RESUMEN
"BACKGROUND: Fall-related injuries among the elderly (age 65 and older) are the cause of nearly 750,000 hospitalizations and 25,000 deaths per year in the United States, yet prevention research is lagging. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, the Eastern Association for the Surgery of Trauma produced this practice management guideline to answer the following injury prevention-related population, intervention, comparator, outcomes (PICO) questions:PICO 1: Should bone mineral-enhancing agents be used to prevent fall-related injuries in the elderly?PICO 2: Should hip protectors be used to prevent fall-related injuries in the elderly?PICO 3: Should exercise programs be used to prevent fall-related injuries in the elderly?PICO 4: Should physical environment modifications be used to prevent fall-related injuries in the elderly?PICO 5: Should risk factor screening be used to prevent fall-related injuries in the elderly?PICO 6: Should multiple interventions tailored to the population or individual be used to prevent fall-related injuries in the elderly? METHODS: A comprehensive search and review of all the available literature was performed. We used the GRADE methodology to assess the breadth and quality of the data specific to our PICO questions. RESULTS: We reviewed 50 articles that met our inclusion and exclusion criteria as they applied to our PICO questions. CONCLUSION: Given the data constraints, we offer the following suggestions and recommendations:PICO 1: We conditionally recommend vitamin D and calcium supplementation for frail elderly individuals.PICO 2: We conditionally recommend hip protectors for frail elderly individuals, in the appropriate environment.PICO 3: We conditionally recommend evidence-based exercise programs for frail elderly individuals.PICO 4: We conditionally recommend physical environment modification for frail elderly people.PICO 5: We conditionally recommend frailty screening for the elderly.PICO 6: We strongly recommend risk stratification with targeted comprehensive risk-reduction strategies tailored to particular high-risk groups. LEVEL OF EVIDENCE: Systematic review, level III"
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Accidentes por Caídas , Accidentes por Caídas/prevención & control , Accidentes Domésticos/prevención & control , Equipos de Seguridad , Accidentes Domésticos , Evaluación Geriátrica , Factores de Riesgo , Planificación Ambiental , Conservadores de la Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Terapia por EjercicioRESUMEN
Feature detection in biomedical signals is crucial for deepening our knowledge about the involved physiological processes. To achieve this aim, many analytic approaches can be applied but only few are able to deal with signals whose time dependent features provide useful clinical information. Among the biomedical signals, the electroretinogram (ERG), that records the retinal response to a light flash, can improve our comprehension of the complex photoreceptoral activities. The present study is focused on the analysis of the early response of the photoreceptoral human system, known as a-wave ERG-component. This wave reflects the functional integrity of the photoreceptors, rods and cones, whose activation dynamics are not yet completely understood. Moreover, since in incipient photoreceptoral pathologies eventual anomalies in a-wave are not always detectable with a "naked eye" analysis of the traces, the possibility to discriminate pathologic from healthy traces, by means of appropriate analytical techniques, could help in clinical diagnosis. In the present paper, we discuss and compare the efficiency of various techniques of signal processing, such as Fourier analysis (FA), Principal Component Analysis (PCA), Wavelet Analysis (WA) in recognising pathological traces from the healthy ones. The investigated retinal pathologies are Achromatopsia, a cone disease and Congenital Stationary Night Blindness, affecting the photoreceptoral signal transmission. Our findings prove that both PCA and FA of conventional ERGs, don't add clinical information useful for the diagnosis of ocular pathologies, whereas the use of a more sophisticated analysis, based on the wavelet transform, provides a powerful tool for routine clinical examinations of patients.
