RESUMEN
OBJECTIVES: A persistent stapedial artery is a rare vascular malformation. This diagnosis is based on CT scan and intraoperative findings. MATERIAL AND METHODS: The case of a 19-year-old woman with a persistent stapedial artery found during stapes surgery is reported. This vascular malformation was explored with a CT scan showing the bilaterality of this anatomical variation and signs of associated otosclerosis. RESULTS: This malformation was successfully coagulated with laser allowing the stapedotomy to be completed. CONCLUSIONS: A persistent stapedial artery is not a contraindication to stapedotomy because it can be safely coagulated during the same procedure.
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Arterias/anomalías , Otosclerosis/diagnóstico por imagen , Otosclerosis/cirugía , Estapedio/irrigación sanguínea , Cirugía del Estribo , Tomografía Computarizada por Rayos X , Arterias/cirugía , Femenino , Perdida Auditiva Conductiva-Sensorineural Mixta/diagnóstico por imagen , Perdida Auditiva Conductiva-Sensorineural Mixta/cirugía , Pruebas Auditivas , Humanos , Coagulación con Láser , Otoscopía , Tendones/diagnóstico por imagen , Tendones/cirugía , Adulto JovenRESUMEN
BACKGROUND: Surveillance of surgical site infections (SSIs) is a core component of effective infection control practices, though its impact has not been quantified on a large scale. AIM: To determine the time-trend of SSI rates in surveillance networks. METHODS: SSI surveillance networks provided procedure-specific data on numbers of SSIs and operations, stratified by hospitals' year of participation in the surveillance, to capture length of participation as an exposure. Pooled and procedure-specific random-effects Poisson regression was performed to obtain yearly rate ratios (RRs) with 95% confidence intervals (CIs), and including surveillance network as random intercept. FINDINGS: Of 36 invited networks, 17 networks from 15 high-income countries across Asia, Australia and Europe participated in the study. Aggregated data on 17 surgical procedures (cardiovascular, digestive, gynaecological-obstetrical, neurosurgical, and orthopaedic) were collected, resulting in data concerning 5,831,737 operations and 113,166 SSIs. There was a significant decrease in overall SSI rates over surveillance time, resulting in a 35% reduction at the ninth (final) included year of surveillance (RR: 0.65; 95% CI: 0.63-0.67). There were large variations across procedure-specific trends, but strong consistent decreases were observed for colorectal surgery, herniorrhaphy, caesarean section, hip prosthesis, and knee prosthesis. CONCLUSION: In this large, international cohort study, pooled SSI rates were associated with a stable and sustainable decrease after joining an SSI surveillance network; a causal relationship is possible, although unproven. There was heterogeneity in procedure-specific trends. These findings support the pivotal role of surveillance in reducing infection rates and call for widespread implementation of hospital-based SSI surveillance in high-income countries.
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Monitoreo Epidemiológico , Control de Infecciones/métodos , Cooperación Internacional , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Asia/epidemiología , Australia/epidemiología , Europa (Continente)/epidemiología , Humanos , Incidencia , Estudios RetrospectivosRESUMEN
We report a case of a 9-month pregnant woman who presented acute psychiatric and neurological symptoms with extensive involvement of the white matter on MRI and no oligoclonal bands on CSF examination. Despite high doses of intravenous steroids, plasmapheresis and immunosuppressive drugs, a fatal outcome (coma) was noted 8 months later. Neuropathological examination confirmed the diagnosis of Marburg's type of multiple sclerosis showing sharp-edged lesions of demyelination, giant astrocytes, numerous macrophages and little perivascular inflammation. We discuss the definition and limits of the Marburg entity with reference to acute disseminated encephalomyelitis, impact of pregnancy, unusual MRI features, neuropathology and treatment.
