0000000000136177

AUTHOR

Francisco J. Miranda

0000-0003-3663-3902

Modulatory Role of Endothelial and Nonendothelial Nitric Oxide in 5-Hydroxytryptamine-induced Contraction in Cerebral Arteries after Subarachnoid Hemorrhage

OBJECTIVE : Endothelial dysfunction is claimed to play a role in the pathogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). We have examined the effect of experimental SAH on the modulatory action of endothelial and nonendothelial nitric oxide (NO) in the contractile response of goat middle cerebral artery to 5-hydroxytryptamine (5-HT). METHODS : We compared the 5-HT-induced contractile responses of cerebral arteries from control goats and from goats with SAH that had been experimentally induced 3 days earlier by delivery of autologous arterial blood into the subarachnoid space. Contractile responses were examined by recording the isometric tension in isolated cereb…

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Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage.

The role of endothelium-related factors in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has gained interest since the discovery of endothelin-1 (ET-1). We have examined, before and after SAH, the responsiveness of the cerebrovascular bed of the goat to ET-1, the sources of Ca2+ in ET-1-induced responses, and the ability of the Ca2+ entry blocker nicardipine to counteract them. Before SAH, injection of ET-1 into the cerebral circulation increased cerebrovascular resistance, thereby producing dose-dependent reductions in cerebral blood flow (CBF), which were prevented by nicardipine. In isolated middle cerebral arteries, ET-1 induced concentration-dependent contr…

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Impairment of the modulatory role of nitric oxide on the endothelin-1-elicited contraction of cerebral arteries: a pathogenetic factor in cerebral vasospasm after subarachnoid hemorrhage?

OBJECTIVE: Nitric oxide (NO) and endothelin-1 (ET-1) are two endothelium-derived factors probably involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Our aim was twofold, i.e., to ascertain whether endothelial and nonendothelial NO modulates the contractile response of cerebral arteries to ET-1 and to analyze whether this relationship might be impaired after experimental SAH. METHODS: Rings of middle cerebral artery from goats in the control group and from goats with SAH were set up for isometric tension recordings. SAH was induced 3 days before the experiments by infusion of 10 ml of autologous arterial blood through a catheter previously inserted into t…

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Analysis of Rabbit Vascular Responses to DBI, an Ingol Derivative Isolated from Euphorbia canariensis

Abstract We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10−8 - 3 × 10−5 m) were obtained cumulatively in both arteries at resting tension and active tone (KC1, 50 mm). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca2+-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10−4 m) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10−4 m) inhibited the maximum contraction of …

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Direct and neuromodulatory effects of histamine on isolated goat cerebral arteries.

1. The effects of histamine on isolated goat middle cerebral artery were examined using two experimental approaches: recording of isometric tension and measurement of [3H]-noradrenaline efflux. 2. Cumulative addition of histamine (10(-7)-3 x 10(-2)M) and 2-pyridylethylamine (2-PEA, 10(-6)-3 x 10(-2)M) produced concentration-dependent contractile responses. Preincubation with diphenhydramine (10(-7), 10(-6)M) or cimetidine (10(-7), 10(-6)M) competitively inhibited the histamine-induced contractile response. 3. Endothelium denudation enhanced the contractile effects of histamine. 4. Transmural electrical stimulation elicited contractions which were enhanced by histamine (10(-7)M), 2-PEA (10(-…

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Mechanisms underlying the diabetes-induced hyporeactivity of the rabbit carotid artery to atrial natriuretic peptide

Abstract Atrial natriuretic peptide (ANP) plays an important role in the pathophysiology of the vascular complications in diabetes. The working hypothesis was that diabetes might modify the vascular actions of ANP in isolated rabbit carotid arteries and the mechanisms involved in these actions. ANP (10 −12 –10 −7  M) induced a relaxation of precontracted carotid arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal increased the ANP-induced relaxation. Isatin inhibited the relaxation to ANP both in arteries with and without endothelium. Carotid arteries from diabetic rabbits showed a decreased natriuretic peptide receptor…

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Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries

Abstract The effects of three Ca 2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl 2 -, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca 2+ entry blockers and the extracellular Ca 2+ dependence of the contractions was also examined. In ‘nominally’ Ca 2+ -free medium, addition of CaCl 2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca 2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca 2+ -free medium almost abolished the noradrenaline-response…

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Comparison of the anticonstrictor action of dihydropyridines (nimodipine and nicardipine) and Mg2+ in isolated human cerebral arteries.

