RESUMEN
Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSanté, Haiti's national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSanté EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings.
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Registros Electrónicos de Salud/organización & administración , Sistemas de Información en Salud/organización & administración , Implementación de Plan de Salud , Recursos en Salud , Exactitud de los Datos , Haití , Humanos , Áreas de PobrezaRESUMEN
OBJECTIVES: Strong data quality (DQ) is a precursor to strong data use. In resource limited settings, routine DQ assessment (DQA) within electronic medical record (EMR) systems can be resource-intensive using manual methods such as audit and chart review; automated queries offer an efficient alternative. This DQA focused on Haiti's national EMR - iSanté - and included longitudinal data for over 100,000 persons living with HIV (PLHIV) enrolled in HIV care and treatment services at 95 health care facilities (HCF). METHODS: This mixed-methods evaluation used a qualitative Delphi process to identify DQ priorities among local stakeholders, followed by a quantitative DQA on these priority areas. The quantitative DQA examined 13 indicators of completeness, accuracy, and timeliness of retrospective data collected from 2005 to 2013. We described levels of DQ for each indicator over time, and examined the consistency of within-HCF performance and associations between DQ and HCF and EMR system characteristics. RESULTS: Over all iSanté data, age was incomplete in <1% of cases, while height, pregnancy status, TB status, and ART eligibility were more incomplete (approximately 20-40%). Suspicious data flags were present for <3% of cases of male sex, ART dispenses, CD4 values, and visit dates, but for 26% of cases of age. Discontinuation forms were available for about half of all patients without visits for 180 or more days, and >60% of encounter forms were entered late. For most indicators, DQ tended to improve over time. DQ was highly variable across HCF, and within HCFs DQ was variable across indicators. In adjusted analyses, HCF and system factors with generally favorable and statistically significant associations with DQ were University hospital category, private sector governance, presence of local iSante server, greater HCF experience with the EMR, greater maturity of the EMR itself, and having more system users but fewer new users. In qualitative feedback, local stakeholders emphasized lack of stable power supply as a key challenge to data quality and use of the iSanté EMR. CONCLUSIONS: Variable performance on key DQ indicators across HCF suggests that excellent DQ is achievable in Haiti, but further effort is needed to systematize and routinize DQ approaches within HCFs. A dynamic, interactive "DQ dashboard" within iSanté could bring transparency and motivate improvement. While the results of the study are specific to Haiti's iSanté data system, the study's methods and thematic lessons learned holdgeneralized relevance for other large-scale EMR systems in resource-limited countries.
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Exactitud de los Datos , Registros Electrónicos de Salud/organización & administración , Registros Electrónicos de Salud/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Estudios de Evaluación como Asunto , Femenino , VIH/patogenicidad , Infecciones por VIH/diagnóstico , Haití , Servicios de Salud , Humanos , Masculino , Embarazo , Estudios RetrospectivosRESUMEN
INTRODUCTION: The functional neuroanatomy of the egocentric and allocentric representations of space remains poorly studied with neuroimaging. Here we aim to determine brain structures subserving two different kinds of spatial representations centred on the main axis of either the body or the external scene. METHOD: Sixteen healthy participants evaluated the alignment of a bar relative to the middle of their body (Ego) or relative to another stimulus (Allo) during functional MRI. In a control task (Ctrl), they had to judge the colour of the bar. RESULTS: Correct response rates and response times were similar in the three tasks. fMRI data revealed a predominant role of the right hemisphere in the egocentric task (Ego vs. Allo): selective activity was found in the occipital, superior parietal, and inferior frontal cortices, as well as in the precuneus and supplementary motor area. On the left side, the insula, thalamus, and cerebellum were also activated. Conversely, the allocentric task (Allo vs. Ctrl) showed selective activity centred on the left temporal gyrus. DISCUSSION: This study demonstrates a right hemisphere dominance for representations centred on the longitudinal body axis, but more left-sided activity for scene/object-centred representations of space. These new data shed light on the unique role of several regions involved in spatial perception and help better understand spatial deficits in patients with right hemispheric lesions.
