RESUMEN
Karst aquifers are important sources of fresh water on a global scale. The hydrological modelling of karst spring discharge, however, still poses a challenge. In this study we apply a transfer function noise (TFN) model in combination with a bucket-type recharge model to simulate karst spring discharge. The application of the noise model for the residual series has the advantage that it is more consistent with assumptions for optimization such as homoscedasticity and independence. In an earlier hydrological modeling study, named Karst Modeling Challenge (KMC; Jeannin et al., J Hydrol 600:126-508, 2021), several modelling approaches were compared for the Milandre Karst System in Switzerland. This serves as a benchmark and we apply the TFN model to KMC data, subsequently comparing the results to other models. Using different data-model-combinations, the most promising data-model-combination is identified in a three-step least-squares calibration. To quantify uncertainty, the Bayesian approach of Markov-chain Monte Carlo (MCMC) sampling is subsequently used with uniform priors for the previously identified best data-model combination. The MCMC maximum likelihood solution is used to simulate spring discharge for a previously unseen testing period, indicating a superior performance compared to all other models in the KMC. It is found that the model gives a physically feasible representation of the system, which is supported by field measurements. While the TFN model simulated rising limbs and flood recession especially well, medium and baseflow conditions were not represented as accurately. The TFN approach poses a well-performing data-driven alternative to other approaches that should be considered in future studies.
RESUMEN
Rivers are the "tip of the iceberg", with the underlying groundwater being the unseen freshwater majority. Microbial community composition and the dynamics of shallow groundwater ecosystems are thus crucial, due to their potential impact on ecosystem processes and functioning. In early summer and late autumn, samples of river water from 14 stations and groundwater from 45 wells were analyzed along a 300 km transect of the Mur River valley, from the Austrian alps to the flats at the Slovenian border. The active and total prokaryotic communities were characterized using high-throughput gene amplicon sequencing. Key physico-chemical parameters and stress indicators were recorded. The dataset was used to challenge ecological concepts and assembly processes in shallow aquifers. The groundwater microbiome is analyzed regarding its composition, change with land use, and difference to the river. Community composition and species turnover differed significantly. At high altitudes, dispersal limitation was the main driver of groundwater community assembly, whereas in the lowland, homogeneous selection explained the larger share. Land use was a key determinant of the groundwater microbiome composition. The alpine region was more diverse and richer in prokaryotic taxa, with some early diverging archaeal lineages being highly abundant. This dataset shows a longitudinal change in prokaryotic communities that is dependent on regional differences affected by geomorphology and land use.
RESUMEN
SPG31 is a hereditary spastic paraplegia (HSP) caused by pathogenic variants in the REEP1 gene. The phenotype (SPG31) has occasionally been described with peripheral nervous system involvement, in additional to the gradually progressing lower limb spasticity that characterizes HSP. The objective of this study was to characterize patients with pathogenic REEP1 variants and neurophysiologically assess the extent of peripheral nerve involvement in this patient group. Thirty-eight index cases were molecular-genetically tested, yielding two previously reported pathogenic REEP1 variants and a novel missense variant, in a total of four index patients. Three of four probands and five additional family members underwent nerve conduction studies, electromyography, quantitative sensory testing, and examination of the autonomic nervous system. None of the examined patients had completely unremarkable results of peripheral nerve studies. Most showed electrophysiological signs of carpal tunnel syndrome, and one patient demonstrated a multifocal compression neuropathy. Autonomic testing revealed no severe dysfunction, and findings were limited to adrenergic function. HSP caused by pathogenic REEP1 variants may be accompanied by a generally mild and subclinical polyneuropathy with a predisposition to compression neuropathy, and should be considered in such cases.
