RESUMEN
Videolaryngoscopes are thought to improve glottic view and facilitate tracheal intubation compared with the Macintosh direct laryngoscope. However, we currently do not know which one would be the best choice in most patients undergoing anaesthesia. We designed this systematic review with network meta-analyses to rank the different videolaryngoscopes and the Macintosh direct laryngoscope. We conducted searches in PubMed and a further five databases on 11 January 2021. We included randomised clinical trials with patients aged ≥16 years, comparing different videolaryngoscopes, or videolaryngoscopes with the Macintosh direct laryngoscope for the outcomes: failed intubation; failed first intubation attempt; failed intubation within two attempts; difficult intubation; percentage of glottic opening seen; difficult laryngoscopy; and time needed for intubation. We assessed the quality of evidence according to GRADE recommendations and included 179 studies in the meta-analyses. The C-MAC and C-MAC D-Blade were top ranked for avoiding failed intubation, but we did not find statistically significant differences between any two distinct videolaryngoscopes for this outcome. Further, the C-MAC D-Blade performed significantly better than the C-MAC Macintosh blade for difficult laryngoscopy. We found statistically significant differences between the laryngoscopes for time to intubation, but these differences were not considered clinically relevant. The evidence was judged as of low or very low quality overall. In conclusion, different videolaryngoscopes have differential intubation performance and some may be currently preferred among the available devices. Furthermore, videolaryngoscopes and the Macintosh direct laryngoscope may be considered clinically equivalent for the time taken for tracheal intubation. However, despite the rankings from our analyses, the current available evidence is not sufficient to ensure significant superiority of one device or a small set of them over the others for our intubation-related outcomes.
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Intubación Intratraqueal/métodos , Laringoscopía/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Procedimientos y Técnicas Asistidas por Video , Adulto , Humanos , Intubación Intratraqueal/normas , Laringoscopía/normas , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto/normasRESUMEN
Hypoxia induced by low O2 pressure is responsible for several physiological and behavioral alterations. Changes in physiological systems are frequent, including inflammation and psychobiological declines such as mood and cognition worsening, resulting in increased reaction time, difficulty solving problems, reduced memory and concentration. The paper discusses the possible relationship between glutamine supplementation and worsening cognition mediated by inflammation induced by high altitude hypoxia. The paper is a narrative literature review conducted to verify the effects of glutamine supplementation on psychobiological aspects. We searched MEDLINE/PubMed and Web of Science databases and gray literature by Google Scholar for English articles. Mechanistic pathways mediated by glutamine suggest potential positive effects of its supplementation on mood and cognition, mainly its potential effect on inflammation. However, clinical studies are scarce, making any conclusions impossible. Although glutamine plays an important role and seems to mitigate inflammation, clinical studies should test this hypothesis, which will contribute to a better mood and cognition state for several people who suffer from problems mediated by hypoxia.
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Afecto/efectos de los fármacos , Altitud , Cognición/efectos de los fármacos , Glutamina/administración & dosificación , Glutamina/farmacología , Hipoxia , Suplementos Dietéticos , HumanosRESUMEN
Objetivou-se comparar as alterações cardiorrespiratórias e a analgesia pós-operatória promovidas pela dexmedetomidina e pelo tramadol, quando associados ao midazolam, em felinas. Para tal, foram selecionadas 18 gatas hígidas, divididas em dois grupos randomizados: GDM, tratadas com dexmedetomidina (10µg/kg) e GTM, tratadas com tramadol (2mg/kg), ambos associados a midazolam (0,2mg/kg,) IM. Após 15 minutos, procedeu-se à indução anestésica com propofol (1,46±0,79mL), mantendo-se a anestesia com isoflurano. As felinas foram submetidas à ovário-histerectomia, registrando-se as variáveis cardiorrespiratórias 15 minutos após a MPA (M0), 15 minutos após a indução (M15) e sequencialmente a cada cinco minutos, até o término do procedimento cirúrgico (M20, M25, M30, M35 e M40). A avaliação da dor iniciou-se 30 minutos após o término do procedimento cirúrgico (MP30) e sequencialmente em intervalos de 30 minutos (MP60, MP90, MP120). A partir do MP120, as avaliações foram registradas a cada hora (MP180, MP240 e MP360). A associação dexmedetomidina-midazolam infere diminuição inicial de frequência cardíaca (FC) sem significado clínico e está relacionada à sedação mais pronunciada, à analgesia menor e menos duradoura e a episódios de êmese, quando comparada à associação tramadol-midazolam. Ambos os protocolos denotaram estabilidade cardiorrespiratória e podem ser considerados seguros em felinas submetidas à ovário-histectomia.(AU)