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Encéfalo/patología , Encefalomielitis Aguda Diseminada/patología , Esclerosis Múltiple/patología , Complicaciones del Embarazo/patología , Enfermedad Aguda , Adulto , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Terapia de Inmunosupresión , Imagen por Resonancia Magnética , Esclerosis Múltiple/tratamiento farmacológico , Plasmaféresis , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Esteroides/uso terapéuticoRESUMEN
The state dependence of Na channel modification by batrachotoxin (BTX) was investigated in voltage-clamped and internally perfused squid giant axons before (control axons) and after the pharmacological removal of the fast inactivation by pronase, chloramine-T, or NBA (pretreated axons). In control axons, in the presence of 2-5 microM BTX, a repetitive depolarization to open the channels was required to achieve a complete BTX modification, characterized by the suppression of the fast inactivation and a simultaneous 50-mV shift of the activation voltage dependence in the hyperpolarizing direction, whereas a single long-lasting (10 min) depolarization to +50 mV could promote the modification of only a small fraction of the channels, the noninactivating ones. In pretreated axons, such a single sustained depolarization as well as the repetitive depolarization could induce a complete modification, as evidenced by a similar shift of the activation voltage dependence. Therefore, the fast inactivated channels were not modified by BTX. We compared the rate of BTX modification of the open and slow inactivated channels in control and pretreated axons using different protocols: (a) During a repetitive depolarization with either 4- or 100-ms conditioning pulses to +80 mV, all the channels were modified in the open state in control axons as well as in pretreated axons, with a similar time constant of approximately 1.2 s. (b) In pronase-treated axons, when all the channels were in the slow inactivated state before BTX application, BTX could modify all the channels, but at a very slow rate, with a time constant of approximately 9.5 min. We conclude that at the macroscopic level BTX modification can occur through two different pathways: (a) via the open state, and (b) via the slow inactivated state of the channels that lack the fast inactivation, spontaneously or pharmacologically, but at a rate approximately 500-fold slower than through the main open channel pathway.
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Axones/fisiología , Batracotoxinas/farmacología , Canales de Sodio/fisiología , Compuestos de Tosilo , Acetamidas/farmacología , Animales , Antiinfecciosos Locales/farmacología , Axones/efectos de los fármacos , Cloraminas/farmacología , Decapodiformes , Electrofisiología , Potenciales de la Membrana , Pronasa/farmacología , Canales de Sodio/efectos de los fármacosRESUMEN
We present four examples of attenuation of the transformed phenotype caused by the root-inducing, left-hand, transferred DNA from Agrobacterium rhizogenes in tobacco (Nicotiana tabacum). The first was associated with a genetic variable (homozygosity for the T-DNA), and the second was induced at the physiological level by putrescine and tyramine, suggesting that the transformed phenotype depends on defective polyamine metabolism. Physiological attenuation is further illustrated in the third example, in which the inhibition of flowering caused by P35S-rolA, a gene from the root-inducing, left-hand, transferred DNA driven by a strong viral promoter, was attenuated by grafting the transformed shoot onto non-transformed rootstock that had been induced to flower. Infertility in the resulting flowers was corrected by a mixture of putrescine and tyramine, indicating that P35S-rolA inhibited flowering through interference with polyamine conjugation and that tyramine was essential to fertility. A fourth example of attenuation of the transformed phenotype occurred in lateral branches of plants expressing rolA under the control of its native promoter. In these branches, reduction in the accumulation of rolA transcripts was correlated with the methylation of a site 3[prime] to the rolA coding sequence; thus, the transformed plant seems capable of recognizing and repressing a gene that interferes with flowering.
RESUMEN
Neuro-imaging is essential for the initial evaluation and subsequent control in the acute stage of severe head injury. In these indications tomodensitometry (TDM) has a pivotal role. Despite the well recognized contribution of magnetic resonance imaging (MRI) to the investigation of most of acute neurological pathologies, MRI is not still a routine procedure for the initial investigation of patients with acute head injury. The superiority of morphological and functional MRI on TDM in this indication is discussed.
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Lesiones Encefálicas/diagnóstico , Imagen por Resonancia Magnética/métodos , Enfermedad Aguda , Barrera Hematoencefálica , Edema Encefálico/diagnóstico , Edema Encefálico/etiología , Edema Encefálico/patología , Lesiones Encefálicas/clasificación , Lesiones Encefálicas/patología , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiología , Hemorragia Cerebral/patología , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/patología , Imagen de Difusión por Resonancia Magnética , Progresión de la Enfermedad , HumanosRESUMEN
Isthmic aortic rupture or disruption should be systematically sought when there is high kinetic energy trauma to the thorax. This condition is extremely serious and life threatening. It needs to be diagnosed rapidly but diagnostic pitfalls must be avoided. CT angiography is the standard examination. The main CT signs of rupture or disruption of the thoracic aorta are periaortic hematoma, intimal flap, pseudo-aneurysm and contrast agent extravasation. There are three types of lesion: intimal, subadventitial or pseudo-aneurysmal, and complete rupture with lesion of the three tunicae, and it is important to grade them for better therapeutic management. The main diagnostic pitfalls of the CT scan are the presence of a ductus diverticulum and post-isthmic fusiform dilatation. Associated lesions must not be overlooked. The most common are ruptures of the aortic root and the thoracic aorta in the diaphragmatic hiatus.