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Imagen Corporal , Encéfalo/fisiología , Percepción Espacial/fisiología , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
OBJECTIVE: Multimodal perception raises the issue of sensory integration. The aim of this study is to assess whether the visuo-haptic subjective vertical could be predicted from the visual and haptic unimodal performances, according to a Bayesian model, which optimizes the reliability of the multimodal estimate. The limits of the model were assessed by evaluating the impact of aging, cerebral damage and spatial deficits. METHOD: Young and older healthy participants, as well as patients with a right hemisphere lesion, suffering from spatial neglect or not, had to align a rod with the gravitational vertical in the visual, haptic and visuo-haptic modalities. RESULTS: Visuo-haptic subjective vertical was correctly predicted by the model in healthy participants, as well as in patients in spite of different performances. An anticlockwise deviation of the subjective vertical was observed in the neglect group whatever the experimental conditions. By contrast, no deviation was observed in both non-neglect and healthy groups, for the visual and the visuo-haptic modalities. Nevertheless, the haptic subjective vertical was deviated, anticlockwise in the non-neglect patients and older healthy adults, and clockwise in the young healthy adults. Moreover, the variance was the smallest in the bimodal condition. CONCLUSION: The integration of visual and haptic signals appeared to obey a Bayesian model optimizing the reliability of the multimodal estimate. This holds true despite of aging, brain damage or visuospatial disorders. Regarding the perception of the vertical, multisensory integration does not seem thus to depend only on right posterior cortical areas.
Asunto(s)
Lesiones Encefálicas/psicología , Trastornos de la Percepción/psicología , Percepción Espacial , Percepción del Tacto , Percepción Visual , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We review changes in body representation in patients with brain hemisphere damage and discuss their relationship with impaired limb movements in peripersonal space, navigation between objects/obstacles and control of the body's general posture and balance. The egocentric representation of the body's median sagittal axis (considered as the main zone around which movements are anchored) has been studied in most detail. This reference is distorted in patients with spatial neglect and involves a combination of ipsilesional translation and contralesional tilt. There are clear links with the patients' difficulties in egocentric tasks, activities of daily living and postural control. In both healthy subjects and patients, this reference axis can be modulated by somaesthetic, vestibular and visual stimulations; these phenomena have been used in rehabilitation programmes to reduce disease-induced deviations. A few studies have analyzed other lateral body reference (at the shoulders, in particular). These references were found to be more severely affected than the body midline (notably on the contralesional side). The severity of the distortion was related to the presence of lesions that mainly affected the parietal, somatosensory and multimodal association cortex (notably around the intraparietal sulcus) and, to a lesser extent, the middle temporal and frontal dorsolateral premotor cortex. These convergent results suggested that patients (notably those with neglect) have a complex distortion of the body schema and the perceptive representations of the body, that does not simply correspond to poor awareness of the contralateral hemicorpus.
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Imagen Corporal , Lesiones Encefálicas/psicología , Trastornos Psicomotores/psicología , HumanosRESUMEN
It is shown that the conductance relaxations observed in electrical field effect measurements on granular Al films are the sum of two contributions. One is sensitive to gate voltage changes and gives the already reported anomalous electrical field effect. The other one is independent of the gate voltage history and starts when the films are cooled down to low temperature. Their relative amplitude is strongly thickness-dependent which demonstrates the existence of a finite screening length in our insulating films and allows its quantitative estimate (about 10 nm at 4 K). This metalliclike screening should be taken into account in the electron glass models of disordered insulators.