Asunto(s)
Proteínas de Transporte de Membrana/genética , Conducción Nerviosa/fisiología , Polineuropatías , Paraplejía Espástica Hereditaria/genética , Adolescente , Adulto , Síndrome del Túnel Carpiano/etiología , Síndrome del Túnel Carpiano/fisiopatología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Polineuropatías/etiología , Polineuropatías/genética , Polineuropatías/fisiopatología , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/fisiopatología , Adulto JovenRESUMEN
A new method was developed and implemented into an Excel Visual Basic for Applications (VBAs) algorithm utilizing trigonometry laws in an innovative way to overlap recession segments of time series and create master recession curves (MRCs). Based on a trigonometry approach, the algorithm horizontally translates succeeding recession segments of time series, placing their vertex, that is, the highest recorded value of each recession segment, directly onto the appropriate connection line defined by measurement points of a preceding recession segment. The new method and algorithm continues the development of methods and algorithms for the generation of MRC, where the first published method was based on a multiple linear/nonlinear regression model approach (Posavec et al. 2006). The newly developed trigonometry-based method was tested on real case study examples and compared with the previously published multiple linear/nonlinear regression model-based method. The results show that in some cases, that is, for some time series, the trigonometry-based method creates narrower overlaps of the recession segments, resulting in higher coefficients of determination R2 , while in other cases the multiple linear/nonlinear regression model-based method remains superior. The Excel VBA algorithm for modeling MRC using the trigonometry approach is implemented into a spreadsheet tool (MRCTools v3.0 written by and available from Kristijan Posavec, Zagreb, Croatia) containing the previously published VBA algorithms for MRC generation and separation. All algorithms within the MRCTools v3.0 are open access and available free of charge, supporting the idea of running science on available, open, and free of charge software.
Asunto(s)
Algoritmos , Agua Subterránea , Dinámicas no Lineales , Programas InformáticosRESUMEN
Psychogenic non-epileptic seizures (PNES) are seizures which clinically resemble epileptic seizures but are without concurrent abnormal electrical charges. Though PNES can be just as serious and disabling as epileptic seizures, specific treatment guidelines are lacking, and different types of treatments are used. In this article we address the current research on psychotherapeutic treatment for PNES by discussing recent reviews and six randomized controlled trials (RCTs) on the subject. In conclusion, larger well-designed RCTs are needed in order to support the evidence for psychological interventions for this patient group.
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Trastornos Psicofisiológicos/terapia , Psicoterapia , Convulsiones/psicología , Humanos , Trastornos Psicofisiológicos/clasificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Convulsiones/clasificación , Convulsiones/terapiaRESUMEN
Karst aquifers represent dual flow systems consisting of a highly conductive conduit system embedded in a less permeable rock matrix. Hybrid models iteratively coupling both flow systems generally consume much time, especially because of the nonlinearity of turbulent conduit flow. To reduce calculation times compared to those of existing approaches, a new iterative equation solver for the conduit system is developed based on an approximated Newton-Raphson expression and a Gauß-Seidel or successive over-relaxation scheme with a single iteration step at the innermost level. It is implemented and tested in the research code CAVE but should be easily adaptable to similar models such as the Conduit Flow Process for MODFLOW-2005. It substantially reduces the computational effort as demonstrated by steady-state benchmark scenarios as well as by transient karst genesis simulations. Water balance errors are found to be acceptable in most of the test cases. However, the performance and accuracy may deteriorate under unfavorable conditions such as sudden, strong changes of the flow field at some stages of the karst genesis simulations.
Asunto(s)
Agua Subterránea , Movimientos del Agua , Benchmarking , Modelos TeóricosRESUMEN
A thorough data analysis combined with groundwater modelling was conducted in an Austrian binary karst aquifer to better understand changes in the hydrological behaviour observed at a karst spring. During a period of 4 years after a major flood event the spring hydrograph appears to be more damped with lower peak flow and higher baseflow than in the years before. The analysis of the hydrograph recession suggests that the observed hydrological change is caused by changes within the karst system rather than by varying hydro-meteorological conditions. The functioning of the aquifer and potential causes of the observed changes are further examined using the groundwater flow model MODFLOW. The simulation results suggest that a modification of hydraulic conductivity and storage within the conduit network, e.g. due to the plugging of the drainage conduits with sediments, may be the cause of the different behaviour. MODFLOW was able to reproduce the observed dynamics of spring flow, although it does not account for turbulent flow within karst conduits. Using a simplified model scenario it is demonstrated that the damping of the hydrograph is much stronger if turbulent conduit flow is taken into account. Thus, a turbulent flow model is needed to assess potential changes in the storage properties quantitatively.