The isometric tension recorded from ring segments of branches of human middle cerebral artery was the parameter used to study the inhibition of spasmogen-induced contractions as model for cerebral vasospasm. Concentration-response curves to 5-hydroxytryptamine (10(-9)-3 x 10(-5) M) and prostaglandin F2 alpha (10(-7)-3 x 10(-5) M) were inhibited in Ca(2+)-free medium and in Ca(2+)-free medium to which EGTA (1 mM) had been added, respectively. Nimodipine (10(-7), 10(-5) M), nicardipine (10(-7), 10(-5) M) and Mg2+ (magnesium sulfate 10(-4), 10(-2) M) inhibited the 5-HT-elicited contractions, and this inhibition was similar for the highest concentrations tested. In contrast, nimodipine and nica…

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Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.

Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modi…

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Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries.

Abstract The response of rabbit renal arteries to acetylcholine and its endothelial modulation in diabetes were investigated. Acetylcholine induced concentration-related endothelium-dependent relaxation of renal arteries that was significantly more potent in diabetic rabbits than in control rabbits. Pretreatment with NG-nitro- l -arginine ( l -NOArg), indomethacin, or l -NOArg plus indomethacin induced partial inhibition of acetylcholine-induced relaxation. Inhibition induced by l -NOArg plus indomethacin was significantly higher in arteries from diabetic rabbits than in arteries from control rabbits. In renal arteries depolarised with KCl 30 mM and incubated with l -NOArg plus indomethacin…

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Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

The influence of diabetes on regulatory mechanisms and specific receptors implicated in the contractile response of isolated rabbit carotid arteries to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was greater in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or N(G)-nitro-L-arginine enhanced contractions in response to endothelin-1 only in control arteries, without modifying the endothelin-1 response in diabetic arteries. Indomethacin, furegrelate (thromboxane A(2) inhibitor), or cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123; endothelin ET(A) receptor antagonist) inhibited the contractions in response to en…

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Potassium channels contribute to the increased sensitivity of the rabbit carotid artery to hydrogen sulfide in diabetes

Abstract Hydrogen sulfide (H2S) is a potential endothelium-derived hyperpolarizing factor (EDHF) and adventitium- or adipocyte-derived relaxing factor (ADRF) which vasorelaxant action is mediated by potassium channels. H2S could also play an important role in the pathophysiology of diabetic cardiovascular complications. The present study has investigated the influence of alloxan-induced diabetes on the role of potassium channels mediating the relaxant response of the rabbit carotid artery to NaHS, a donor of H2S. NaHS (10−8-3 × 10−5 M) relaxed phenylephrine-precontracted carotid arteries, with higher potency in diabetic than in control rabbits. The selective blockers of potassium channels c…

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Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N(G)-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor…

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Comparative Analysis of the Vascular Actions of Diterpenes Isolated from Euphorbia canariensis

Abstract We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate (compound 1), ingenol-3-angelate-17-benzoate (compound 2), ingenol-3-angelate-17-benzoate-20-acetate (compound 3) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11-dien-14-one-5,8-bis(2-methylbutyrate)-7-(2-methylpropionate) (compound 4), four diterpenes isolated from E. canariensis, on the isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to these compounds were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension a concentration-dependent contraction was induced by the four compounds. In the basilar …

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Changes in the adrenergic mechanisms of cerebral arteries after subarachnoid hemorrhage in goats.