RESUMEN
In spatial neglect, the pathological ipsilesional deviation of the subjective straight ahead (SSA) received both 'translational' and 'rotational' interpretations. Furthermore, hemianopia per se could also influence straight-ahead (SA) perception. Here, we aimed at disentangling the relative effects of neglect and hemianopia on the SSA by using a method analyzing translation and rotation in parallel. We included patients with a right hemisphere stroke. Ten had neglect and hemianopia, 6 neglect only, 3 hemianopia only, and 12 neither one nor the other. 15 were controls. Participants had to adjust a bar, movable in translation and rotation, SA of the navel, in darkness. Patients with spatial neglect showed systematic rightward translation, greater when hemianoptic. The rotation component appeared more variable and was influenced by the presence of a visual field defect, as most of the patients with hemianopia showed an anticlockwise rotation and most of the patients without hemianopia a clockwise rotation. Non-neglect patients and control subjects demonstrated a fair performance level. In conclusion, both neglect and hemianopia resulted in a translation error of the SSA to the ipsilesional side. In neglect patients, additional hemianopia resulted in a counterclockwise rotation. Furthermore, rotation and translation errors appeared dissociated, suggesting a different coding of these dimensions by the right posterior hemisphere.
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Lateralidad Funcional/fisiología , Cabeza/inervación , Hemianopsia/fisiopatología , Trastornos de la Percepción/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Mapeo Encefálico , Femenino , Cabeza/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: The contribution of endothelin-1 (ET-1) to vascular hyper-reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated. EXPERIMENTAL APPROACH: The biphasic haemodynamic responses to ET-1 (0.01-0.1 nmol kg(-1), i.v.) or to the selective ETB agonist, IRL1620 (0.001-1.0 nmol kg(-1), i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp-Dasp-Pro-Dval-Leu)) at 1 and 2.5 mg kg(-1) and BQ788 (N-cis-2,6-dimethyl-piperidinocarbonyl-L-gamma-methylleucyl1-D-1methoxycarbonyltryptophanyl-D-norleucine) at 0.25 mg kg(-1), respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined. KEY RESULTS: The initial hypotensive responses to ET-1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET-1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg(-1) reduced the pressor responses to ET-1 in ethanol-treated rats. Conversely, BQ788 (0.25 mg kg(-1)) potentiated ET-1-induced increases in mean arterial blood pressure in control as well as in ethanol-treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET-1 at a dose of 0.025 mg kg(-1) were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol. CONCLUSIONS AND IMPLICATIONS: Increased vascular reactivity to ET-1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.
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Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedades Cardiovasculares/etiología , Endotelina-1/metabolismo , Etanol/toxicidad , Receptor de Endotelina A/efectos de los fármacos , Receptor de Endotelina B/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Acetilcolina/farmacología , Consumo de Bebidas Alcohólicas/metabolismo , Consumo de Bebidas Alcohólicas/fisiopatología , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Endotelinas/farmacología , Etanol/administración & dosificación , Etanol/sangre , Frecuencia Cardíaca/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/metabolismo , Miocardio/metabolismo , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Péptidos Cíclicos/farmacología , Fenilefrina/farmacología , Piperidinas/farmacología , Ratas , Ratas Wistar , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Autoadministración , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: The subjective straight ahead (SSA), a measure of the representation of body orientation, has been shown to be shifted to the lesion side in neglect patients, and to be influenced by stimulation of sensory systems involved in postural control. METHOD: This study investigates the influence of changing body orientation in the sagittal plane on the SSA in 21 patients with a right hemispheric lesion, of whom 12 had neglect, in comparison with six healthy control subjects. In order to quantify both horizontal components of SSA error (ie, yaw rotation and lateral shift), the study used a method requiring the alignment of a luminous rod with SSA. RESULTS: Neglect patients showed a significant rightward shift in the sitting position, which was greatly reduced in the supine position. No shift occurred in patients without neglect or in controls. Yaw rotation did not reach significance in any group. CONCLUSION: The data showed that the body centred frame of reference, mostly translated in neglect, is strongly improved in the supine position. Changing body orientation seems to be a convenient tool to correct the representation of body midline.