The aim of this study was to compare cardiorespiratory changes and post-operative analgesia provided by dexmedetomidine or tramadol, associated with midazolam, in female cats. For that purpose, 18 healthy cats were assigned to two randomized groups: GDM, which received dexmedetomidine (10 µg/kg) and GTM, which received tramadol (2 mg/kg), both associated with midazolam (0.2 mg/kg) IM. After 15 minutes, anesthesia was induced with propofol (1.46±0.79 mL) and maintained with isofluorane. Ovariohysterectomy was performed and cardiorespiratory variables were registered 15 minutes after pre-anesthetic medication (M0), 15 minutes after anesthetic induction (M15), and every five minutes until the end of the surgical procedure (M20, M25, M30, M35 e M40). Pain evaluation started 30 minutes after the surgery (MP30) and sequentially at thirty-minute intervals (MP60, MP90, MP120). After MP120, each evaluation was registered at every hour (MP180, MP240 e MP360). Dexmedetomidine-midazolam association results in decreases on initial heart rate (HR) without clinical relevance and it is related to pronounced sedation, poor and less durable antinociception and vomiting events, when compared to tramadol-midazolam association. Both protocols indicate cardiorespiratoy stability and safety in cats undergoing ovariohysterectomy.(AU)
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Animales , Femenino , Gatos , Dexmedetomidina/análisis , Isoflurano/uso terapéutico , Midazolam/análisis , Tramadol/análisis , Anestésicos Combinados/uso terapéutico , Histerectomía/veterinaria , Ovariectomía/veterinaria , Frecuencia RespiratoriaRESUMEN
A 16-year-old female who was attended as an outpatient reported localized, acute abdominal pain with vomiting, symmetrical motor weakness, and burning sensation in both arms and legs. Her medical history showed irrational behavior, repeated admissions at the emergency units of many other reference hospitals, where she had been investigated for celiac disease and treated with analgesics for pain events. Her clinical condition remained unchanged despite the use of many oral analgesics. In those admissions, she showed dysautonomia, vomiting, and abdominal pain. Diagnosis investigation disclosed a notable serum hyponatremia (133.7 mEq/L). She was referred for endoscopy and the histopathological lesion of the antrum in the stomach did not show neoplastic lesions. Colonoscopy, pelvic magnetic resonance imaging (MRI), total abdominal computed tomography, and video laparoscopy were without significant abnormalities. Suspicion of acute intermittent porphyria was confirmed by quantitative urine porphobilinogen-level tests and genetic analysis. Patient was successfully treated with intravenous infusion of glucose and hemin therapy.
RESUMEN
BACKGROUND: and purpose: The peptide PnPP-19, derived from the spider toxin PnTx2-6 (renamed as δ-CNTX-Pn1c), potentiates erectile function by activating the nitrergic system. Since NO has been studied as an antinociceptive molecule and PnPP-19 is known to induce peripheral antinociception, we intended to evaluate whether PnPP-19 could induce peripheral antinociception through activation of this pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PGE2 (2 µg/paw) was administered intraplantarly together with PnPP-19 and inhibitors/blockers of NOS, guanylyl cyclase and KATP channels. The nitrite concentration was accessed by Griess test. The expression and phosphorylation of eNOS and nNOS were determined by western blot. KEY RESULTS: PnPP-19 (5, 10 and 20 µg/paw) induced peripheral antinociception in rats. Administration of NOS inhibitor (L-NOarg), selective nNOS inhibitor (L-NPA), guanylyl cyclase inhibitor (ODQ) and the blocker of KATP (glibenclamide) partially inhibited the antinociceptive effect of PnPP-19 (10 µg/paw). Tissue nitrite concentration increased after PnPP-19 (10 µg/paw) administration. Expression of eNOS and nNOS remained the same in all tested groups, however the phosphorylation of nNOS Ser852 (inactivation site) increased and phosphorylation of eNOS Ser1177 (activation site) decreased after PGE2 injection. Administration of PnPP-19 reverted this PGE2-induced effect. CONCLUSIONS AND IMPLICATIONS: The peripheral antinociceptive effect induced by PnPP-19 is resulting from activation of NO-cGMP-KATP pathway. Activation of eNOS and nNOS might be required for such effect. Our results suggest PnPP-19 as a new drug candidate to treat pain and reinforce the importance of nNOS and eNOS activation, as well as endogenous NO release, for induction of peripheral antinociception.