We have examined the effects of experimental subarachnoid hemorrhage (SAH), induced by delivering autologous blood into the subarachnoid space, on the adrenergic mechanisms of the goat cerebrovascular bed. To achieve this, the response to noradrenaline was recorded both in vivo, by measuring cerebral blood flow in unanesthetized animals, and in vitro, by recording isometric tension in isolated cerebral arteries. In addition, we checked the function of adrenergic innervation by measuring the tritium efflux evoked by electrical stimulation in cerebral arteries preloaded with [3H]-noradrenaline, and we examined this innervation by using both fluorescent and electron transmission microscopy. Al…

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Mechanisms involved in the increased sensitivity of the rabbit basilar artery to atrial natriuretic peptide in diabetes.

Atrial natriuretic peptide (ANP) is a vasodilator with significant regional differences and controversial effects in the cerebral circulation, a vascular bed particularly prone to diabetes-induced complications. The present study has investigated how alloxan-induced diabetes modifies the mechanisms involved in the response of the rabbit basilar artery to ANP. ANP (10(-12) -10(-7) M) relaxed precontracted basilar arteries, with higher potency in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal reduced ANP-induced relaxations. Inhibition of NO-synthesis attenuated ANP-induced relaxation but this attenuation was lower in diabetic than in control ra…

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Modulatory action of acetylcholine on cerebrovascular sympathetic neurotransmission

1. Acetylcholine (10 micrograms/min) diminished the electrically-induced cerebral blood flow reductions. Atropine (1-2 mg) partially blocked this inhibitory effect. 2. Exogenously administered noradrenaline (1-10 micrograms) and tyramine (50-500 micrograms) reduced cerebral blood flow but this effect was unchanged by acetylcholine infusion. 3. Acetylcholine inhibited the nonadrenergic component of the electrically-induced contraction at a concentration greater than or equal to 10(-6) M and potentiated the adrenergic component at a concentration greater than or equal to 10(5) M. Atropine 10(-7) M) inhibited both of these effects. In addition, acetylcholine (10(-4) M) enhanced the electricall…

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Influence of experimental diabetes on regulatory mechanisms of vascular response of rabbit carotid artery to acetylcholine

Summary The purpose of this study was to analyse the influence of experimental diabetes on vascular response of rabbit carotid artery to acetylcholine (Ach). We compared the Ach-induced relaxant response of isolated arterial segments obtained from both control and diabetic animals. To assess the influence of the endothelium, this cell layer was mechanically removed in some of the arterial segments (“rubbed arteries”) from each experimental group. Ach induced a concentration-related endothelium-mediated relaxation of carotid artery from control rabbits that was significantly higher with respect to that obtained in diabetic animals. Pre-treatment with NG-nitro-L-arginine (L-NA) induced a conc…

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Arthroscopic Reinsertion of Acute Injuries of the Scapholunate Ligament Technique and Results

Abstract Objective To describe a technique for treating acute injuries of the scapholunate ligament (SLL) by performing an arthroscopic reinsertion of the SLL and dorsal capsulodesis and to present the results obtained. Methods The study deals with an analytical, prospective clinical study that included 19 consecutive patients with acute injury of the SLL. The range of joint motion, grip strength, pain according to the visual analog scale, functional outcomes according to the Mayo Wrist Score (MWS), and the QuickDASH Score were studied preoperatively and 6 and 12 months postoperatively. The complications and necessary reinterventions were recorded. Results Nineteen patients with acute injur…

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Characterization of 5-Hydroxytryptamine receptors in goat cerebral arteries

1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10(-8)-3 x 10(-5) M) elicited concentration-dependent contractions with EC50 = 2.1 (1.9-2.5) x 10(-7) M and Emax = 64 +/- 2% of 50 mM KCl-induced contraction. 2. Several 5-HT receptor agonists were used: (a) the agonist of 5-HT2 receptors alpha-methyl-5-hydroxy-tryptamine (10(-7)-3 x 10(-4) M) induced strong contraction (51 +/- 6%); (b) the selective agonists of 5-HT1 receptors sumatriptan (10(-8)-10(-5) M) and 5-carboxamidotryptamine (10(-9)-10(-4) M) and the agonist of 5-HT1A receptors 8-hydroxy-2-(di-n-propylamino)tetralin (10(-7)-3 x 10(-5) M) induced weak contractions (8, 18 and 14%, respectively); and (c) …