RESUMEN
A new MODFLOW package (Nonlinear Flow Process; NLFP) simulating nonlinear flow following the Forchheimer equation was developed and implemented in MODLFOW-2005. The method is based on an iterative modification of the conductance calculated and used by MODFLOW to obtain an effective Forchheimer conductance. The package is compatible with the different layer types, boundary conditions, and solvers as well as the wetting capability of MODFLOW. The correct implementation is demonstrated using four different benchmark scenarios for which analytical solutions are available. A scenario considering transient flow in a more realistic setting and a larger model domain with a higher number of cells demonstrates that NLFP performs well under more complex conditions, although it converges moderately slower than the standard MODFLOW depending on the nonlinearity of flow. Thus, this new tool opens a field of opportunities to groundwater flow simulation with MODFLOW, especially for core sample simulation or vuggy karstified aquifers as well as for nonlinear flow in the vicinity of pumping wells.
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Agua Subterránea , Modelos Teóricos , Movimientos del Agua , Simulación por ComputadorRESUMEN
Measurements of cerebral blood flow (CBF) show large variability among healthy subjects. The aim of the present study was to investigate the relative effect of established factors influencing CBF on the variability of resting CBF. We retrospectively analyzed spontaneous variability in 430 CBF measurements acquired in 152 healthy, young subjects using (133)Xe single-photon emission computed tomography. Cerebral blood flow was correlated positively with both end-tidal expiratory PCO2 (PETCO2) and female gender and inversely with hematocrit (Hct). Between- and within-subject CO2 reactivity was not significantly different. Including PETCO2, Hct and gender in the model reduced between-subject and within-subject variance by 14% and 13.5%, respectively. Within-subject variability was mainly influenced by PETCO2 and between-subject variability mostly by Hct, whereas gender appeared to be of little added value when Hct was also accounted for. The present study confirms large between-subject variability in CBF measurements and that gender, Hct, and PETCO2 explain only a small part of this variability. This implies that a large fraction of CBF variability may be due to unknown factors such as differences in neuron density or metabolism that could be subject for further studies.
Asunto(s)
Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Tomografía Computarizada de Emisión de Fotón Único/métodos , Radioisótopos de Xenón , Adulto , Dióxido de Carbono/sangre , Femenino , Hematócrito , Humanos , Masculino , Descanso/fisiología , Estudios Retrospectivos , Adulto JovenRESUMEN
INVESTIGATION: Sodium nitroprusside (SNP) is a powerful vasodilatory agent that, similarly to glyceryl trinitrate (GTN), releases nitric oxide (NO) but in contrast does not pass the blood-brain barrier. Nevertheless, it has already been used in animal models without any knowledge of its headache-inducing potential. We hypothesized that SNP would induce headache and vasodilation of cephalic and radial but not cerebral arteries. METHODS: Five healthy volunteers received intravenous infusions of SNP in a non-randomized dose-titration (1-5 µg/kg/min) study. We recorded headache intensity (verbal rating scale from 0 to 10), velocity in the middle cerebral artery (VMCA), and diameters of the superficial temporal artery (STA) and radial artery (RA). RESULTS: All participants reported a dose-related headache (median peak = 2.5, range 0-3). SNP dilated the STA and RA, caused a marked increase of heart rate and a decrease of mean arterial pressure (MAP) and partial pressure of end-tidal carbon dioxide (PetCO2). We found that SNP decreased the velocity of the VMCA, but this was canceled by a decrease of cerebral blood flow (CBF) due to hypocapnia. CONCLUSION: The present study shows that SNP is a headache-inducing agent with close similarities to headaches induced by GTN and probably without effect on intracerebral arteries.