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Aorta Torácica/diagnóstico por imagen , Aorta Torácica/lesiones , Tomografía Computarizada por Rayos X , Lesiones del Sistema Vascular/diagnóstico por imagen , Angiografía/métodos , Aorta Torácica/cirugía , HumanosRESUMEN
Plant roots provide anchorage and absorb the water and minerals necessary for photosynthesis in the aerial parts of the plant. Since plants are sessile organisms, their root systems must forage for resources in heterogeneous soils through differential branching and elongation [(1988) Funct. Ecol. 2, 345-351; (1991) Plant Roots: The Hidden Half, pp. 3-25, Marcel Dekker, NY]. Adaptation to drought, for instance, can be facilitated by increased root growth and penetration. Root systems thus develop as a function of environmental variables and the needs of the plant [(1988) Funct. Ecol. 2, 345-351; (1986) Bot. Gaz. 147, 137-147; (1991) Plant Roots: The Hidden Half, pp. 309-330, Marcel Dekker, NY]. We show, in a model system consisting of excised tobacco roots, that both alpha-DL-difluoromethylornithine (an inhibitor of putrescine biosynthesis) and the rolA gene (from the root-inducing transferred DNA of Agrobacterium rhizogenes) stimulate overall root growth and cause a conversion in the pattern of root system formation, producing a dominant or 'tap' root. These morphological changes are correlated with a depression in the accumulation of polyamines and their conjugates.
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Ácidos Cumáricos/metabolismo , Nicotiana/crecimiento & desarrollo , Nicotiana/metabolismo , Plantas Tóxicas , Putrescina/análogos & derivados , Putrescina/metabolismo , Eflornitina/farmacología , Genes de Plantas , Modelos Biológicos , Plantas Modificadas Genéticamente , Rhizobium/genética , Nicotiana/genética , Transformación GenéticaRESUMEN
DFMO (alpha-DL-difluoromethylornithine), a specific irreversible inhibitor of ornithine decarboxylase (ODC), a polyamine biosynthetic pathway enzyme, strongly inhibits root growth and arbuscular mycorrhizal infection of Pisum sativum (P56 myc+, isogenic mutant of cv. Frisson). This inhibition is reversed when exogenous polyamine (putrescine) is included in the DFMO treatment, showing that the effect of DFMO on arbuscular mycorrhizal infection is indeed due to putrescine limitation and suggesting that ODC may have a role in root growth and mycorrhizal infection. However, treatment with gibberellic acid (GA3) which increased root titers of polyamines strongly inhibited arbuscular mycorrhizal development. The possible role of polyamines in the regulation of the development of arbuscular mycorrhizal infection is discussed.
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Hongos/fisiología , Giberelinas/farmacología , Pisum sativum/microbiología , Enfermedades de las Plantas , Poliaminas/metabolismo , Cadaverina/metabolismo , Eflornitina/farmacología , Inhibidores Enzimáticos/farmacología , Mutación , Inhibidores de la Ornitina Descarboxilasa , Pisum sativum/efectos de los fármacos , Pisum sativum/crecimiento & desarrollo , Pisum sativum/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Poliaminas/farmacología , Putrescina/metabolismo , Putrescina/farmacología , Espermidina/metabolismo , Espermina/metabolismoRESUMEN
Polyunsaturated fatty acids (PUFA) are important in pregnancy, fetal development and parturition. We measured free fatty acids (FFA), albumin and alpha-fetoprotein (AFP) in the maternal and fetal circulations of women undergoing elective Caesarean section at term. We also studied the impact of PUFAs on estrogen (ER) and progesterone receptors (PR) binding properties in vitro in the myometria of pregnant women and ex vivo in human myometrial cells in culture. FFA in intervillous blood (I) (feto-maternal interface) and maternal peripheral blood (M) were similar, while those in the umbilical vein (V) and arteries (A) were 2-4 fold lower (P<0.001). PUFA levels were low in M and 3 fold higher in I, A and V (P< 0.001); consequently C20:4 and C22:6 were most abundant in intervillous space. Albumin was uniformly distributed throughout the maternal-fetal unit, but there was a transplacental gradient in AFP. The AFP in the intervillous space had a special conformation (less immuno-reactive, more anionic), suggesting loading with PUFA. Physiological concentrations of C20:4 stimulated estradiol binding, but inhibited progestin binding. C20:4 inhibited progesterone binding by decreasing the number of binding sites, with no change in apparent affinity, in vitro in myometrial tissue and ex vivo in myometrial cells. Thus PUFA may modulate the steroid hormone message, so that the high C20:4 concentration at the maternal-fetal interface at term may help amplify the estrogen signal and inhibit the progesterone signal.