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Analgésicos/farmacología , GMP Cíclico/metabolismo , Canales KATP/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico/metabolismo , Péptidos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Pie/fisiopatología , Masculino , Óxido Nítrico Sintasa de Tipo I/análisis , Óxido Nítrico Sintasa de Tipo III/análisis , Manejo del Dolor , Sistema Nervioso Periférico/efectos de los fármacos , Fosforilación , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Venenos de ArañaRESUMEN
Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang-(1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1-7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang-(1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7)-vasorelaxant response.
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Angiotensina I/metabolismo , Arterias Carótidas/metabolismo , Regulación de la Expresión Génica , Hipertensión/metabolismo , Fragmentos de Péptidos/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina , Vasodilatación , Animales , Arterias Carótidas/patología , Arterias Carótidas/fisiopatología , Hipertensión/patología , Hipertensión/fisiopatología , Ibuprofeno/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Proto-Oncogenes Mas , Ratas , Ratas WistarRESUMEN
The aim of this study was to investigate the effects of a 6-month exercise program on cognitive function and blood viscosity in sedentary elderly men. Forty-six healthy inactive men, aged 60-75 years were randomly distributed into a control group (n=23) and an experimental group (n=23). Participants underwent blood analysis and physical and memory evaluation, before and after the 6-month program of physical exercise. The control group was instructed not to alter its everyday activities; the experimental group took part in the fitness program. The program was conducted using a cycle ergometer, 3 times per week on alternate days, with intensity and volume individualized at ventilatory threshold 1. Sessions were continuous and maximum duration was 60 min each. There was significant improvement in memory (21%; P<0.05), decreased blood viscosity (-19%; P<0.05), and higher aerobic capacity (48%; P<0.05) among participants in the experimental group compared with the control group. These data suggest that taking part in an aerobic physical fitness program at an intensity corresponding to ventilatory threshold-1 may be considered a nonmedication alternative to improve physical and cognitive function.
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Viscosidad Sanguínea , Ejercicio Físico/fisiología , Memoria/fisiología , Aptitud Física/fisiología , Conducta Sedentaria , Anciano , Umbral Anaerobio/fisiología , Estudios de Casos y Controles , Tolerancia al Ejercicio/fisiología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Consumo de Oxígeno/fisiología , Distribución Aleatoria , Factores Socioeconómicos , Factores de TiempoRESUMEN
The mullet Mugil liza occurs along the Atlantic coast of South America from Venezuela to Argentina, but 95% of the commercial catch is collected from south Brazil between São Paulo and Argentina. Mugil liza is a single spawner with oocyte development occurring synchronously in two groups. Spawning happens in marine areas and occurs after migration. The reproductive migration occurs from Argentina (38° S) to the southern Brazilian states (24-26° S) from April to July, with peak spawning in June between northern Santa Catarina and Paraná. The presence of hyaline oocytes was associated with high salinity and sea surface temperatures of 19-21° C, and followed the seasonal northward displacement of these oceanographic conditions. The average size at first maturity (Lm ) for both sexes was 408·3 mm total length, LT . Males (Lm = 400·1) matured earlier than females (Lm = 421·9 mm). Fecundity ranged from 818,992 to 2,869,767 oocytes (mean = 1,624,551) in fish that were between 426 and 660 mm LT .