Asunto(s)
Electrorretinografía , Reconocimiento de Normas Patrones Automatizadas/métodos , Procesamiento de Señales Asistido por Computador , Defectos de la Visión Cromática/diagnóstico , Defectos de la Visión Cromática/genética , Análisis de Fourier , Humanos , Análisis de Componente Principal , Análisis de OndículasRESUMEN
Most biomedical signals are non-stationary. The knowledge of their frequency content and temporal distribution is then useful in a clinical context. The wavelet analysis is appropriate to achieve this task. The present paper uses this method to reveal hidden characteristics and anomalies of the human a-wave, an important component of the electroretinogram since it is a measure of the functional integrity of the photoreceptors. We here analyse the time-frequency features of the a-wave both in normal subjects and in patients affected by Achromatopsia, a pathology disturbing the functionality of the cones. The results indicate the presence of two or three stable frequencies that, in the pathological case, shift toward lower values and change their times of occurrence. The present findings are a first step toward a deeper understanding of the features of the a-wave and possible applications to diagnostic procedures in order to recognise incipient photoreceptoral pathologies.
Asunto(s)
Electrorretinografía/métodos , Estudios de Casos y Controles , Defectos de la Visión Cromática/fisiopatología , HumanosRESUMEN
The wavelet analysis is a powerful tool for analyzing and detecting features of signals characterized by time-dependent statistical properties, as biomedical signals. The identification and the analysis of the components of these signals in the time-frequency domain, give meaningful information about the physiological mechanisms that govern them. This article presents the results of the wavelet analysis applied to the a-wave component of the human electroretinogram. In order to deepen and improve our knowledge about the behavior of the early photoreceptoral response, including the possible activation of interactions and correlations among the photoreceptors, we have detected and identified the stable time-frequency components of the a-wave, using six representative values of luminance. The results indicate the occurrence of three frequencies lying in the range 20-200 Hz. The lowest one is attributed to the summed activities of the photoreceptors. The others are weaker and at low luminance one of them does not occur. We relate them to the response of the rods and the cones whose aggregate activities are non-linear and typically exhibit self-organization under selective stimuli. The identification of the stable frequency components and of their times of occurrence helps us to shine light about the complex mechanisms governing the a-wave. The present results are promising toward the assessment of more refined model concerning the photoreceptoral activities.
Asunto(s)
Electrorretinografía/métodos , Estimulación Luminosa , Células Fotorreceptoras/fisiología , Retina/fisiología , Humanos , Análisis de OndículasRESUMEN
The a-wave is one of the main issues of research in the field of ocular electrophysiology, since it is strictly connected with early photoreceptoral activities. The present study proposes mathematical methods that analyse this component in human subjects, and supports experimental evidence relating to possible correlations among the responses of photoreceptoral units under a light stimulus. The investigation is organized in two parts: the first part concerns the onset and the initial slope, up to the first minimum (about 10-15 ms), the second part deals with the main portion of the wave, up to about 30 ms. In both cases, the a-waves, recorded at various levels of luminance, have been fitted with a set of appropriate functions representing possible models of physiological behaviour which would take place in the early stages of phototransduction. The statistical nature of the underlying processes is also discussed. The results indicate that correlations occur in the early stages, whereas random processes are set up later.
Asunto(s)
Algoritmos , Diagnóstico por Computador/métodos , Electrorretinografía/métodos , Electrorretinografía/efectos de la radiación , Modelos Biológicos , Retina/fisiología , Retina/efectos de la radiación , Simulación por Computador , Relación Dosis-Respuesta a Droga , Humanos , Luz , Estimulación Luminosa/métodos , Células Fotorreceptoras/fisiología , Células Fotorreceptoras/efectos de la radiación , Dosis de RadiaciónAsunto(s)