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Estrógenos/metabolismo , Ácidos Grasos Insaturados/sangre , Intercambio Materno-Fetal/fisiología , Proteínas de Neoplasias , Progesterona/metabolismo , Proteínas Supresoras de Tumor , alfa-Fetoproteínas/metabolismo , Proteínas Portadoras/sangre , Células Cultivadas , Estrógenos/fisiología , Proteína de Unión a los Ácidos Grasos 7 , Proteínas de Unión a Ácidos Grasos , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Proteína P2 de Mielina/sangre , Miometrio/metabolismo , Embarazo , Progesterona/fisiología , Unión Proteica , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Albúmina Sérica/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Three cases of extracranial vertebral artery dissections with upper limb peripheral motor deficit (C5-C6) are reported. Six similar cases were also found in the literature. Central neurological symptoms occurred in five of these nine cases, suggesting the diagnosis of dissection. The peripheral motor or sensorial deficit was strictly isolated in the four other cases, simulating radicular neuralgia due to discopathy or foraminal compression. In case of dissections, a precise analysis of pain is helpful to guide diagnosis; sharp, unbearable, continuous and extended neck pain without nocturnal paroxysms and posterior neck stiffness is typical. Analgesics or anti-inflammatory drugs are ineffective. Peripheral motor deficit is more common than sensory deficit. Recovery was complete in this series. In most cases, the radiculopathy appears to be due to cervical root compression in its extraforaminal course due to the dissection hematoma and rarely to radicular ischemia.
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Aneurisma Roto/complicaciones , Disección Aórtica/complicaciones , Síndromes de Compresión Nerviosa/etiología , Raíces Nerviosas Espinales , Arteria Vertebral , Adulto , Brazo/inervación , Ciclismo , Enfermedades de los Nervios Craneales/etiología , Diagnóstico Diferencial , Femenino , Hematoma/etiología , Humanos , Hipertensión/complicaciones , Hipoestesia/etiología , Masculino , Dolor de Cuello/etiología , Síndromes de Compresión Nerviosa/diagnóstico , Parálisis/etiología , Trastornos Puerperales/etiología , Radiculopatía/diagnóstico , Rotura Espontánea , Trastornos de la Visión/etiologíaRESUMEN
The persistent carotid-vertebrobasilar anastomoses (PCVBA) can be explained by an interruption of the vertebrobasilar system (VBS) embryogenesis. We present two very rare cases of persistent anastomoses: a hypoglossal artery and a type I proatlantal artery, insisting on the angiographic criteria allowing differentiation. After a brief review of the embryogenesis of the VBS, we describe the different types of persistent anastomoses (hypoglossal, type I and II proatlantal, trigeminal and otic arteries). We will insist on the potential risks, not well-known, but typical of each anastomosis. PCVBA usually are incidental findings but imaging follow-up may be required since aneurysms may develop.
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Aneurisma Roto/embriología , Arterias Carótidas/anomalías , Atlas Cervical/irrigación sanguínea , Nervio Hipogloso/irrigación sanguínea , Aneurisma Intracraneal/embriología , Malformaciones Arteriovenosas Intracraneales/embriología , Arteria Vertebral/anomalías , Aneurisma Roto/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/embriología , Cerebelo/irrigación sanguínea , Cerebelo/diagnóstico por imagen , Cerebelo/embriología , Diagnóstico Diferencial , Humanos , Nervio Hipogloso/diagnóstico por imagen , Nervio Hipogloso/embriología , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Radiografía , Nervio Trigémino/irrigación sanguínea , Nervio Trigémino/diagnóstico por imagen , Nervio Trigémino/embriología , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/embriologíaRESUMEN
BACKGROUND: Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. METHODS: We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. RESULTS: In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. CONCLUSIONS: A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis.