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Migración Animal , Reproducción , Smegmamorpha/fisiología , Animales , Océano Atlántico , Tamaño Corporal , Brasil , Femenino , Fertilidad , Masculino , Ovario/anatomía & histología , Salinidad , Temperatura , Testículo/anatomía & histologíaRESUMEN
BACKGROUND & AIMS: Butyrate is a four-carbon fatty acid that presents anti-inflammatory, anti-oxidative and apoptotic properties in colon and several cell lines. Because atherosclerosis has important oxidative and inflammatory components, butyrate could reduce oxidation and inflammation, impairing atherogenesis. We evaluated the effects of butyrate supplementation of butyrate on atherosclerosis and its mechanisms of action. METHODS AND RESULTS: ApoE knockout mice were fed on chow diet or 1% butyrate-supplemented chow diet (Butyrate) for 10 weeks to assess atherosclerosis lesions area and inflammatory status. Macrophage and endothelial cells were also pretreated with butyrate (0.5 mM) for 2 h before oxLDL stimulation to study oxLDL uptake and pro and anti-inflammatory cytokine production. Butyrate reduced atherosclerosis in the aorta by 50%. In the aortic valve, butyrate reduced CCL2, VCAM1 and MMP2 productions in the lesion site, resulting in a lower migration of macrophage and increased collagen depositions in the lesion and plaque stability. When EA.hy926 cells were pretreated with butyrate, oxLDL uptake, CD36, VCAM1, CCL2 TNF, IL1ß and IL6 productions were reduced, whereas IL10 production was increased. These effects were accompanied by a lower activation of NFκB due to a lower nuclear translocation of the p65 subunit. CONCLUSION: Oral butyrate is able to slow the progression of atherosclerosis by reducing adhesion and migration of macrophages and increasing plaque stability. These actions are linked to the reduction of CD36 in macrophages and endothelial cells, decreased pro-inflammatory cytokines and lower activation of NFκB all of these data support a possible role for butyrate as an atheroprotective agent.
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Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/uso terapéutico , Aterosclerosis/dietoterapia , Ácido Butírico/uso terapéutico , Suplementos Dietéticos , Placa Aterosclerótica/prevención & control , Factor de Transcripción ReIA/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/metabolismo , Antioxidantes/metabolismo , Aorta/inmunología , Aorta/metabolismo , Aorta/patología , Válvula Aórtica/inmunología , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Aterosclerosis/inmunología , Aterosclerosis/metabolismo , Aterosclerosis/fisiopatología , Ácido Butírico/metabolismo , Antígenos CD36/antagonistas & inhibidores , Antígenos CD36/metabolismo , Adhesión Celular , Línea Celular , Movimiento Celular , Núcleo Celular , Células Cultivadas , Endotelio Vascular/inmunología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Humanos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/patología , Masculino , Ratones Noqueados , Placa Aterosclerótica/etiología , Transporte de Proteínas , Factor de Transcripción ReIA/metabolismoRESUMEN
BACKGROUND AND AIMS: Thiamine deficiency is a condition that is known to cause damage to the nervous and cardiovascular systems because it interferes with cellular metabolism. It is well known that the control of vascular function is highly dependent on the production of nitric oxide (NO) by NO synthases. Studies exploring the physiological relevance of NO signaling under conditions of thiamine deficiency are scarce. The present study sought to investigate whether chronic metabolic changes would cause alterations in vascular responsiveness. METHODS AND RESULTS: By removing thiamine from the diet, we observed a reduced acetylcholine-mediated relaxation and an increased phenylephrine-mediated vasoconstriction in the aortas containing functional endothelium. Removal of the endothelium or the pre-treatment of vessels with l-NAME restored the contractile responses to the level of controls. Conversely, indomethacin did not modify phenylephrine-mediated contractions. We also used carbon microsensors to continually measure NO production in situ while simultaneously measuring the vascular tone. The results revealed a significant decrease in NO production. Western blot analysis showed a decreased expression of the total eNOS in the thiamine-deficient aorta compared to the control. Concentration-response curves for phenylephrine indicated no difference between the control and deficient groups in the presence and absence of SOD or Tyron. The NO donor DEA-NONOate produced a concentration-dependent relaxation response in the endothelium-denuded vessels that did not differ between the control and thiamine-deficient rats. CONCLUSION: Thiamine deficiency modulates eNOS-dependent NO production, leading to a decreased vasorelaxation and an increased contractile response in the rat aorta.
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Óxido Nítrico/metabolismo , Deficiencia de Tiamina/patología , Enfermedades Vasculares/patología , Acetilcolina/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Hidrazinas/farmacología , Indometacina/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fenilefrina/farmacología , Ratas , Ratas Wistar , Deficiencia de Tiamina/complicaciones , Enfermedades Vasculares/etiología , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
Members of the spider genus Lasiodora are widely distributed in Brazil, where they are commonly known as caranguejeiras. Lasiodora spider venom is slightly harmful to humans. The bite of this spider causes local pain, edema and erythema. However, Lasiodora sp. spider venom may be a source of important pharmacological tools. Our research group has described previously that Lasiodora sp. venom produces bradycardia in the isolated rat heart. In the present work, we sought to evaluate the vascular effect of Lasiodora sp. venom and to isolate the vasoactive compounds from the venom. The results showed that Lasiodora spider venom induced a concentration-dependent vasodilation in rat aortic rings, which was dependent on the presence of a functional endothelium and abolished by the nitric oxide synthase (NOS) inhibitor L-NAME. Western blot experiments revealed that the venom also increased endothelial NOS function by increasing phosphorylation of the Ser¹¹77 residue. Assay-directed fractionation isolated a vasoactive fraction from Lasiodora sp. venom. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) assays identified a mixture of two compounds: adenosine diphosphate (ADP, approximately 90%) and adenosine monophosphate (AMP, approximately 10%). The vasodilator effects of Lasiodora sp. whole venom, as well as ADP, were significantly inhibited by suramin, which is a purinergic P2-receptor antagonist. Therefore, the results of the present work indicate that ADP is a main vasodilator component of Lasiodora sp. spider venom.
