RESUMEN
PURPOSE: To describe the origin of the vessels supplying the anterior sub-axial cervical vertebrae (C3-C7) to further understand their potential influence on anterior bone loss after anterior cervical spinal surgery. METHOD: Cadaveric dissection was performed on ten adult human necks after latex perfusion of their subclavian, common carotid and vertebral arteries. The nutrient vessels of the sub-axial cervical spine were identified and traced to their origin. The course and distribution of these vessels and their nutrient foraminae are described. RESULTS: In all cases the anterior nutrient vessels were derived from the thyro-cervical trunk with branches that passed over the longus coli muscles forming a leash of vessels in the pre-vertebral fascia which subsequently extended in a frond-like pattern to pass onto the anterior aspect of vertebrae. The more cranial the cervical level the fewer the number of nutrient vessels and foraminae. The distribution of the foraminae on the anterior vertebral body followed the oblique supero-medial course of the nutrient vessels. CONCLUSION: Nutrient vessels perforate the cervical vertebrae on their anterior surface. These are derived from a leash of vessels that lie within the pre-vertebral fascia overlying the longus coli muscles. The origin of these vessels is the ascending cervical artery with a variable contribution from the transverse cervical artery.
Asunto(s)
Vértebras Cervicales/irrigación sanguínea , Arteria Vertebral/anatomía & histología , Anciano , Anciano de 80 o más Años , Cadáver , HumanosRESUMEN
Deep neural networks (DNNs) provide state-of-the-art accuracy for vision tasks, but they require significant resources for training. Thus, they are trained on cloud servers far from the edge devices that acquire the data. This issue increases communication cost, runtime, and privacy concerns. In this study, a novel hierarchical training method for DNNs is proposed that uses early exits in a divided architecture between edge and cloud workers to reduce the communication cost, training runtime, and privacy concerns. The method proposes a brand-new use case for early exits to separate the backward pass of neural networks between the edge and the cloud during the training phase. We address the issues of most available methods that, due to the sequential nature of the training phase, cannot train the levels of hierarchy simultaneously or they do it with the cost of compromising privacy. In contrast, our method can use both edge and cloud workers simultaneously, does not share the raw input data with the cloud, and does not require communication during the backward pass. Several simulations and on-device experiments for different neural network architectures demonstrate the effectiveness of this method. It is shown that the proposed method reduces the training runtime for VGG-16 and ResNet-18 architectures by 29% and 61% in CIFAR-10 classification and by 25% and 81% in Tiny ImageNet classification, respectively, when the communication with the cloud is done over a low bit rate channel. This gain in the runtime is achieved, while the accuracy drop is negligible. This method is advantageous for online learning of high-accuracy DNNs on sensor-holding low-resource devices such as mobile phones or robots as a part of an edge-cloud system, making them more flexible in facing new tasks and classes of data.
RESUMEN
Learning probabilistic models that can estimate the density of a given set of samples, and generate samples from that density, is one of the fundamental challenges in unsupervised machine learning. We introduce a new generative model based on denoising density estimators (DDEs), which are scalar functions parametrized by neural networks, that are efficiently trained to represent kernel density estimators of the data. Leveraging DDEs, our main contribution is a novel technique to obtain generative models by minimizing the Kullback-Leibler (KL)-divergence directly. We prove that our algorithm for obtaining generative models is guaranteed to converge consistently to the correct solution. Our approach does not require specific network architecture as in normalizing flows (NFs), nor use ordinary differential equation (ODE) solvers as in continuous NFs. Experimental results demonstrate substantial improvement in density estimation and competitive performance in generative model training.
RESUMEN
An analytical model based on a modal expansion method is developed to investigate the optical transmission through metal gratings. This model gives analytical expressions for the transmission as well as for the dispersion relations of the modes responsible for high transmission. These expressions are accurate even for real metals used in the visible - near-infrared wavelength range, where surface plasmon polaritons (SPP's) are excited. The dispersion relations allow the nature of the modes to be assessed. We find that the transmission modes are hybrid between Fabry-Pérot like modes and SPP's. It is also shown that it is important to consider different refractive indices above and below the gratings in order to determine the nature of the hybrid modes. These findings are important as they clarify the nature of the modes responsible for high transmission. It can also be useful as a design tool for metal gratings for various applications.
Asunto(s)
Metales/química , Modelos Teóricos , Reconocimiento de Normas Patrones Automatizadas/métodos , Refractometría/instrumentación , Refractometría/métodos , Simulación por Computador , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.