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Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Neoplasias Primarias Desconocidas/diagnóstico , Neuroimagen/métodos , Anciano , Biopsia con Aguja , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Isocitrato Deshidrogenasa/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/patología , Neoplasias Primarias Desconocidas/cirugía , Convulsiones/etiología , Resultado del TratamientoRESUMEN
Magnetic resonance imaging (MRI) is a method of choice for follow-up of irradiated brain metastasis. It is difficult to differentiate local tumour recurrences from radiation induced-changes in case of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and amino acid positron-emission tomography (PET) allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method. We report the case of a patient who underwent surgery for a single, left frontal brain metastasis of a breast carcinoma, followed by adjuvant stereotactic radiotherapy in the operative bed. Seven months after, she presented a local change in the irradiated area on the perfusion-weighted MRI, for which the differentiation between a local tumour recurrence and radionecrosis was not possible. PET with 2-deoxy-((18)F)-fluoro-D-glucose (FDG) revealed a hypermetabolic lesion. After surgical resection, the histological assessment has mainly recovered radionecrosis with few carcinoma cells. The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains.
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Neoplasias Encefálicas/cirugía , Traumatismos por Radiación/diagnóstico , Radiocirugia/efectos adversos , Adulto , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Carcinoma/patología , Carcinoma/secundario , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Traumatismos por Radiación/etiología , RadiofármacosRESUMEN
INTRODUCTION: Bilateral semicircular canal aplasia is extremely rare; discovery, when the cochlear-vestibular system is normal and there is no hearing loss, is serendipitous. CASE REPORT: Bilateral semicircular canal aplasia was serendipitously discovered in a 24-year-old male during assessment of unilateral mixed hearing loss with subnormal contralateral hearing. The deformity was isolated, with no associated syndrome. DISCUSSION/CONCLUSION: Incidence of this isolated entity is unknown, but doubtless greatly underestimated due to the absence of associated symptomatology. To the best of our knowledge, this is only the second report of bilateral aplasia of the entire semicircular canal system involving unilateral hearing loss. A review of the literature focuses on the embryological and molecular aspects.
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Canales Semicirculares/anomalías , Nervio Coclear/anomalías , Potenciales Evocados Auditivos , Perdida Auditiva Conductiva-Sensorineural Mixta/etiología , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Enfermedades Raras , Adulto JovenRESUMEN
OBJECTIVE: We ask whether Medicare's Hospital Compare random effects model correctly assesses acute myocardial infarction (AMI) hospital mortality rates when there is a volume-outcome relationship. DATA SOURCES/STUDY SETTING: Medicare claims on 208,157 AMI patients admitted in 3,629 acute care hospitals throughout the United States. STUDY DESIGN: We compared average-adjusted mortality using logistic regression with average adjusted mortality based on the Hospital Compare random effects model. We then fit random effects models with the same patient variables as in Medicare's Hospital Compare mortality model but also included terms for hospital Medicare AMI volume and another model that additionally included other hospital characteristics. PRINCIPAL FINDINGS: Hospital Compare's average adjusted mortality significantly underestimates average observed death rates in small volume hospitals. Placing hospital volume in the Hospital Compare model significantly improved predictions. CONCLUSIONS: The Hospital Compare random effects model underestimates the typically poorer performance of low-volume hospitals. Placing hospital volume in the Hospital Compare model, and possibly other important hospital characteristics, appears indicated when using a random effects model to predict outcomes. Care must be taken to insure the proper method of reporting such models, especially if hospital characteristics are included in the random effects model.