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Trastornos de la Percepción/fisiopatología , Trastornos de la Percepción/terapia , Postura , Percepción Espacial , Adulto , Anciano , Encéfalo/fisiopatología , Electrofisiología/instrumentación , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Percepción/etiología , Rotación , Accidente Cerebrovascular/complicaciones , Campos Visuales/fisiologíaRESUMEN
OBJECTIVE: To compare the angles of cyclotorsion measured by central campimetry and scanning laser ophthalmoscopy. METHODS: Both methods were applied to each eye of 44 healthy volunteers, aged between 22 and 55 years. The line passing through the fovea and the center of the papilla was drawn on images from the scanning laser ophthalmoscope (SLO); the line passing through the fixing point and the center of the blind spot was drawn on the charts of the central visual field (VF). Torsion was estimated by the angle between these lines and the horizontal. RESULTS: With the VF method, the excyclotorsion was 5.6+/-2.9 degrees on the right eye and 7.2+/-2.9 degrees on the left eye. With the SLO method, these values were 4.7+/-2.6 degrees and 6.8+/-2.5 degrees , respectively. The measures obtained with both methods correlated significantly, for the right eye and the left eye, as well as for the difference between them. CONCLUSION: Data were in good agreement with the literature. Though slightly greater, values obtained with the scanning laser ophthalmoscope were coherent with campimetric measures. The origin of the greater excyclotorsion of the left eye remains an open issue. This phenomenon must be kept in mind when looking for a pathological between-eye difference.
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Antropometría/métodos , Ojo/anatomía & histología , Oftalmoscopía , Campos Visuales , Adulto , Antropometría/instrumentación , Femenino , Humanos , Rayos Láser , Masculino , Persona de Mediana Edad , Oftalmoscopios , Oftalmoscopía/métodos , Valores de Referencia , Reproducibilidad de los Resultados , Anomalía TorsionalRESUMEN
We investigated the subjective straight-ahead (SSA) projection of body-midline parts (head and trunk) in patients with neglect and patients with nonneglect, using a method disentangling lateral shift and lateral tilt components of the bias. Patients with neglect showed a similar counterclockwise SSA tilt for each body part and an ipsilesional lateral shift, more severe for the trunk than for the head. Thus, neglect results in a tilt of the body midline representation.
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Atención , Imagen Corporal , Orientación , Trastornos de la Percepción/psicología , Percepción Espacial , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Patients with right-brain injury present, more frequently in the acute phase, with a deviation of the subjective vertical (SV) contralateral to the lesion. The aim of this study was to investigate the influence of galvanic vestibular stimulation (GVS) on this disorder. Twelve patients presenting with a right hemispheric lesion, seven with neglect (N+) and five without (N-) were compared to eight control subjects. They had to orient vertically a luminous rod in darkness, in three galvanic stimulation (1.5 mA) conditions: cathode left, cathode right and no stimulation (baseline). Without stimulation, the patients' SV, and especially that of N+, showed an anticlockwise deviation. In comparison with baseline values, GVS induced a deviation toward the side opposite to the cathode in the three groups. In the patients, the deviation was of larger amplitude and appeared greater for left than for right cathodic stimulation. In conclusion, we showed an influence of vestibular stimulation on the SV of right brain-injured patients, especially when spatial neglect was present. As left cathodic stimulation can reduce the SV deviation associated with spatial neglect, such a tool could be introduced in rehabilitation.
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Estimulación Eléctrica , Trastornos de la Percepción/fisiopatología , Trastornos de la Percepción/terapia , Percepción Espacial/fisiología , Vestíbulo del Laberinto/fisiopatología , Adulto , Anciano , Análisis de Varianza , Lesiones Encefálicas/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Percepción/etiologíaRESUMEN
The endothelin-converting enzyme (ECE) is the main enzyme responsible for the genesis of the potent pressor peptide endothelin-1 (ET-1). It is suggested that the ECE is pivotal in the genesis of ET-1, considering that the knockout of both genes generates the same lethal developments during the embryonic stage. Several isoforms of the ECE have been disclosed, namely ECE-1, ECE-2, and ECE-3. Within each of the first two groups, several sub-isoforms derived through splicing of single genes have also been identified. In this review, the characteristics of each sub-isoform for ECE-1 and 2 will be discussed. It is important to mention that the ECE is, however, not the sole enzyme involved in the genesis of endothelins. Indeed, other moieties, such as chymase and matrix metalloproteinase II, have been suggested to be involved in the production of ET intermediates, such as ET-1 (1-31) and ET-1 (1-32), respectively. Other enzymes, such as the neutral endopeptidase 24-11, is curiously not only involved in the degradation and inactivation of ET-1, but is also responsible for the final production of the peptide via the hydrolysis of ET-1 (1-31). In this review, we will attempt to summarize, through the above-mentioned characteristics, the current wisdom on the role of these different enzymes in the genesis and termination of effect of the most potent pressor peptide reported to date.