Cateterismo Venoso Central/efectos adversos , Cateterismo de Swan-Ganz/efectos adversos , Traumatismo Múltiple/diagnóstico por imagen , Traumatismo Múltiple/terapia , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/terapia , Filtros de Vena Cava/efectos adversos , Accidentes de Tránsito , Anciano , Anciano de 80 o más Años , Cateterismo Venoso Central/instrumentación , Cateterismo Venoso Central/métodos , Cateterismo de Swan-Ganz/instrumentación , Cateterismo de Swan-Ganz/métodos , Diseño de Equipo , Falla de Equipo , Femenino , Humanos , Traumatismo Múltiple/complicaciones , Radiografía , Factores de Riesgo , Traumatismos Torácicos/complicaciones , Factores de Tiempo , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & controlRESUMEN
Activation of P2x-purinoceptors in the nucleus tractus solitarius (NTS) via microinjection of alpha,beta-methylene ATP (alpha,beta-MeATP) elicits large dose-dependent decreases in mean arterial pressure (MAP) and heart rate (HR) and preferential dilation of the iliac vascular bed in comparison to renal and mesenteric vascular beds. We investigated whether sympathoinhibition contributes to the depressor responses and whether differential changes in regional sympathetic output occur. In 43 chloralose/urethane anesthetized male Sprague-Dawley rats, MAP, HR, renal (RSNA) and lumbar sympathetic nerve activity (LSNA) were recorded. Data were analyzed as both the maximum decrease and the integral of the decrease over the duration of the depressor response. Microinjection of alpha,beta-MeATP (25 and 100 pmol in 50 nl volume) into the subpostremal NTS caused significant and dose-dependent decreases in MAP, HR, RSNA and LSNA. However, the changes in RSNA were significantly greater than those observed in LSNA for both doses and both methods of analysis of data (maximum responses in delta %: 84 +/- 3 vs 62 +/- 4, and 93 +/- 3 vs 74 +/- 4 for low and high dose of alpha,beta-MeATP, respectively; integral responses in delta % x min: 32 +/- 4 vs 18 +/- 3 and 179 +/- 7 vs 134 +/- 14 for low and high dose of alpha,beta-MeATP, respectively). Blockade of P2-purinoceptors in the NTS by the specific P2-receptor antagonist suramin abolished responses to 100 pmol alpha,beta-MeATP and microinjections of vehicle did not alter neural nor hemodynamic parameters. We conclude that activation of P2x-purinoceptors in the NTS inhibits sympathetic nerve activity and evokes differential regional sympathetic responses. However, differential sympathoinhibition does not explain differential vascular responses to the activation of P2x-purinoceptors in the NTS.
Asunto(s)
Adenosina Trifosfato/análogos & derivados , Riñón/efectos de los fármacos , Receptores Purinérgicos/efectos de los fármacos , Núcleo Solitario/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Adenosina Trifosfato/farmacología , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Rat dorsomedial medullary brain segments containing primarily nucleus tractus solitarius (NTS) were employed for slice superfusion studies of electrically evoked [3H]serotonin ([3H]5-HT) release. Individual slices loaded with [3H]5-HT were stimulated two times, S1 and S2, at 3 Hz, 25 mA, 2 ms pulses for 1 min. Control NTS slices had a S2/S1 ratio of 0.94 (+/- 0.02). Superfusion of tissue slices with 0.1 nM to 100 nM 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), a selective adenosine A2a receptor agonist, for 5 min prior to the S2 stimulus produced a significant concentration-dependent increase in the S2/S1 fractional release ratio which was maximal (37.2% increase, P < 0.01) at 1.0 nM. However, superfusion of tissue slices with CGS 21680 over the same concentration range for 20 min prior to the S2 stimulus did not significantly alter the S2/S1 ratio from control release ratios. The augmented release of [3H]5-HT mediated by 1.0 nM CGS 21680 with 5 min tissue exposure was abolished by 1.0 nM 9-chloro-2-(2-furanyl)-5, 6-dihydro-[1,2,4]-triazolo[1,5-c]quinazolin-5-imine (CGS 15943) as well as by 100 nM 8-(3-chlorostyryl)caffeine (CSC), both A2a receptor antagonists, but not by 1.0 nM 8-cyclopentyl-1,3,-dipropylxanthine (DPCPX), the A1 receptor antagonist. These results indicate that CGS 21680 augmented the evoked release of [3H]5-HT in the NTS by way of activation of presynaptic adenosine A2a receptors. It was also apparent that this population of adenosine A2a receptors in the NTS desensitized within 20 min since the augmenting action of CGS 21680 on evoked transmitter release was not evident at the longer time interval.