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Mortalidad Hospitalaria , Modelos Lineales , Modelos Logísticos , Medicare/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud/organización & administración , Admisión del Paciente/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Ocupación de Camas/estadística & datos numéricos , Sesgo , Investigación sobre Servicios de Salud , Capacidad de Camas en Hospitales/estadística & datos numéricos , Humanos , Formulario de Reclamación de Seguro/estadística & datos numéricos , Internet , Infarto del Miocardio/mortalidad , Valor Predictivo de las Pruebas , Ajuste de Riesgo , Estados Unidos/epidemiologíaAsunto(s)
Enflurano/farmacología , Ganglios Espinales/fisiología , Halotano/farmacología , Canales Iónicos/fisiología , Neuronas/fisiología , Ácido gamma-Aminobutírico/farmacología , Animales , Animales Recién Nacidos , Células Cultivadas , Potenciales Evocados/efectos de los fármacos , Canales Iónicos/efectos de los fármacos , Neuronas/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
The fast inactivation of sodium currents and the immobolization of sodium gating charge are thought to be closely coupled to each other. This notion was tested in the squid axon in which kinetics and steady-state properties of the gating charge movement were compared before and after removal of the Na inactivation by batrachotoxin (BTX), pronase, or chloramine-T. The immobilization of gating charge was determined by measuring the total charge movement (QON) obtained by integrating the ON gating current (Ig,ON) using a double pulse protocol. After removal of the fast inactivation with pronase or chloramine-T, the gating charge movement was no longer immobilized. In contrast, after BTX modification, the channels still exhibited an immobilization of the gating charge (QON) with an onset time course and voltage dependence similar to that for the activation process. These results show that BTX can uncouple the charge immobilization from the fast Na inactivation mechanism, suggesting that the Na gating charge movement can be immobilized independently of the inactivation of the channel.
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Axones/fisiología , Batracotoxinas/farmacología , Canales de Sodio/fisiología , Sodio/farmacología , Compuestos de Tosilo , Animales , Axones/efectos de los fármacos , Cloraminas/farmacología , Decapodiformes , Técnicas In Vitro , Cinética , Pronasa/farmacología , Valores de Referencia , Canales de Sodio/efectos de los fármacos , Tetrodotoxina/farmacologíaRESUMEN
Single cells from rat lacrimal glands were studied with the tight-seal whole-cell recording method. Ca-dependent K and Cl currents were measured in response to dialysis with inositoltrisphosphate or GTP gamma S, two compounds known for elevating internal Ca2+ concentration. The activation of the Ca-dependent currents elicited by either compound was partially inhibited by sustained depolarization or by removal of external Ca2+. Conversely, hyperpolarization or removal of external Mg2+ led to augmentations of the Ca-dependent currents. These effects became apparent about 1 min after initiation of cell dialysis with inositoltrisphosphate- or GTP gamma S-containing solutions, and they further developed during the ensuing 10 min. Holding potential and external divalent cations did not affect the Ca-dependent currents elicited by dialysing the cells with strongly buffered solutions containing 0.5 microM free Ca2+. In Ca2+-free external saline, cell currents were independent of the holding potential. It is suggested that InsP3 augments intracellular Ca2+ levels not only by releasing Ca2+ from internal stores but also by slowly increasing the Ca permeability of the plasma membrane. The results indicate that Ca2+ entry through the plasma membrane increases with hyperpolarization. The similarity of the effects seen in InsP3- and GTP gamma S-dialysed cells gives support to the hypothesis that production of the former depends on a GTP-binding protein.
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Calcio/farmacología , Glándulas Exocrinas/fisiología , Guanosina Trifosfato/análogos & derivados , Fosfatos de Inositol/farmacología , Fosfatos de Azúcar/farmacología , Tionucleótidos/farmacología , Animales , Cationes Bivalentes , Glándulas Exocrinas/efectos de los fármacos , Guanosina 5'-O-(3-Tiotrifosfato) , Guanosina Trifosfato/farmacología , Técnicas In Vitro , Inositol 1,4,5-Trifosfato , Cinética , Aparato Lagrimal/efectos de los fármacos , Aparato Lagrimal/fisiología , Magnesio/farmacología , Potenciales de la Membrana/efectos de los fármacos , RatasRESUMEN
The gating status of the QX-314 bound Na channels before and after suppressing the fast inactivation by chloramine-T (CT) was investigated by studying the gating charge immobilization using the OFF gating current (Ig,OFF). CT treatment, which abolishes the charge immobilization induced by a prolonged depolarization, altered the kinetics of Ig,OFF: the fast phase became insensitive to the pulse duration and the slow phase became three times faster than the control one. However, internally applied QX-314 (in the presence of external TTX) caused an immediate charge immobilization similar to that observed in the absence of CT treatment. The Ig,OFF exhibited kinetics similar to the inactivated channels, decaying with a very fast time course. We conclude that the charge immobilization is restored by QX-314 in the chloramine-T-treated axon and that the gating state of the QX-314-bound channel is similar to the inactivated one. The role of the gating charge immobilization in the use-dependent block mechanism is discussed.