Asunto(s)
COVID-19 , Vacunas , Atención Odontológica , Humanos , SARS-CoV-2 , Estudios Seroepidemiológicos , Reino Unido/epidemiologíaRESUMEN
Enhanced optical transmission (EOT) through a single aperture is usually achieved by exciting surface plasmon polaritons with periodic grooves. Surface plasmon polaritons are only excited by p-polarized incident light, i.e. with the electric field perpendicular to the direction of the grooves. The present study experimentally investigates EOT for s-polarized light. A subwavelength slit surrounded on each side by periodic grooves has been fabricated in a gold film and covered by a thin dielectric layer. The excitation of s-polarized dielectric waveguide modes inside the dielectric film strongly increases the s-polarized transmission. A 25 fold increase is measured as compared to the case without the dielectric film. Transmission measurements are compared with a coupled mode method and show good qualitative agreement. Adding a waveguide can improve light transmission through subwavelength apertures, as both s and p-polarization can be efficiently transmitted.
RESUMEN
In this paper, a fast and inexpensive wafer-scale process for the fabrication of arrays of nanoscale holes in thin gold films for plasmonics is shown. The process combines nanosphere lithography using spin-coated polystyrene beads with a sputter-etching process. This allows the batch fabrication of several 1000 microm(2) large hole arrays in 200 nm thick gold films without the use of an adhesion layer for the gold film. The hole size and lattice period can be tuned independently with this method. This allows tuning of the optical properties of the hole arrays for the desired application. An example application, refractive index sensing, is demonstrated.
RESUMEN
AIM: To determine the prevalence of Listeria monocytogenes and associated risk factors among beef operations (cow-calf and feedlot) in central and southern California. METHODS AND RESULTS: A repeated cross-sectional study where faecal and environmental samples were collected from 50 operations three times a year at different seasons was carried out. Samples were tested for presence of L. monocytogenes using a combination of enrichment and polymerase chain reaction tests. Data on putative risk factors were also collected. Listeria monocytogenes was detected in faecal samples from cows, calves and other animals on calf-cow operations at proportions of 3.1%, 3.75% and 2.5%, respectively. The organism was detected in 5.3% of cut-grass, 5.3% of soil, 14.3% of irrigation ditches, 3.1% of the ponds and 6.5% of water troughs samples. Listeria monocytogenes was less common in faecal (0.3%) and soil (0.75%) samples collected from feedlots. CONCLUSIONS: Listeria monocytogenes was present at a higher proportion among cow-calf operations than feedlots. There was no significant seasonal variation in the occurrence of this pathogen within the two types of operations. SIGNIFICANCE AND IMPACT OF THE STUDY: If risk mitigation strategies were implemented to reduce the public health risk these should focus in cow-calf operations.
Asunto(s)
Manipulación de Alimentos , Microbiología de Alimentos , Listeria monocytogenes , Listeriosis/prevención & control , Productos de la Carne/microbiología , Exposición Profesional/prevención & control , Animales , California , Bovinos , Humanos , Factores de RiesgoRESUMEN
The H,K-adenosine triphosphatase (ATPase) of gastric parietal cells is targeted to a regulated membrane compartment that fuses with the apical plasma membrane in response to secretagogue stimulation. Previous work has demonstrated that the alpha subunit of the H, K-ATPase encodes localization information responsible for this pump's apical distribution, whereas the beta subunit carries the signal responsible for the cessation of acid secretion through the retrieval of the pump from the surface to the regulated intracellular compartment. By analyzing the sorting behaviors of a number of chimeric pumps composed of complementary portions of the H, K-ATPase alpha subunit and the highly homologous Na,K-ATPase alpha subunit, we have identified a portion of the gastric H,K-ATPase, which is sufficient to redirect the normally basolateral Na,K-ATPase to the apical surface in transfected epithelial cells. This motif resides within the fourth of the H,K-ATPase alpha subunit's ten predicted transmembrane domains. Although interactions with glycosphingolipid-rich membrane domains have been proposed to play an important role in the targeting of several apical membrane proteins, the apically located chimeras are not found in detergent-insoluble complexes, which are typically enriched in glycosphingolipids. Furthermore, a chimera incorporating the Na, K-ATPase alpha subunit fourth transmembrane domain is apically targeted when both of its flanking sequences derive from H,K-ATPase sequence. These results provide the identification of a defined apical localization signal in a polytopic membrane transport protein, and suggest that this signal functions through conformational interactions between the fourth transmembrane spanning segment and its surrounding sequence domains.