Asunto(s)
Adenosina/análogos & derivados , Fenetilaminas/farmacología , Receptores Purinérgicos P1/fisiología , Serotonina/metabolismo , Núcleo Solitario/fisiología , Adenosina/farmacología , Animales , Técnicas In Vitro , Cinética , Masculino , Agonistas del Receptor Purinérgico P1 , Quinazolinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P1/efectos de los fármacos , Núcleo Solitario/efectos de los fármacos , Triazoles/farmacología , Xantinas/farmacologíaRESUMEN
The nucleus tractus solitarius (NTS) is a major integrative site in the brain stem involved in central autonomic control. Several lines of evidence indicate that ATP, acting at P2x purinoceptors, and adenosine, acting at A2a adenosine (P1) purinoceptors, play synchronous roles as transmitter substances in NTS-mediated mechanisms of cardiovascular control. The purpose of this study was to examine regional vascular response patterns elicited by selective activation of purinergic receptor subtypes in the NTS. Adult male rats were anesthetized with a mixture of alpha-chloralose and urethane. Pulsed-Doppler flow probes were placed on the iliac, renal and superior mesenteric arteries via a midline laparotomy for measurement of regional blood flow velocities. The animal was then mounted prone in a stereotaxic unit and the dorsal surface of the medulla was surgically exposed in the region of the obex. Microinjections of alpha, beta-methylene ATP (alpha,beta-MeATP), a selective P2x purinergic receptor agonist, or 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), a selective A2a adenosine (P1) receptor agonist, were made into the subpostremal region of the NTS via multibarrel glass micropipettes. Both alpha,beta-MeATP (25 and 100 pmoles/rat) and CGS 21680 (2 and 20 pmoles/rat) produced significant dose-related reductions in blood pressure and heart rate. These agonist-elicited depressor response patterns were associated with a pronounced and preferential dilation of the iliac vascular bed. However, alpha, beta-MeATP, but not CGS 21680, also caused significant dilation of the renal and superior mesenteric vascular beds, although lesser in magnitude compared to the iliac bed, whereas the hypotensive actions of CGS 21680 were considerably more prolonged compared to the very rapid and transient effects of alpha,beta-MeATP. These results support the view that extracellular ATP and adenosine via synchronous actions at specific purinergic receptor subtypes in the NTS may be functionally linked as neural signalling substances to selectively coordinate the regulation of regional vasomotor tone.
Asunto(s)
Sistema Cardiovascular/inervación , Receptores Purinérgicos/fisiología , Núcleo Solitario/química , Núcleo Solitario/fisiología , Adenosina/análogos & derivados , Adenosina/farmacología , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Anestesia , Animales , Antihipertensivos/farmacología , Barorreflejo/fisiología , Química Encefálica/fisiología , Fenómenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/efectos de los fármacos , Masculino , Microinyecciones , Fenetilaminas/farmacología , Agonistas Purinérgicos , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
5'-N-Ethylcarboxamidoadenosine (NECA) a non-selective adenosine A1 and A2a receptor agonist was employed in stimulated (3 Hz, 25 mA, 1 min) superfused nucleus tractus solitarius (NTS) brain slices loaded with [3H]5-hydroxytryptamine ([3H]5-HT), and ligand binding with [3H]NECA on NTS membranes. Superfusion of NTS slices with 1.0 and 3.0 nM NECA for 5 min prior to S2 stimulation produced an augmented release of [3H]5-HT (35.7%) above the control S2/S1 ratio. When the duration of NECA perfusion was increased to 20 min prior to S2, the S2/S1 ratio was depressed 21% at 1.0 nM for [3H]5-HT release. The augmented release of [3H]5-HT by NECA at 5 min was blocked by the adenosine A2a antagonist 8-(3-chlorostyryl)caffeine (CSC; 100 nM), and was reduced but not blocked by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 nM). Saturation binding assays with [3H]NECA on NTS membranes showed two binding sites, a high affinity site with a KD 2.18 nM and low affinity site with a KD of 44.9 nM. With the selective adenosine A2a antagonist CSC the high affinity site was blocked while 10 nM DPCPX, the A1 antagonist, reduced binding of the low affinity site, but did not abolish it. NECA binds to two different adenosine receptor sites in NTS membranes with the A2a receptor being the high affinity site. The same A2a site is associated with the augmented neurotransmitter release of [3H]5-HT with 5 min tissue exposure since it is blocked by CSC. Longer tissue exposure to NECA resulted in desensitization and finally inhibition of release possibly associated with adenosine A1 receptors.