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Adenosina Difosfato/farmacología , Venenos de Araña/química , Arañas/química , Vasodilatadores/farmacología , Adenosina Difosfato/química , Adenosina Monofosfato/química , Animales , Western Blotting , Fraccionamiento Químico , Endotelio/efectos de los fármacos , Técnicas In Vitro , Espectrometría de Masas , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico Sintasa/metabolismo , Resonancia Magnética Nuclear Biomolecular , Fosforilación/efectos de los fármacos , Ratas , Suramina/química , Vasodilatación/efectos de los fármacos , Vasodilatadores/químicaAsunto(s)
Guarderías Infantiles , Dermatomicosis/epidemiología , Dermatomicosis/microbiología , Hongos Mitospóricos/clasificación , Hongos Mitospóricos/enzimología , Fosfolipasas/metabolismo , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Higiene , Lactante , Recién Nacido , Masculino , Pobreza , PrevalenciaRESUMEN
A pre-concentration procedure with solid-phase extraction was developed for the determination of arsenic (As) in chicken feed using hydride generation atomic absorption spectrometry (HG-AAS). The procedure was based on the sorption of As(III) ions as complexes with ammonium pyrrolidine dithiocarbamate onto a mini-column packed with polyurethane foam. After pre-concentration, the As was removed from the mini-column by acid solution, and the analyte content in the eluate was measured by HG-AAS. The following main experimental conditions were established: adjustment of the As solution pH with 0.05 mol l⻹ HCl, 2.88 × 10⻳ mol l⻹ complexing agent concentration and 6.0 mol l⻹ eluting hydrochloric acid concentration. The proposed method produced an enrichment factor of 67, with 0.050 and 0.165 µg g⻹ limits of detection and quantification, respectively. The procedure was applied to the determination of As content in two types of chicken feed using the proposed procedure and atomic absorption spectrometry with electrothermal atomisation (ETAAS). The t-test indicated that the results were not significantly different at a confidence level of 95%.
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Alimentación Animal/análisis , Arsénico/análisis , Contaminantes Ambientales/análisis , Contaminación de Alimentos , Inspección de Alimentos/métodos , Adsorción , Animales , Aniones/química , Arsénico/química , Arsénico/aislamiento & purificación , Brasil , Quelantes/química , Pollos , Contaminantes Ambientales/química , Contaminantes Ambientales/aislamiento & purificación , Hidrógeno/química , Concentración de Iones de Hidrógeno , Límite de Detección , Poliuretanos/química , Pirrolidinas/química , Reproducibilidad de los Resultados , Extracción en Fase Sólida/métodos , Espectrofotometría Atómica/métodos , Tiocarbamatos/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Hancornia speciosa Gomes are popularly used in Brazil to treat diabetes and hypertension. Cardiovascular diseases are the main cause of death worldwide and their incidences are increasing in Brazilian population. The present study aimed to investigate the hypotensive effect and the mechanism of action of Hancornia speciosa Gomes. METHODS: A fraction of the ethanolic extract of leaves from Hancornia speciosa (SFH) was obtained and standardized by its content on rutin, bornesitol and quinic acid. Systolic blood pressure (SBP) of normotensive mice was measured by tail plethysmography. SFH was given orally and SBP was monitored for 5h. Angiotensin-converting enzyme (ACE) inhibitor activity of SFH (1mg/kg) or captopril (10mg/kg) was measured by colorimetric methods. Serum nitrite levels were measured by spectrophotometry. RESULTS: SFH induced a dose-dependent hypotensive effect in normotensive mice. The serum activity of ACE and the level of angiotensin II were significantly reduced by SFH and by captopril. Administration of SFH induced a significant increase on plasmatic level of nitrites and the systemic inhibition of nitric oxide synthase by L-NAME (20mg/kg) reduced the hypotensive effect of SFH. CONCLUSIONS: The present work demonstrated that Hancornia speciosa has a potent hypotensive effect in normotensive mice. The inhibition of ACE leading to reduction on angiotensin II and increase on NO levels might account for the hypotensive effect. These results support the use of Hancornia speciosa by traditional medicine as antihypertensive.