Asunto(s)
Membrana Celular/enzimología , Polaridad Celular , ATPasa Intercambiadora de Hidrógeno-Potásio/análisis , ATPasa Intercambiadora de Hidrógeno-Potásio/química , Células Parietales Gástricas/enzimología , Señales de Clasificación de Proteína/fisiología , Secuencia de Aminoácidos , Animales , Transporte Biológico , Cationes/metabolismo , Línea Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Glicoesfingolípidos/metabolismo , Glicosilfosfatidilinositoles/metabolismo , ATPasa Intercambiadora de Hidrógeno-Potásio/genética , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Concentración de Iones de Hidrógeno , Proteínas de la Membrana/análisis , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Ouabaína/farmacología , Células Parietales Gástricas/citología , Células Parietales Gástricas/efectos de los fármacos , Células Parietales Gástricas/metabolismo , Señales de Clasificación de Proteína/química , Señales de Clasificación de Proteína/genética , Proteínas Recombinantes de Fusión/análisis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Alineación de Secuencia , Eliminación de Secuencia/genética , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/química , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Solubilidad , TransfecciónRESUMEN
We demonstrate high spectral control from surface emitting THz Quantum Cascade Lasers based on a two-dimensional photonic crystal cavity. The perforated top metallic contact acts as an in plane resonator in a tight double-metal plasmonic waveguide providing a strong optical feedback without needing three-dimensional cavity features. The optical far-field patterns do not exhibit the expected symmetry and the shape of the cavity mode. The difference is attributed to a metal surface plasmon mediated light outcoupling mechanism also responsible for the relatively low extraction efficiency.
Asunto(s)
Láseres de Semiconductores , Resonancia por Plasmón de Superficie/instrumentación , Cristalización/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Rayos Infrarrojos , FotonesRESUMEN
BACKGROUND: Cobalt chloride (CoCl2 ) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2 . OBJECTIVES: To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. ANIMALS: Five, healthy Standardbred mares. METHODS: Prospective, randomized, experimental dose-escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. RESULTS: All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60-126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291-300/163-213, 218-279). Hemodynamics normalized by 1-2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. CONCLUSIONS AND CLINICAL IMPORTANCE: The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns.
Asunto(s)
Cobalto/farmacología , Caballos , Hipertensión/veterinaria , Taquicardia/veterinaria , Administración Intravenosa , Hormona Adrenocorticotrópica/sangre , Animales , Cobalto/administración & dosificación , Cobalto/sangre , Cobalto/orina , Femenino , Hemodinámica/efectos de los fármacos , Hidrocortisona/sangre , Hipertensión/inducido químicamente , Proyectos Piloto , Estudios Prospectivos , Taquicardia/inducido químicamente , Troponina I/sangreRESUMEN
We combine photonic crystal and quantum cascade band engineering to create an in-plane laser at terahertz frequency. We demonstrate that such photonic crystal lasers strongly improve the performances of terahertz quantum cascade material in terms of threshold current, waveguide losses, emission mode selection, tunability and maximum operation temperature. The laser operates in a slow-light regime between the M saddle point and K band-edge in reciprocal lattice. Coarse frequency control of half of a terahertz is achieved by lithographically tuning the photonic crystal period. Thanks to field assisted gain shift and cavity pulling, the single mode emission is continuously tuned over 30 GHz.
RESUMEN
The in-vitro activity of telithromycin and comparator antibacterial agents was determined against clinical isolates of Legionella pneumophila collected in the PROTEKT surveillance study. In total, 133 isolates were collected between 1999 and 2004 from 13 countries (Australia, Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Portugal, Spain, Sweden and the USA). MICs were determined by broth microdilution. Telithromycin maintained activity between Year 1 (MIC(90) 0.015 mg/L) and Year 5 (MIC(90) 0.03 mg/L), as did the comparator antibacterial agents. Telithromycin appears to be a candidate for coverage of legionellosis in the empirical treatment of community-acquired respiratory tract infection.
Asunto(s)
Antibacterianos/farmacología , Infecciones Comunitarias Adquiridas/microbiología , Cetólidos/farmacología , Legionella pneumophila/efectos de los fármacos , Enfermedad de los Legionarios/microbiología , Infecciones del Sistema Respiratorio/microbiología , Adolescente , Adulto , Anciano , Infecciones Comunitarias Adquiridas/epidemiología , Femenino , Salud Global , Humanos , Legionella pneumophila/aislamiento & purificación , Enfermedad de los Legionarios/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Vigilancia de la Población , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
There are rare published reports of atrial fibrillation (AF) in foals, all of which are associated with structural heart disease or within the adaptive period of newborns. This report describes a 3-month-old Thoroughbred filly with AF and a structurally normal heart on echocardiography. Medical cardioversion of the foal's AF was attempted with three 20mg/kg doses of quinidine sulfate therapy without success. Timed, transcutaneous, direct current cardioversion was successfully performed using adhesive patches on the midthorax in conjunction with intravenous procainamide at a total dose of 20mg/kg. A normal sinus rhythm was maintained through discharge from the hospital and at recheck 5 months after cardioversion. Transcutaneous direct current cardioversion presents a feasible alternative to quinidine sulfate or transvenous electrical cardioversion in young or lower body weight equids.