Asunto(s)
Circulación Cerebrovascular/efectos de los fármacos , Cefalea/inducido químicamente , Hemodinámica/efectos de los fármacos , Nitroprusiato/efectos adversos , Vasodilatadores/efectos adversos , Adulto , Presión Sanguínea/efectos de los fármacos , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Nitroprusiato/administración & dosificación , Vasodilatadores/administración & dosificación , Adulto JovenRESUMEN
Headache and facial pain are among the most common, disabling and costly disorders in Europe. Correct diagnosis and treatment is important for achieving a high quality of care. As a national organisation whose role is to educate and advocate for the needs of patients with primary headaches, the Danish Headache Society has set up a task force to develop a set of guidelines for the diagnosis, organisation and treatment of the most common types of headaches and for trigeminal neuralgia in Denmark. The guideline was published in Danish in 2010 and has been a great success. The Danish Headache Society decided to translate and publish our guideline in English to stimulate the discussion on optimal organisation and treatment of headache disorders and to encourage other national headache authorities to produce their own guidelines. The recommendations regarding the most common primary headaches and trigeminal neuralgia are largely in accordance with the European guidelines produced by the European Federation of Neurological Societies. The guideline provides a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organised in Denmark. This description is followed by individual sections on the characteristics, diagnosis, differential diagnosis and treatment of each of the major headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular problems regarding headache in children and headache in relation to female hormones and pregnancy are described.
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Neuralgia Facial/diagnóstico , Neuralgia Facial/terapia , Trastornos de Cefalalgia/diagnóstico , Trastornos de Cefalalgia/terapia , Analgesia/métodos , Analgesia/normas , Dinamarca , Humanos , Examen Neurológico/métodos , Examen Neurológico/normas , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/normas , Sociedades Médicas/normas , Neuralgia del Trigémino/diagnóstico , Neuralgia del Trigémino/terapiaRESUMEN
As a result of rock dissolution processes, karst aquifers exhibit highly conductive features such as caves and conduits. Within these structures, groundwater flow can become turbulent and therefore be described by nonlinear gradient functions. Some numerical groundwater flow models explicitly account for pipe hydraulics by coupling the continuum model with a pipe network that represents the conduit system. In contrast, the Conduit Flow Process Mode 2 (CFPM2) for MODFLOW-2005 approximates turbulent flow by reducing the hydraulic conductivity within the existing linear head gradient of the MODFLOW continuum model. This approach reduces the practical as well as numerical efforts for simulating turbulence. The original formulation was for large pore aquifers where the onset of turbulence is at low Reynolds numbers (1 to 100) and not for conduits or pipes. In addition, the existing code requires multiple time steps for convergence due to iterative adjustment of the hydraulic conductivity. Modifications to the existing CFPM2 were made by implementing a generalized power function with a user-defined exponent. This allows for matching turbulence in porous media or pipes and eliminates the time steps required for iterative adjustment of hydraulic conductivity. The modified CFPM2 successfully replicated simple benchmark test problems.
Asunto(s)
Agua Subterránea , Modelos Teóricos , Movimientos del Agua , Simulación por ComputadorRESUMEN
Experimental studies have shown that infusion of vasoactive neurotransmitters may trigger headache or migraine-like attacks in man. Pituitary adenylate cyclase activating peptide-38 (PACAP38) is a strong vasodilator found in trigeminal sensory and parasympathetic perivascular nerve fibers. We therefore hypothesized that infusion of PACAP38 would cause headache in healthy subjects and migraine-like attacks in migraine patients. Twelve healthy subjects and 12 migraine patients were examined in two separate studies. All subjects were allocated to receive 10 pmol/kg/min PACAP38 and placebo in a randomized, double-blind crossover study design. Headache was scored on a verbal rating scale (VRS) during hospital (0-2 h) and post-hospital (2-12 h) phases. Mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) by high resolution ultrasonography were recorded during hospital phase in migraineurs. PACAP38 infusion caused headache in all healthy subjects and 11 out of 12 migraine patients. Seven migraine patients experienced migraine-like attacks after PACAP38 and none after placebo (P = 0.016). Most of attacks (6 out of 7) occurred during the post-hospital phase [mean time 6 h (range 2-11)]. Two healthy subjects reported migraine-like attacks after PACAP38 during the hospital phase and none during the post-hospital phase. In the hospital phase, the area under the curve (AUC) for headache score was larger during PACAP38 infusion compared to placebo in healthy subjects (P = 0.005) and tended to be larger in migraineurs (P = 0.066). In the post-hospital phase, the AUC for headache was larger after PACAP38 infusion compared to placebo in both healthy subjects (P = 0.005) and migraine patients (P = 0.013). In migraine patients, PACAP38 caused a peak decrease of 16.1% in V(MCA) and a 37.5% increase in STA diameter at 20 min after start of infusion. In conclusion, PACAP38 infusion caused headache and vasodilatation in both healthy subjects and migraine patients. In migraine sufferers, PACAP38 caused delayed migraine-like attacks. The findings stimulate further investigation of the neuronal and vascular mechanisms of PACAP38.