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Evaluación funcional de los pacientes con rotura del ligamento cruzado anterior. Estudio analítico transversal

Resumen Objetivo Evaluar, mediante un analisis biomecanico, la alteracion funcional de la marcha y del equilibrio de pacientes con rotura del ligamento cruzado anterior (LCA). Material y metodo Estudio analitico transversal en 64 sujetos, 27 sujetos sanos y 37 pacientes con lesion de LCA. A todos los sujetos se les realizo un analisis biomecanico de la marcha mediante 4 pruebas: 1) prueba cinematica de la marcha, para caracterizar el patron de marcha; 2) prueba de analisis cinetico de la marcha, para analizar las caracteristicas de las fuerzas ejercidas contra el suelo, la duracion de las pisadas, la simetria entre ambas extremidades y la repetitividad del gesto analizado; 3) prueba de la m…

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Experimental diabetes induces hyperreactivity of rabbit renal artery to 5-hydroxytryptamine.

Abstract The influence of diabetes on the response of isolated rabbit renal arteries to 5-hydroxytryptamine (5-HT) was examined. 5-HT induced a concentration-related contraction that was higher in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal did not significantly modify 5-HT contractions in arteries from control rabbits but enhanced the response to 5-HT in arteries from diabetic rabbits. Incubation with N G -nitro- l -arginine ( l -NA) enhanced contractions to 5-HT in arteries from control and diabetic rabbits. In arteries with endothelium, this l -NA enhancement was lower in diabetic rabbits than in control rabbits. In arteries without endotheli…

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Utilización del ácido tranexámico tópico en la artroplastia total primaria de cadera. Eficacia y seguridad. Nuestra experiencia

Resumen Antecedentes y objetivo El acido tranexamico por via intravenosa ha demostrado que disminuye el sangrado y la necesidad de transfusiones en la artroplastia total de cadera, aunque tiene un riesgo teorico de producir fenomenos tromboembolicos. Recientemente, se han publicado algunos trabajos con la aplicacion del acido tranexamico topico, sin haberse definido todavia cual es el protocolo de administracion ideal. El objetivo de este trabajo fue demostrar que nuestro protocolo de administracion topica de acido tranexamico es eficaz y seguro. Materiales y metodos Recogida de datos de una serie prospectiva de 80 artroplastias primarias de cadera, en las que se utilizo un protocolo de aci…

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Impairment of PGC-1 Alpha Up-Regulation Enhances Nitrosative Stress in the Liver during Acute Pancreatitis in Obese Mice

Acute pancreatitis is an inflammatory process of the pancreatic tissue that often leads to distant organ dysfunction. Although liver injury is uncommon in acute pancreatitis, obesity is a risk factor for the development of hepatic complications. The aim of this work was to evaluate the role of PGC-1&alpha

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Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke

Abstract Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after…

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Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery.

Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals…

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Soy-derived phytoestrogens as preventive and acute neuroprotectors in experimental ischemic stroke: Influence of rat strain

The ability of a soy-based high-phytoestrogen diet (nutritional intervention) or genistein (pharmacological intervention), to limit ischemic brain damage in Wistar, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, has been assessed. As to the nutritional intervention, two groups from each strain received either a phytoestrogen-free (PE-0) or a high-phytoestrogen (PE-600) diet from weaning to adulthood. As to the pharmacological intervention, all animals were fed the standard soy-free AIN-93G diet and subsequently separated into two groups from each strain to receive either pure genistein (aglycone form, 1mg/kg/day intraperitoneal) or vehicle at 30 min reperfusion. After an epis…

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Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide

The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabet…

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Effects of endothelin-1 on the cerebrovascular bed of the goat.