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Apocynaceae , Presión Sanguínea/efectos de los fármacos , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Administración Oral , Angiotensina II/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/química , Antihipertensivos/aislamiento & purificación , Apocynaceae/química , Captopril/farmacología , Etanol/química , Masculino , Ratones , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Nitritos/sangre , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Plantas Medicinales , Pletismografía , Solventes/química , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND AND PURPOSE: Reduced NO availability has been described as a key mechanism responsible for endothelial dysfunction in atherosclerosis. We previously reported that neuronal NOS (nNOS)-derived H(2)O(2) is an important endothelium-derived relaxant factor in the mouse aorta. The role of H(2)O(2) and nNOS in endothelial dysfunction in atherosclerosis remains undetermined. We hypothesized that a decrease in nNOS-derived H(2)O(2) contributes to the impaired vasodilatation in apolipoprotein E-deficient mice (ApoE(-/-)). EXPERIMENTAL APPROACH: Changes in isometric tension were recorded on a myograph; simultaneously, NO and H(2)O(2) were measured using carbon microsensors. Antisense oligodeoxynucleotides were used to knockdown eNOS and nNOS in vivo. Western blot and confocal microscopy were used to analyse the expression and localization of NOS isoforms. KEY RESULTS: Aortas from ApoE(-/-) mice showed impaired vasodilatation paralleled by decreased NO and H(2)O(2) production. Inhibition of nNOS with L-Arg(NO2) -L-Dbu, knockdown of nNOS and catalase, which decomposes H(2)O(2) into oxygen and water, decreased ACh-induced relaxation by half, produced a small diminution of NO production and abolished H(2)O(2) in wild-type animals, but had no effect in ApoE(-/-) mice. Confocal microscopy showed increased nNOS immunostaining in endothelial cells of ApoE(-/-) mice. However, ACh stimulation of vessels resulted in less phosphorylation on Ser852 in ApoE(-/-) mice. CONCLUSIONS AND IMPLICATIONS: Our data show that endothelial nNOS-derived H(2)O(2) production is impaired and contributes to endothelial dysfunction in ApoE(-/-) aorta. The present study provides a new mechanism for endothelial dysfunction in atherosclerosis and may represent a novel target to elaborate the therapeutic strategy for vascular atherosclerosis.
Asunto(s)
Aterosclerosis/fisiopatología , Endotelio Vascular/fisiopatología , Peróxido de Hidrógeno/metabolismo , Óxido Nítrico Sintasa de Tipo I/fisiología , Acetilcolina/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiopatología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Catalasa/farmacología , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo I/deficiencia , Óxido Nítrico Sintasa de Tipo I/genética , Óxido Nítrico Sintasa de Tipo III/deficiencia , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/fisiología , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: Vasculopathies represent the main cause of morbidity and mortality in diabetes. Vascular malfunctioning in diabetes is associated with abnormal vasoconstriction and Ca(2+) handling by smooth muscle cells (SMC). Phosphatidylinositol 3-kinases (PI3K) are key mediators of insulin action and have been shown to modulate the function of voltage-dependent L-type Ca(2+) channels (Ca(V) 1.2). In the present work, we investigated the involvement of PI3K signalling in regulating Ca(2+) current through Ca(V) 1.2 (I(Ca,L) ) and vascular dysfunction in a mouse model of type I diabetes. EXPERIMENTAL APPROACH: Changes in isometric tension were recorded on myograph. Ca(2+) currents in freshly dissociated mice aortic SMCs were measured using the whole-cell patch-clamp technique. Antisense techniques were used to knock-down the PI3Kδ isoform. KEY RESULTS Contractile responses to phenylephrine and KCl were strongly enhanced in diabetic aorta independent of a functional endothelium. The magnitude of phenylephrine-induced I(Ca,L) was also greatly augmented. PI3Kδ expression, but not PI3Kα, PI3Kß, PI3Kγ, was increased in diabetic aortas and treatment of vessels with a selective PI3Kδ inhibitor normalized I(Ca,L) and contractile response of diabetic vessels. Moreover, knock-down of PI3Kδin vivo decreased PI3Kδ expression and normalized I(Ca,L) and contractile response of diabetic vessels ex vivo. CONCLUSIONS AND IMPLICATIONS: Phosphatidylinositol 3-kinase δ was essential to the increased vascular contractile response in our model of type I diabetes. PI3Kδ signalling was up-regulated and most likely accounted for the increased I(Ca,L,) leading to increased vascular contractility. Blockade of PI3Kδ may represent a novel therapeutic approach to treat vascular dysfunction in diabetic patients.