Asunto(s)
Adenosina/análogos & derivados , Serotonina/metabolismo , Núcleo Solitario/química , Vasodilatadores/farmacología , 2-Cloroadenosina/farmacología , Acetilcolina/metabolismo , Adenosina/farmacología , Adenosina-5'-(N-etilcarboxamida) , Análisis de Varianza , Animales , Antihipertensivos/farmacología , Unión Competitiva/fisiología , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Masculino , Neurotransmisores/metabolismo , Técnicas de Cultivo de Órganos , Fenetilaminas/farmacología , Agonistas del Receptor Purinérgico P1 , Ratas , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT2A , Receptores de Serotonina/metabolismo , Sensibilidad y Especificidad , Serotonina/farmacología , Núcleo Solitario/metabolismo , Tritio , Xantinas/farmacología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Dorsal medullary brain slices containing primarily the nucleus tractus solitarius (NTS) were obtained from normal or 40- to 50-day streptozotocin-diabetic rats and employed for superfusion studies of evoked transmitter release. Electrically stimulated (25 mA, 2-ms pulses, 3 Hz, 1 min) release of [3H]norepinephrine ([3H]NE) or [3H]5-hydroxytryptamine ([3H]5-HT) from 400-microns NTS slices stimulated at 75 min (S1) and 130 min (S2) resulted in S2/S1 release ratios that were not different between normal controls or diabetic control groups. Perfusion of normal [3H]NE-loaded slices with 0.1 mumol/l clonidine reduced the S2/S1 ratio by 23% (p < 0.05) which was uniform in the caudal, subpostremal, and intermediate segment levels of the NTS. In diabetic NTS slices, the S2/S1 ratio was significantly less reduced by clonidine in both the subpostremal (-3%) and intermediate (-11%) slice regions. Blockade of alpha 2-adrenoceptors with yohimbine (0.1 mumol/l) enhanced (p < 0.05) [3H]NE release (S2/S1 ratios) in slices from both normal and diabetic rats. Perfusion of [3H]NE-loaded slices with 5 mU/ml insulin did not affect S2 release. Evoked S2/S1 release ratios from NTS slices loaded with [3H]5-HT did not differ between normal control and diabetic control groups. Clonidine (0.1 mumol/l) reduced S2-evoked release in both normal (-30%) and diabetic (-44%) slices, but the groups were not different from each other. Superfusion with 5 mU/ml insulin did not alter S2/S1 ratios in normal [3H]5-HT loaded slices, but did increase the diabetic NTS slice S2/S1 ratio to 1.40 +/- 0.06 (p < 0.01). In summary, it appears that alpha 2-adrenoceptor-mediated inhibition of [3H]NE release in the NTS was selectively attenuated in a regionally specific manner in diabetic animals. Release inhibition may be associated with receptor downregulation in NTS regions associated with cardiovascular reflex transmission. Insulin superfusion augmented [3H]5-HT release in the diabetic NTS slices, possibly through increased transmitter synthesis or improved synaptic release.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Clonidina/farmacología , Diabetes Mellitus Experimental/metabolismo , Insulina/farmacología , Núcleo Solitario/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/fisiopatología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Estimulación Eléctrica , Masculino , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Serotonina/metabolismo , Núcleo Solitario/metabolismo , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
Rat medullary brain segments containing primarily nucleus tractus solitarius (NTS) were used for superfusion studies of evoked transmitter release and for isotherm receptor binding assays. Isotherm binding assays with [3H]CGS-21680 on membranes prepared from NTS tissue blocks indicated a single high-affinity binding site with a KD of 5.1 +/- 1.4 nM and a Bmax of 20.6 +/- 2.4 fmol/mg of protein. The binding density for [3H]CGS-21680 on NTS membranes was 23 times less than comparable binding on membranes from striatal tissue. Electrically stimulated (1 min at 25 mA, 2 ms, 3 Hz) release of [3H]norepinephrine ([3H]NE) from 400-microns-thick NTS tissue slices resulted in an S2/S1 ratio of 0.96 +/- 0.02. Superfusion of single tissue slices with 0.1-100 nM CGS-21680, a selective adenosine A2a receptor agonist, for 5 min before the S2 stimulus produced a significant concentration-dependent increase in the S2/S1 fractional release ratio that was maximal (31.3% increase) at 1.0 nM. However, superfusion of tissue slices with CGS-21680 over the same concentration range for 20 min before the S2 stimulus did not alter the S2/S1 ratio significantly from control release ratios. The augmented release of [3H]NE mediated by 1.0 nM CGS-21680 with a 5-min tissue exposure was abolished by 1.0 and 10 nM CGS-15943 as well as by 100 nM 8-(3-chlorostyryl)caffeine, both A2a receptor antagonists, but not by 1.0 nM 8-cyclopentyl-1,3-dipropylxanthine, the A1 receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Bulbo Raquídeo/metabolismo , Norepinefrina/metabolismo , Terminales Presinápticos/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacología , Animales , Técnicas In Vitro , Masculino , Fenetilaminas/farmacología , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Crude membrane preparations from the dorsomedial medulla and whole heart of adult rats were used to characterize muscarinic receptors (mChRs) in the nucleus tractus solitarius (NTS). Isotherm binding assays with [3H]quinuclidinyl benzilate ([3H]QNB) indicated a uniform population of muscarinic cholinergic receptors in both tissues with a Kd of 60.3 pM and a Bmax of 401 fmol/mg protein for NTS membranes while heart membranes had a Kd of 56.6 pM and a Bmax of 193 fmol/mg protein. Competitive binding assays with selective muscarinic antagonists on NTS membranes using 80 pM [3H]QNB showed the following relative Ki values consistent with M2 mChRs: atropine, 1.9 nM; methoctramine, 7.7 nM; 4-diphenylacetoxy-N-methylpiperidine methobromide, 9.4 nM; AF-DX 116, 87.6 nM; and pirenzepine, 657 nM. Similarly, two agonists, carbachol and oxotremorine, showed Ki values of 1.82 microM and 0.379 microM, respectively. All of the competitive binding assays exhibited Hill coefficients close to 1.0 and InPlot analysis showed a single binding site for each agonist and antagonist examined.
Asunto(s)
Receptores Muscarínicos/metabolismo , Núcleo Solitario/metabolismo , Animales , Unión Competitiva/efectos de los fármacos , Técnicas In Vitro , Masculino , Bulbo Raquídeo/metabolismo , Membranas/efectos de los fármacos , Membranas/metabolismo , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Miocardio/metabolismo , Quinuclidinil Bencilato/farmacocinética , Ratas , Ratas Sprague-Dawley , Receptores Muscarínicos/efectos de los fármacos , Núcleo Solitario/efectos de los fármacosRESUMEN
Rat brain slices containing the nucleus tractus solitarius loaded with [3H]5-hydroxytryptamine ([3H]5-HT) for superfusion were stimulated at (3 Hz, 25 mA, 1 min) resulting in fractional release ratios S2/S1 of 0.89 for [3H]5-HT in the presence of the serotonin uptake inhibitor 1.0 microM 6-nitroquipazine (6-NQ). alpha-Methylserotonin (alpha-Me-5-HT; 1.0 microM), a non-selective 5-HT1 and 5-HT2 receptor agonist, significantly reduced the S2/S1 ratio of [3H]5-HT without affecting the basal release ratios B2/B1 1.00 +/- 0.04. Without 6-NQ in the perfusion medium 1.0 microM alpha-Me-5-HT sharply increased the basal release B2/B1 to 2.21 (P < 0.01). In low Ca2+ medium the S2/S1 ratio was reduced to 0.06 and alpha-Me-5-HT promoted a B2/B1 release of 2.17 (P < 0.01). The 5-HT3 antagonist LY-278,584 did not block alpha-Me-5-HT induced basal release of [3H]5-HT. Both pindolol and LY-53,857 blocked the autoinhibitory effects of alpha-Me-5-HT, but only LY-53,857 and 6-NQ blocked the basal release induced by alpha-Me-5-HT. These results suggest that alpha-Me-5-HT reduces neurotransmitter release through the serotonin autoreceptor and displaces serotonin through a non-exocytotic release mechanism.