Asunto(s)
Fibrilación Atrial/veterinaria , Cardioversión Eléctrica/veterinaria , Enfermedades de los Caballos/terapia , Animales , Fibrilación Atrial/terapia , CaballosRESUMEN
UNLABELLED: ESSENTIALS: We audited venous thromboembolism (VTE) in Achilles injuries after the use of prophylactic aspirin. We audited 218 patients with Achilles injury requiring lower limb immobilization for ≥ 1 week. Fourteen patients (6.4%, 95% CI 3.6% to 10.5%) developed symptomatic and confirmed VTE. The incidence was similar to the 6.3% identified in the same patient group prior to the use of aspirin. BACKGROUND/OBJECTIVE: We report a follow-up audit of the incidence of venous thromboembolism (VTE) in patients requiring lower limb immobilization because of Achilles tendon injury, since the introduction of a policy to routinely prescribe 100 mg of aspirin daily. PATIENTS/METHODS: We studied 218 patients aged 18-65 years who attended the Orthopaedic Assessment Unit at Wellington Hospital between January 2013 and December 2014 with Achilles tendon injury requiring lower limb immobilization for ≥ 1 week. Information on assessment of VTE risk, prescription of aspirin and symptomatic VTE occurring within 70 days of immobilization was obtained and compared with the same information collected with the same method in the same patient group between January 2006 and December 2007, before the policy to routinely prescribe aspirin was introduced. RESULTS: A total of 189 of 218 (93%) patients were prescribed aspirin, as compared with 0.5% previously. Fourteen patients (6.4%, 95% confidence interval 3.6-10.5%) developed symptomatic radiologically confirmed VTE (10 distal deep vein thromboses [DVTs], two proximal DVTs, one pulmonary embolism [PE], and one PE with distal DVT). Aspirin was prescribed to all patients who subsequently developed a VTE; in one of 14, a recognized risk factor was documented. The VTE incidence was similar to the 6.3% identified in the previous audit. CONCLUSION: Lower limb immobilization following Achilles tendon injury confers a high risk of VTE even with aspirin prophylaxis. Consideration should be given to prophylaxis with low molecular weight heparin during lower limb immobilization following Achilles tendon injury, as this has proven efficacy in this clinical situation.
Asunto(s)
Tendón Calcáneo/lesiones , Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Embolia Pulmonar/prevención & control , Restricción Física/efectos adversos , Traumatismos de los Tendones/terapia , Tromboembolia Venosa/prevención & control , Trombosis de la Vena/prevención & control , Adolescente , Adulto , Anciano , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/epidemiología , Factores de Riesgo , Traumatismos de los Tendones/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Several tests have been evaluated in horses for quantifying insulin dysregulation to support a diagnosis of equine metabolic syndrome. Comparing the performance of these tests in the same horses will provide clarification of their accuracy in the diagnosis of equine insulin dysregulation. OBJECTIVES: The aim of this study was to evaluate the agreement between basal serum insulin concentrations (BIC), the oral sugar test (OST), the combined glucose-insulin test (CGIT), and the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGTT). ANIMALS: Twelve healthy, light-breed horses. METHODS: Randomized, prospective study. Each of the above tests was performed on 12 horses. RESULTS: Minimal model analysis of the FSIGTT was considered the reference standard and classified 7 horses as insulin resistant (IR) and 5 as insulin sensitive (IS). In contrast, BIC and OST assessment using conventional cut-off values classified all horses as IS. Kappa coefficients, measuring agreement among BIC, OST, CGIT, and FSIGTT were poor to fair. Sensitivity of the CGIT (positive phase duration of the glucose curve >45 minutes) was 85.7% and specificity was 40%, whereas CGIT ([insulin]45 >100 µIU/mL) sensitivity and specificity were 28.5% and 100%, respectively. Area under the glucose curve (AUCg0-120 ) was significantly correlated among the OST, CGIT, and FSIGTT, but Bland-Altman method and Lin's concordance coefficient showed a lack of agreement. CONCLUSIONS: Current criteria for diagnosis of insulin resistance using BIC and the OST are highly specific but lack sensitivity. The CGIT displayed better sensitivity and specificity, but modifications may be necessary to improve agreement with minimal model analysis.