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Ácido Aspártico Endopeptidasas/metabolismo , Endotelina-1/biosíntesis , Secuencia de Aminoácidos/fisiología , Animales , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Endotelina-1/metabolismo , Enzimas Convertidoras de Endotelina , Inhibidores Enzimáticos/farmacología , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Metaloendopeptidasas , Datos de Secuencia MolecularRESUMEN
One of the two receptors by which the potent vasoactive effects of endothelin (ET)-1 are mediated is the ET(B) receptor (ET(BR)), which is found in several tissues, but, more importantly from a cardiovascular point of view, on the endothelial cell. The endothelial cell also has the unique capability of releasing ET-1, as well as other factors, such as the endothelial-derived relaxing factors and prostacyclin, which counteract the myotropic effects of the peptide. The secretory and contractile responses to ET-1 rely on G-protein-coupled ET(BR)s, as well as ET(A)-G-protein-coupled receptor-like proteins. The mitogenic properties of ET-1 via ET(A) receptors (ET(AR)s) coupled to mitogen-activated protein kinases and tyrosine kinases on the vascular smooth muscle may occur in conjunction with the anti-apoptotic characteristics of the endothelial ET(BR)s. Interestingly, most of the relevant antagonists and agonists for both ET(AR)s and ET(BR)s have been developed by the pharmaceutical industry. This highlights the therapeutical potential of compounds that act on ET receptors. In normal as well as in physiopathological conditions, the ET(BR) plays an important role in the control of vascular tone, and must be taken into account when using ET receptor antagonists for the treatment of cardiovascular diseases. For the management of congestive heart failure, renal failure and primary pulmonary hypertension, the most recent literature supports the use of selective ET(AR) antagonists rather than mixed antagonists of ET(AR)s and ET(BR)s. Nonetheless, validation of this view will have to await the first clinical trials comparing the actions of ET(A) to mixed ET(A)/ET(B) receptor antagonists.
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Enfermedades Cardiovasculares , Endotelina-1/fisiología , Receptores de Endotelina/fisiología , Animales , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Antagonistas de los Receptores de Endotelina , Humanos , Receptor de Endotelina B , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacosRESUMEN
The rightward orientation bias of neglect patients has been shown to be decreased by postural changes, suggesting that afferences coding the posture relative to gravity might influence the body-centred spatial reference frame. In order to test this hypothesis, we evaluated the effects of plantar stimulations on the subjective straight-ahead (SSA) of two neglect patients presenting with a strong rightward shift, as well as two non-neglect patients and three normal subjects. Vibratory or electrical stimulations were applied to the left or right plantar sole. Data showed that these manipulations influenced the SSA position in neglect patients only. The observed improvement could be explained by a direction-specific effect of vibration, in addition to a non-specific activation induced by both stimulations.