Abstract The aim of the present study was to analyze the effects of endothelin-1 (ET-1) in the cerebrovascular bed of the goat, the importance of endothelial integrity and the contribution of extracellular Ca2+ to these responses. We measured isometric tension and 45Ca2+ uptake in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. ET-1 elicited concentration-dependent contractions which were potentiated in arteries without endothelium. Ca2+-free medium and nicardipine inhibited, and Bay K 8644 potentiated the ET-1-induced contractions. ET-1 enhanced 45Ca2+ uptake in isolated arteries. Injections of ET-1 directly into the cerebral circulation decrease…

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Diabetes-induced changes in endothelial mechanisms implicated in rabbit carotid arterial response to 5-hydroxytryptamine

Abstract The influence of diabetes on endothelial mechanisms implicated in the response of isolated rabbit carotid arteries to 5-hydroxytryptamine (5- HT ) was studied. 5-HT induced a concentration–dependent contraction that was potentiated in arteries from diabetic rabbits with respect to that in arteries from control rabbits. Endothelium removal potentiated 5-HT contractions in arteries from both control and diabetic rabbits but increased the maximum effect only in arteries from diabetic rabbits. Incubation of arterial segments with N G -nitro- l -arginine ( l- NA) enhanced the contractile response to 5-HT. This l -NA enhancement was greater in arteries from diabetic rabbits than in arter…

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Ca2+ entry blockers inhibit prostaglandin F2 alpha-induced cerebrovascular contractile responses in goats.

We examined the effects of extracellular Ca2+ withdrawal and of Ca2+ entry blockers on goat cerebrovascular responses to prostaglandin F2 alpha (PGF2 alpha). We measured isometric tension in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. PGF2 alpha produced concentration-dependent contractions of isolated arteries. The contractions were partially inhibited by incubation in Ca(2+)-free medium (by 63.1 +/- 1.8% without ethyleneglycol-bis-(beta-amino-ethylether)-N,N,N',N'-tetra-a cetate (EGTA), and by 82.4 +/- 3.7% with EGTA). The Ca2+ entry blockers inhibited PGF2 alpha-elicited contraction and relaxed PGF2 alpha-precontracted arteries (nicardipine…

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Contribution of endothelin receptors and cyclooxygenase-derivatives to the altered response of the rabbit renal artery to endothelin-1 in diabetes

Abstract The influence of diabetes on regulatory mechanisms and specific receptors implicated in the response of isolated rabbit renal artery to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was less potent in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or NG-nitro- l -arginine (L-NOARG) enhanced contractions to endothelin-1 either in control and diabetic arteries. Indomethacin inhibited endothelin-1-induced response in control arteries, but enhanced it in diabetic arteries. In contrast to that observed in rubbed and in L-NOARG treated arteries, in the presence of indomethacin the contractile action o…

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Use of topical tranexamic acid in primary total hip arthroplasty. Efficiency and safety. Our experience.

Abstract Background and aim Intravenous tranexamic acid has been shown to reduce bleeding and the need for transfusions in total hip arthroplasty, although it has a theoretical risk of producing thromboembolic phenomena. Recently some papers have been published using the topical application of tranexamic acid, but the ideal administration protocol has not yet been clearly defined. The aim of this paper was to demonstrate that our protocol of topical tranexamic acid is effective and safe. Methods Prospective data collection from a case series of 80 primary hip arthroplasties, in which the following topical tranexamic acid protocol is used: 1.5 g diluted to a total volume of 60 ml were admini…

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Functional evaluation of patients with anterior cruciate ligament injury. A transversal analytical study.

Abstract Objective To evaluate, by means of biomechanical analysis, functional alterations of gait and balance of patients with anterior cruciate ligament (ACL) injury. Material and methods Transversal analytical study on 64 people, 27 health subjects and 37 patients with ACL injury. Biomechanical analysis of gait in all individuals was performed by means of four tests: (1) kinematic test, to characterize gait pattern; (2) kinetic test, to characterize forces against the floor, duration of treads, symmetry of both legs, and the reproducibility of the gait; (3) pivot-shift test, to analyze the rotational stability of the knee on the sagittal axis; and (4) equilibrium test. Results Alteration…

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Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: A link to autonomic dysfunction in Parkinson's disease

Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein…

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Role of NO-synthases and cyclooxygenases in the hyperreactivity of male rabbit carotid artery to testosterone under experimental diabetes.