Asunto(s)
Glucemia/análisis , Enfermedades de los Caballos/diagnóstico , Resistencia a la Insulina , Insulina/sangre , Animales , Femenino , Prueba de Tolerancia a la Glucosa/veterinaria , Enfermedades de los Caballos/metabolismo , Caballos , Masculino , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
We designed, fabricated and characterised electrically injected quantum cascade lasers with photonic crystal reflectors emitting at terahertz frequencies (3.75 THz). These in-plane emitting structures display typical threshold current densities of 420 A/cm2 and output powers of up to 2 mW under pulsed excitation. The emission characteristics are shown to be robust, as with increasing current the emission remains singlemode with no drift in wavelength, this results from the narrow reflectivity band of the photonic crystal reflectors.
RESUMEN
This was a multicenter, randomized, double-blind, placebo-controlled pilot study, evaluating the safety and efficacy of a standard care treatment regimen with the addition of either nesiritide or placebo (SCP) in 237 Emergency Department (ED)/Observation Unit (OU) patients with decompensated heart failure (HF). Efficacy measures included initial admission, length of hospital stay (LOS), and inpatient rehospitalization through 30 days. Compared to the standard care group, patients who also received nesiritide had 11% fewer inpatient hospital admissions at the index ED visit (55% SCP, 49% nesiritide, p = 0.436), and 57% fewer inpatient hospitalizations within 30 days after discharge from the index hospitalization (23% SCP, 10% nesiritide, p = 0.058). The duration of rehospitalization was shorter for nesiritide patients (median LOS 2.5 vs. 6.5 days, p = 0.032). The incidence of symptomatic hypotension was low and did not differ between the groups. This study showed that nesiritide is safe when used in the emergency department, observation units, or similar settings.
Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Disnea/tratamiento farmacológico , Servicio de Urgencia en Hospital , Femenino , Costos de Hospital , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Natriuréticos/administración & dosificación , Natriuréticos/efectos adversos , Péptido Natriurético Encefálico/administración & dosificación , Péptido Natriurético Encefálico/efectos adversos , Proyectos PilotoRESUMEN
The physiologic function of an ion pump is determined, in part, by its subcellular localization and by the cellular mechanisms that modulate its activity. The Na,K-ATPase and the gastric H,K-ATPase are two closely related members of the P-type family of ion transporting ATPases. Despite their homology, these pumps are sorted to different domains in polarized epithelial cells and their enzymatic activities are subject to distinct regulatory pathways. The molecular signals responsible for these properties have begun to be elucidated. It appears that a complex array of inter- and intra-molecular interactions govern these proteins' trafficking, distribution and catalytic capacity.
Asunto(s)
Bombas Iónicas/metabolismo , Transporte de Proteínas/fisiología , Animales , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Polaridad Celular/fisiología , Células Epiteliales/metabolismo , Células Epiteliales/ultraestructura , Mucosa Gástrica/metabolismo , ATPasa Intercambiadora de Hidrógeno-Potásio/química , ATPasa Intercambiadora de Hidrógeno-Potásio/genética , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Humanos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estructura Terciaria de Proteína/fisiología , Transducción de Señal/fisiología , ATPasa Intercambiadora de Sodio-Potasio/química , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Estómago/ultraestructuraRESUMEN
Several members of the H+,K+-ATPase family of ion pumps participate in renal K transport. This class of P-type ATPases includes the gastric H+,K+-ATPase as well as a number of nongastric H+,K+-ATPase isoforms. Physiological studies suggest that these enzymes operate predominantly at the apical surfaces of tubule epithelial cells. Although much has been learned about the pattern of H+,K+-ATPase isoform expression and its response to stress, the functional and cell biologic attributes of these pumps remain largely unelucidated. We have studied the properties of renal H+,K+-ATPases both in vitro and in situ. Our analysis of ion fluxes driven by a nongastric H+,K+-ATPase isoform suggests that it exchanges Na (rather than H) for K under normal circumstances. Thus, the individual H+,K+-ATPase isoforms may make diverse contributions to renal cation transport. We find that the activities of renal H+,K+-ATPases in situ are regulated by endocytosis, which is mediated by an endocytosis signal in the cytoplasmic tail of the gastric H+,K+-ATPase beta-subunit. Transgenic mice expressing a version of this protein in which the signal has been disabled show constitutively active renal K resorption. The identities of the H+,K+-ATPase isoforms that are normally subject to endocytic regulation and the nature of the participating epithelial cell machinery have yet to be established.