (10-6 M) and Ins+Rn (10-8 M and 10−6 M respectively) were added to astrocytes during 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. p-AKT, p-ERK, p-eNOS, Mn-SOD, COX-2, and t…

Contractile responses of human thyroid arteries to vasopressin

Abstract Aims In the present study we investigated the intervention of nitric oxide and prostacyclin in the responses to vasopressin of isolated thyroid arteries obtained from multi-organ donors. Main methods Paired artery rings from glandular branches of the superior thyroid artery, one normal and the other deendothelised, were mounted in organ baths for isometric recording of tension. Concentration–response curves to vasopressin were determined in the absence and in the presence of either the vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 − 8  M), the nitric oxide synthase inhibitor N G -monomethyl- l -arginine ( L -NMMA, 10 − 4  M), or the inhibitor of prostaglandins indom…

Effects of photodynamic therapy in periodontal treatment: A randomized, controlled clinical trial

Aim To evaluate the effects of photodynamic therapy (PDT) in the nonsurgical treatment of chronic periodontitis. Materials and methods A randomized, single-blind, controlled, parallel-group clinical trial was performed. Sixty patients were enrolled: 20 healthy controls and 40 patients with periodontitis. The 40 patients were randomized for scaling and root planing (SRP) or SRP+PDT. Periodontal (plaque index, probing depth, clinical recession, clinical attachment level, bleeding on probing, and gingival crevicular fluid volume, corresponding to 381 vs 428 critical sites), microbiological (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema dentico…

Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer's Disease

The amyloid precursor protein plus presenilin-1 (APP/PS1) mice are a frequently-used model for Alzheimer's disease studies (AD). However, the data relevant to which proteins are involved in inflammatory mechanism are not sufficiently well-studied using the AD mouse model. Using behavioral studies, quantitative RT-PCR and Western-blot techniques, significant findings were determined by the expression of proteins involved in inflammation comparing APP/PS1 and Wild type mice. Increased GFAP expression could be associated with the elevation in number of reactive astrocytes. IL-3 is involved in inflammation and ABDF1 intervenes normally in the transport across cell membranes and both were found …

Effects of vasopressin on human renal arteries

The effects of vasopressin were studied in isolated rings from branches (2-3 mm in external diameter) of human renal arteries obtained from 18 patients undergoing nephrectomy for non-obstructive neoplasia. In arterial rings under resting tension, vasopressin produced concentration-dependent and endothelium-independent contractions with an EC 50 of 9.1 x 10 -10 mol L -1 . The vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 -6 mol L -1 ) displaced the control curve to vasopressin 564-fold to the right in a parallel manner. In precontracted arterial rings and previously treated with the V 1 antagonist (10 -6 mol L -1 ) vasopressin caused endothelium-independent relaxation. The re…

Role of endothelium and calcium channels in endothelin-induced contraction of human cerebral arteries

Endothelin constricted human isolated cerebral arteries in a concentration-dependent manner. The maximal tension developed, as well as EC50 values were similar in arteries with and without endothelium. Removal of extracellular calcium or addition of the calcium antagonist nicardipine (10(-6)M), attenuated but did not abolish responses to endothelin. These experiments show that the endothelin-induced contraction in human cerebral arteries is not linked to the presence of intact endothelial cells. The data also show that the contractile effects of endothelin cannot be explained solely by an action on voltage-dependent calcium channels.

Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries.

The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients). Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-nitro-L-arginine meth…

Vasopressin receptors involved in adrenergic neurotransmission in the circular muscle of the human vas deferens

We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced con…

Anti-inflammatory and antioxidant effects of ranolazine on primary cultured astrocytes

Because of its ability to block late INa [1], ranolazine is used as an antianginal agent for the treatment of chronic angina pectoris when angina is not adequately controlled by other agents [2]. Besides its cardiovascular effects, ranolazine improves different neuronal functions, and thus its use has been proposed for the treatment of pain and epileptic disorders [3,4]. Since astrocytes are involved in neuronal inflammatory processes, and autoimmune and neurodegenerative diseases [5], we have investigated the antiinflammatory and antioxidant effects of ranolazine in primary cultured astrocytes.

Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels

Abstract Background . Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. Methods . Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was…

4-Hydroxynonenal, a lipid peroxidation product, induces relaxation of human cerebral arteries.

The relaxant effect of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, on human cerebral arteries was studied. Addition of 4-HNE to artery rings promoted no contraction, and after stimulation with prostaglandin F2α (PFG2α; 10−7-3 × 10−6 M), 100% relaxation was obtained with 3 × 10−5 M 4-HNE. Inhibition of nitric oxide formation with NG-nitro-l-arginine methyl ester hydrochloride (l-NAME; (10−4 M), as well as prostaglandin synthesis with indomethacin (3 × 10−6 M), partially prevented 4-HNE-induced relaxation, but each of these substances separately failed to inhibit complete relaxation. Addition of both inhibitors together reduced 4-HNE-induced relaxation to ≈50%, but relaxation cou…

Endothelial dysfunction in morbid obesity.

Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. …

Neuronal effects of Sugammadex in combination with Rocuronium or Vecuronium.

Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these…

Inflammatory Chemokines Expression Variations and Their Receptors in APP/PS1 Mice

Background: In Alzheimer’s disease (AD), an increase in inflammation is distinctive. Amyloid precursor protein plus presenilin-1 (APP/PS1 mice) is a model for this illness. Chemokines secreted by central nervous system (CNS) cells could play multiple important roles in AD. Data looking for the chemokines involved in inflammatory mechanisms are lacking. To understand the changes that occur in the inflammation process in AD, it is necessary to improve strategies to act on specific inflammatory targets. Objective: Chemokines and their receptors involved in phagocytosis, demyelination, chemotaxis, and coagulation were the objective of our study. Methods: Female APPswe/PS1 double-transgenic mice…

Relaxation of human isolated mesenteric arteries by vasopressin and desmopressin.

1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the…

Effects of Ranolazine on Astrocytes and Neurons in Primary Culture.

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10-7, 10-6 and 10-5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The …

Contractile hyporesponsiveness to norepinephrine of forearm veins in chronic renal failure.

Background We recently reported that endothelium-dependent relaxation is impaired in forearm veins from patients with chronic renal failure. However, assessment of responses to norepinephrine remains controversial. We examined the contractile response to norepinephrine in forearm veins from patients on chronic hemodialysis and the role of nitric oxide (NO), prostanoids, and Ca 2+ -activated K + channels in this response. Methods Isometric contraction curves were obtained in rings of forearm vein from 21 dialyzed patients and 12 multiorgan donors in response to norepinephrine (1 nmol/L to 10 μmol/L) or KCl (5 to 100 mmol/L). Results Veins from uremic patients were markedly less responsive to…

The Role of Chemokines in Alzheimer's Disease

Objective: The most common multifactorial neurodegenerative disorder occurring in old age is Alzheimer’s disease. The neuropathological hallmarks of that disorder are amyloid plaques with the presence of β -amyloid aggregates, intraneuronal tau protein tangles, and chronic inflammation. Brain cells such as microglia and astrocytes are inflammatory cells associated with Alzheimer’s disease and involved in the production of inflammatory mediators, such as cytokines and chemokines. Chemokines consist of a large family of protein mediators with low molecular weight, which able to control the migration and residence of all immune cells. In pathological conditions, such as Alzheimer’s disease, c…

Action of low doses of Aspirin in Inflammation and Oxidative Stress induced by aβ1-42 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 Aβ1-42 in cultured astrocytes remains poorly resolved. Here we use low-doses of aspirin (10-7 M) in astrocytes in primary culture in presence or absence of Aβ1-42 toxic peptide. We noted an increase of cell viability and proliferation with or without Aβ1-42 peptide presence in aspirin treated cells. In addition, a decrease in apoptosis, determined by Caspase 3 activity and the expression of Cyt c and Smac/Diablo, were detected. Also, aspirin diminished necrosis process (LDH levels), pro-inflammatory mediators (IL-β and TNF-α) and NF-ᴋB prot…

WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid β1-42 effects on astrocytes in primary culture

Alzheimer's disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death. Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD. However, studies on the effects of cannabinoids on astrocytes functions are scarce. In primary cultured astrocytes we studied cellular viability using MTT assay. Inflammatory and oxidative stress mediators were determined by ELISA and Western-blot techniques both in…

Sugammadex, a Neuromuscular Blockade Reversal Agent, Causes Neuronal Apoptosis in Primary Cultures

Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system). Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we …

Increased responsiveness of human pulmonary arteries in patients with positive bronchodilator response.

Abstract 1. The effects of noradrenaline, endothelin-1, acetylcholine and sodium nitroprusside were studied in isolated pulmonary arteries obtained from 14 patients undergoing lobectomy for lung carcinoma. Seven patients had shown increased response to a bronchodilator test prior to operation. In the remaining patients (control) the bronchodilator test was negative. 2. Artery rings from patients with a positive bronchodilator response showed greater contraction to noradrenaline (pD2 = 6.44 +/- 0.1; Emax = 93 +/- 9% of response to 100 mM KCl) and endothelin-1 (pD2 = 8.92 +/- 0.1; Emax = 130 +/- 16%) than the rings from control patients (pD2 = 6.04 +/- 0.08; Emax = 56 +/- 8% for noradrenaline…

Contractile Response of Human Omental Arteries to Endothelin

Abstract The effects of endothelin have been studied in isolated arterial segments (0·8–1 mm in external diam.) of human omental arteries obtained during the course of abdominal operations (15 patients, 7 men and 8 women). Paired segments, one normal and the other de-endothelized, were mounted for isometric recording of tension in organ baths. Endothelin produced concentration-dependent contractions with an EC50 value of 5·4 × 10−9  m. Removal of endothelium did not affect significantly endothelin-induced contractions (EC50, 6·7 × 10−9  m). Removal of extracellular calcium or addition of the calcium channel blocker nicardipine (10−6  m) diminished but did not abolish responses to endothelin…

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…