Abstract Cardiovascular disease is the major cause of morbidity and mortality in diabetic patients, which in turn is also associated with low levels of serum testosterone. The working hypothesis was that diabetes might modify the mechanisms involved in the vascular actions of testosterone in isolated rabbit carotid arteries. Testosterone (10 −8 –3 × 10 −4  M) induced a concentration-dependent relaxation of precontracted carotid arteries, which was higher in diabetic than in control rabbits. In control rabbits neither endothelium removal nor the nitric oxide synthase (NOS) inhibitor N G -nitro- l -arginine ( l -NOArg, 10 −5  M) modified the relaxant action of testosterone, and the cyclooxyge…

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Endothelial modulation of 5-hydroxytryptamine-induced contraction in goat cerebral arteries.

Abstract 1. 1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10 −8 −3 × 10 −5 M) caused concentration-dependent contractions, with EC 50 = 2.1 (1.9−2.5) × 10 −7 M and E max = 60 ± 2% of 50 mM KCl-induced contraction. 2. 2. Mechanical removal of endothelium significantly increased the E max (91 ± 8%) and did not change the EC 50 value of 5-HT-elicited contractions. 3. 3. Incubation of unrubbed arteries with the irreversible inhibitor of EDRF, gossypol (10 −5 M), significantly increased the contractile response to 5-HT ( E max = 77 ± 4%). 4. 4. Incubation of unrubbed arteries with the competitive inhibitor of the NO synthesis, N G -nitro - l -arginine (L-NOARG) …

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The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat

While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17β-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) w…

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Comparison of the contractile effects of endothelin-1 and sarafotoxin S6b in goat isolated cerebral arteries

1. The effects of endothelium-derived endothelin-1 and snake venom-derived sarafotoxin S6b, peptides with striking structural and functional similarities, were examined and compared in isolated middle cerebral arteries of goats. 2. Endothelin-1 and sarafotoxin S6b contracted cerebral arteries in a concentration-dependent manner. The potency of endothelin-1 (EC50 = 4.9 (3.9-6.2) x 10(-10) M) was about ten times higher than that of sarafotoxin S6b (EC50 = 5.5 (4.4-6.9) x 10(-9) M). The tension returned to basal values after repeated washings and contraction with endothelin-1 could be reproduced. Endothelin-1 and sarafotoxin S6b induced further contraction in arteries precontracted with prosta…

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Orthopedic versus surgical treatment of Gartland type II supracondylar humerus fracture in children.

The choice of orthopedic or surgical treatment for Gartland type II supracondylar humeral fractures remains controversial. The aim of this study was to retrospectively compare the outcomes in orthopedic and surgical treatment in type II supracondylar humeral fractures in children treated in the Orthopedic and Traumatology Children Unit of our tertiary hospital over the period between 2007 and 2010. This study suggests that orthopedic treatment is a valid option for the treatment of this type of fractures, with radiological and functional results as good as those obtained with surgical treatment, avoiding surgical complications and decreasing the hospital stay.

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Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: A comparative study with 17β-estradiol

As the knowledge on the estrogenic system in the brain grows, the possibilities to modulate it in order to afford further neuroprotection in brain damaging disorders so do it. We have previously demonstrated the ability of the selective estrogen receptor modulator, bazedoxifene (BZA), to reduce experimental ischemic brain damage. The present study has been designed to gain insight into the molecular mechanisms involved in such a neuroprotective action by investigating: 1) stroke-induced apoptotic cell death; 2) expression of estrogen receptors (ER) ERα, ERβ and the G-protein coupled estrogen receptor (GPER); and 3) modulation of MAPK/ ERK1/2 and PI3K/Akt signaling pathways. For comparison, …

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