Asunto(s)
Receptores Presinapticos/metabolismo , Agonistas de Receptores de Serotonina/farmacología , Serotonina/análogos & derivados , Serotonina/metabolismo , Núcleo Solitario/metabolismo , Animales , Unión Competitiva/efectos de los fármacos , Cloruros/metabolismo , Técnicas In Vitro , Masculino , Potasio/metabolismo , Ratas , Ratas Wistar , Receptores Presinapticos/efectos de los fármacos , Serotonina/farmacología , Agonistas de Receptores de Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Sodio/metabolismo , Núcleo Solitario/efectos de los fármacosRESUMEN
Rat brain slices from the dorsomedial medulla containing the nucleus tractus solitarius were loaded with [3H]norepinephrine ([3H]NE) for superfusion. Electrical stimulation (3 Hz, 25 mA, 1 min) resulted in fractional release ratios S2/S1 of 0.97 +/- 0.02 in normal Krebs-Henseleit (KH) and 0.93 +/- 0.06 in the presence of 30 microM cocaine. With cocaine in the KH medium, L-alpha-methylnorepinephrine (alpha-MeNE) significantly reduced the [3H]NE release S2/S1 without affecting the basal release ratios. Without cocaine in the KH medium both 0.1 and 1.0 microM alpha-MeNE increased the basal release B2/B1 that was not affected by yohimbine. Prazosin had no effect on the S2/S1 ratio but did attenuate the basal release effects of alpha-MeNE. In low Ca2+ studies where the S2 stimulus was abolished, 1.0 microM alpha-MeNE induced a sharply elevated increase in the B2/B1 ratio. It appears that alpha-MeNE in the presence of the uptake inhibitors reduces presynaptic neurotransmitter release through alpha 2-adrenoceptors, whereas when uptake of the monoamines was not blocked alpha-MeNE was considerably more efficacious as a displacing agent of neurotransmitter.
Asunto(s)
Nordefrin/metabolismo , Norepinefrina/metabolismo , Núcleo Solitario/metabolismo , Animales , Calcio/metabolismo , Cocaína/farmacología , Masculino , Ratas , Núcleo Solitario/efectos de los fármacos , Tiramina/farmacología , Yohimbina/farmacologíaRESUMEN
Potent and highly selective adenosine A1 and A2 receptor agonists were bilaterally injected into the nucleus accumbens of mice 10 min prior to inhibitory avoidance training. Retention of the inhibitory avoidance response was assessed 24 h after training. Intra-ACB activation of A1 receptors, but not A2a receptor activation, significantly impaired the performance of mice during the subsequent retention test. Furthermore, the retention deficit produced by activation of A1 receptors was significantly attenuated by pretreating mice with a highly selective A1 receptor antagonist. These findings suggest that endogenous adenosine may modulate information processing in the ventral striatum via adenosine A1 receptors.
Asunto(s)
Reacción de Prevención/fisiología , Inhibición Neural/fisiología , Núcleo Accumbens/fisiología , Receptores Purinérgicos P1/fisiología , Adenosina/análogos & derivados , Adenosina/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Mapeo Encefálico , Electrochoque , Miedo/efectos de los fármacos , Miedo/fisiología , Masculino , Recuerdo Mental/efectos de los fármacos , Recuerdo Mental/fisiología , Ratones , Ratones Endogámicos ICR , Inhibición Neural/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Fenetilaminas/farmacología , Receptores Purinérgicos P1/clasificación , Receptores Purinérgicos P1/efectos de los fármacosRESUMEN
The purpose of the study was to examine the role of P2 purinergic receptors in mechanisms of cardiovascular control mediated by the nucleus tractus solitarius (NTS), a major integrative site in the brainstem involved in the reflex coordination of cardiorespiratory and visceral response patterns. Microinjections of ATP and its analogues were made into the subpostremal NTS of anesthetized, spontaneously breathing rats. ATP, alpha,beta-methylene ATP (alpha beta-meATP) and 2-methylthio-ATP (2-meSATP) produced significant dose-related reductions in arterial blood pressure. alpha beta-meATP was slightly more potent than ATP and 2-meSATP. Pretreatment with the P2 receptor antagonist, suramin (0.5 nmol/rat), into the same NTS site 10 min prior to agonist administration completely blocked pronounced depressor response pattern elicited by the highest dose of alpha beta-meATP (0.1 nmol/rat). The present findings suggest that endogenous ATP may serve as a fast transmitter substance in NTS-mediated mechanisms of cardiovascular control.