Asunto(s)
Canales de Calcio Tipo L/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Aorta/fisiopatología , Calcio/metabolismo , Fosfatidilinositol 3-Quinasa Clase I , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Contracción Muscular , Músculo Liso Vascular/fisiopatología , Miocitos del Músculo Liso/fisiología , Técnicas de Placa-Clamp , Inhibidores de las Quinasa Fosfoinosítidos-3 , Receptores Adrenérgicos alfa 1/metabolismo , Transducción de Señal , Regulación hacia Arriba , Vasoconstricción , VasodilataciónRESUMEN
In the present work we investigated the mechanism involved in the vasodilator effect induced by euxanthone in rat small mesenteric arteries. We observed that euxanthone induced concentration-dependent vasodilatation in arteries by a mechanism independent on the release of endothelial factors, such as nitric oxide (NO) and cyclooxygenase-derived factors. In addition our results also suggest that euxanthone induced its vasodilator effect through inhibition of calcium-sensitive mechanisms activated by protein kinase C, rather than by inhibition of contractions dependent on the release of the intracellular calcium stores or by inhibition of voltage-operated calcium channels.
Asunto(s)
Calcio/metabolismo , Clusiaceae/química , Extractos Vegetales/farmacología , Proteína Quinasa C/metabolismo , Vasodilatación/fisiología , Vasodilatadores/farmacología , Xantonas/farmacología , Animales , Canales de Calcio/metabolismo , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Masculino , Arterias Mesentéricas/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
C(60)-derived nanobaskets, with chemical formulae (symmetry point group) C(40)H(10) (C(5v)), C(39)H(12) (C(3v)), C(46)H(12) (C(2v)), were investigated. Molecular dynamic simulations (MDSs) indicate that the molecules preserve their bonding frame for temperatures up to 300 K (simulation time 100 ps), and maintain atomic cohesion for at least 4 ps at temperatures up to 3500 K. The infrared spectra of the C(60)-derived nanobaskets were simulated through density functional theory (DFT) calculations, allowing for the attribution of infrared signatures specific to each carbon nanobasket. The possibility of using C(60)-derived nanobaskets as molecular containers is demonstrated by performing a DFT study of their bonding to hydrogen, water, and L-alanine. The carbon nanostructures presented here show a higher bonding energy (approximately 1.0 eV), suggesting that a family of nanostructures, C(n)-derived (n = 60,70,76,80, etc) nanobaskets, could work as molecular containers, paving the way for future developments such as tunable traps for complex molecular systems.
RESUMEN
Adsorption of ascorbic acid (AsA) on C60 is investigated using classical molecular mechanics and density functional theory (DFT). Classical annealing was performed to explore the space of molecular configurations of ascorbic acid adsorbed on C60, searching for optimal geometries. From the structure with the smallest total energy, 10 initial configurations were prepared by applying rotations of 90 degrees about three orthogonal axes. Each one of these configurations was optimized using DFT (for both LDA and GGA exchange-correlation functionals), and an estimate of their total and adsorption energies was found. Different configurations have minimal adsorption energies (defined here as the total energy of the adsorbate minus the total energy of the separate molecules) from -0.54 to -0.10 eV, with distinct optimal distances between the AsA and C60 centers of mass. According to a Hirshfeld population analysis, AsA is, in general, an acceptor of electrons from C60. Our results demonstrate the feasibility of noncovalent functionalization of C60 with AsA and provide minimal energy values for the several different configurations investigated. These results should be considered in reactions as a possible way to prevent against the oxidative damage and toxicity of C60. The beneficial effects of using AsA-C60 includes its action when administered together with levodopa, against the neurotoxicity generated by levodopa isolated, which opens new strategies for the Parkinson's disease treatment.