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Orientación/fisiología , Trastornos de la Percepción/fisiopatología , Estimulación Eléctrica Transcutánea del Nervio , Vibración , Adulto , Anciano , Análisis de Varianza , Femenino , Pie/fisiología , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Percepción/rehabilitación , Nervio Tibial/fisiologíaRESUMEN
1. We have developed a model to study the inhibitory properties of endogenous autacoids triggered by systemically-administered vasoactive peptides, on platelet aggregation ex vivo in the mouse. 2. Adenosine diphosphate (ADP) (0.5-10 microM) induces a concentration-dependent aggregation of platelet-rich plasma derived from C57BL/6 mice. Intravenously-administered endothelin-1 (0.01-1 nmolx kg(-1)), the selective ETB agonist, IRL-1620 (0.0 -1 nmol x kg(-1)) or bradykinin ( 1-100 nmol x kg(-1)) significantly reduced in a dose-dependent fashion the ADP-induced platelet aggregation. 3. The non-selective cyclo-oxygenase (COX) inhibitor, indomethacin, a selective COX-2 inhibitor NS-398 or the prostacyclin synthase inhibitor, tranylcypromine (10 mg x kg(-1)), markedly reduced the inhibitory properties of endothelin-1, whereas only a combination of both indomethacin, NS-398 or tranylcypromine and L-NAME (10 mg x kg(-1)) were required to abolish the response to bradykinin. 4. An ETB-selective antagonist (BQ-788) or knockout of the B2 receptor gene (in B2 knockout mice) abolishes the platelet inhibitory properties of endothelin-1 and bradykinin, respectively. 5. Our results suggest that intravenously-administered endothelin-1 and bradykinin, through ETB and B2 receptor activation, respectively, inhibit platelet aggregation ex vivo in the mouse. The inhibitory properties of endothelin-1 require the activation of COX-2 and the subsequent generation of prostacyclin. In addition to the two previously mentioned factors, nitric oxide is required for the anti-aggregatory effects of bradykinin.
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Endotelina-1/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Receptores de Bradiquinina/fisiología , Receptores de Endotelina/fisiología , Adenosina Difosfato/farmacología , Animales , Bradiquinina/farmacología , Ciclooxigenasa 2 , Relación Dosis-Respuesta a Droga , Indometacina/farmacología , Isoenzimas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico/fisiología , Agregación Plaquetaria/efectos de los fármacos , Prostaglandina-Endoperóxido Sintasas/fisiología , Receptor de Bradiquinina B2 , Receptor de Endotelina BRESUMEN
The distribution of mRNAs for endothelinA and B (ET(A) and ET(B)) receptors and their binding properties was studied in human nonpregnant and pregnant term myometrium and in uterine leiomyomas. ET(A)- and ET(B)-receptors functionally coupled to phospholipase C (PLC) coexisted in myometrial tissues, but only the functional ET(A)-receptor subtype was detected in leiomyomas. ET(A)-receptor mRNA and three other spliced variants were distributed in all tissue studied. We reported an increase in the proportion of ET(A)-receptors coupled to PLC in term pregnant myometrium when compared to nonpregnant tissue. These results suggest that upregulation of the myometrial ET(A)-receptors may account for or contribute to the control of normal development and growth of human myometrium during pregnancy. They also support a pathological role for the endothelin-1 (ET-1)/ET(A)-receptor system in leiomyoma development.
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Leiomioma/metabolismo , Miometrio/metabolismo , Embarazo/metabolismo , ARN Mensajero/análisis , Receptores de Endotelina/genética , Neoplasias Uterinas/metabolismo , Azepinas/farmacología , Endotelina-1/metabolismo , Femenino , Humanos , Indoles/farmacología , Oligopéptidos/farmacología , Piperidinas/farmacología , Receptor de Endotelina A , Receptor de Endotelina BRESUMEN
Neglect patients often present with a rightward shift of the direction straight-ahead of body midline. We investigated whether directions ahead of other body parts were similarly shifted or were differentially affected. Right brain-damaged patients, with and without neglect, and normal subjects had to indicate by manual pointings, the directions straight-ahead of the navel, the nose, the left and right shoulders. In neglect patients, constant errors varied across directions with a decrease in magnitude from left to right, suggesting a compression of body projection in extracorporeal space. Moreover, the projection of the left hemibody was smaller than the right in all subjects, with and without neglect. This unexpected finding is discussed with regard to other spatial asymmetries observed in normal subjects.