Asunto(s)
Receptores Purinérgicos P2/efectos de los fármacos , Núcleo Solitario/fisiología , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Animales , Depresión Química , Hemodinámica/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Microinyecciones , Antagonistas del Receptor Purinérgico P2 , Ratas , Ratas Sprague-Dawley , Núcleo Solitario/efectos de los fármacos , Suramina/farmacología , Tionucleótidos/farmacologíaRESUMEN
Adult male mice were stereotaxically implanted with permanent indwelling guide cannulae for bilateral injections into the nucleus accumbens (ACB). The effects on spontaneous locomotor activity of selective agonists for adenosine receptor subtypes were examined following bilateral injections into the ACB. Intra-ACB injections of CGS 21680, a potent and selective agonist at striatal adenosine A2a receptors, elicited pronounced, dose-related reductions in locomotor activity whereas similar bilateral dosages of CPA, a selective agonist at adenosine A1 receptors, did not significantly affect locomotor activity. The pronounced locomotor depression elicited by intra-ACB injections of CGS 21680 were completely blocked by I.P. pretreatment with DMPX, an adenosine receptor antagonist exhibiting selectivity for striatal A2 receptors, at a dosage which alone had no significant effect on locomotor activity. Adenosine A2a receptors in the nucleus accumbens may selectively modulate dopamine-mediated mesolimbic behavioral circuits involved in spontaneous locomotion.
Asunto(s)
Núcleo Accumbens/fisiología , Receptores Purinérgicos P1/fisiología , Adenosina/administración & dosificación , Adenosina/análogos & derivados , Adenosina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Inyecciones , Masculino , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Fenetilaminas/administración & dosificación , Fenetilaminas/farmacología , Antagonistas de Receptores Purinérgicos P1 , Teobromina/análogos & derivados , Teobromina/farmacologíaRESUMEN
Neuropeptide Y (NPY) has been shown to be localized in a number of CNS regions, including the nucleus tractus solitarius (NTS). In this meeting report, a brief overview is presented of recent studies from our laboratory examining the role of NPY in NTS-mediated mechanisms of cardiorespiratory and visceroendocrine regulation. Microinjections of NPY, NPY analogs, or C-terminal NPY fragments were made into the subpostremal NTS of anesthetized spontaneously breathing rats. NPY elicited pronounced dose-related depressor responses, bradycardia, and reductions in respiratory minute volume. The overall cardiorespiratory response pattern elicited by NPY was mimicked by NPY, a fragment of NPY exhibiting selective agonist properties at presynaptic Y2 receptors, whereas the Y1 receptor-selective analog, [Leu31,Pro34]NPY, and the C-terminal inactive fragment, NPY, were found to be ineffective. In an effort to further characterize intrinsic NTS mechanisms mediating the NPY-evoked response pattern, NPY microinjections were similarly made in a group of rats with bilateral glossopharyngeovagotomy (G-vagotomy) and in a group of rats decerebrated at the supracollicular level. The results showed that whereas decerebration did not appreciably affect the NTS-mediated cardiorespiratory responses elicited by NPY, G-vagotomy enhanced the NPY-evoked hypotension while at the same time abolishing the NPY-evoked bradycardia and reductions in tidal volume. Taken together, these observations with G-vagotomized animals, along with the results from microinjection studies using selective ligands for NPY receptors, suggest that NPY may modulate primary visceral afferent information via activation of Y2 receptors distributed at presynaptic sites in the subpostremal NTS.(ABSTRACT TRUNCATED AT 250 WORDS)