Asunto(s)
Migraña sin Aura/inducido químicamente , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/toxicidad , Vasodilatadores/toxicidad , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Rubor/inducido químicamente , Cefalea/inducido químicamente , Cefalea/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/efectos de los fármacos , Arteria Cerebral Media/fisiopatología , Migraña sin Aura/fisiopatología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Arterias Temporales/diagnóstico por imagen , Arterias Temporales/efectos de los fármacos , Ultrasonografía , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Adulto JovenRESUMEN
PACAP38 is an endogenous peptide located in trigeminal perivascular nerve fibers in the brain. It reduces neuronal loss and infarct size in animal stroke models and has been proposed a candidate substance for human clinical studies of stroke. The effect on systemic hemodynamics and regional cerebral blood flow (rCBF) is not well understood. We here present the first study of the effect of PACAP38 on cerebral hemodynamics in humans. PACAP (10 pmol kg(-1) min(-1)) or placebo (0.9% saline) was infused for 20 min into 12 healthy young volunteers in a cross over, double blind study. rCBF was measured with SPECT and (133)Xe inhalation and mean blood flow velocity in the middle cerebral artery was measured with transcranial Doppler ultrasonography. End tidal partial pressure of CO(2) (P(et)CO(2)) and vital parameters were recorded throughout the 2 hour study period. PACAP38 decreased rCBF in all regions of interest (ROIs) by approximately 3-10%, though not uniformly significant. P(et)CO(2) decreased significantly during PACAP38 infusion compared to placebo (P=0.032), peak decrease was 8.9+/-3.8%. After correction for P(et)CO(2), rCBF remained unchanged in most ROIs. Heart rate increased 61.9+/-22.4% (P<0.0001 vs. placebo). These findings suggest that PACAP38 has no major direct effect on rCBF in healthy volunteers. The marked increase in heart rate and the reduction in rCBF caused by decreased P(et)CO(2) are important dose-limiting factors to consider in future clinical studies.
Asunto(s)
Circulación Cerebrovascular/efectos de los fármacos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Adolescente , Adulto , Circulación Cerebrovascular/fisiología , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inyecciones Intravenosas , Masculino , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/sangre , Valores de Referencia , Vasodilatadores/farmacologíaRESUMEN
A method to estimate reactive transport parameters as well as geometric conduit parameters from a multitracer test in a karst aquifer is provided. For this purpose, a calibration strategy was developed applying the two-region nonequilibrium model CXTFIT. The ambiguity of the model calibration was reduced by first calibrating the model with respect to conservative tracer breakthrough and later transferring conservative transport parameters to the reactive model calibration. The reactive transport parameters were only allowed to be within a defined sensible range to get reasonable calibration values. This calibration strategy was applied to breakthrough curves obtained from a large-scale multitracer test, which was performed in a karst aquifer of the Swabian Alb, Germany. The multitracer test was conducted by the simultaneous injection of uranine, sulforhodamine G, and tinopal CBS-X. The model succeeds to represent the tracer breakthrough curves (TBCs) of uranine and sulforhodamine G and verifies that tracer-rock interactions preferably occur in the immobile fluid region, although the fraction of this region amounts to only 3.5% of the total water. However, the model failed to account for the long tailing observed in the TBC of tinopal CBS-X. Sensitivity analyses reveal that model results for the conservative tracer transport are most sensitive to average velocity and volume fraction of the mobile fluid region, while dispersion and mass transfer coefficients are least influential. Consequently, reactive tracer calibration allows the determination of sorption sites in the mobile and immobile fluid region at small retardation coefficients.
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Agua Dulce/análisis , Movimientos del Agua , Abastecimiento de Agua/análisis , Calibración , Colorantes Fluorescentes/análisis , Colorantes Fluorescentes/química , Alemania , Modelos TeóricosRESUMEN
Ground water in karst terrains is highly vulnerable to contamination due to the rapid transport of contaminants through the highly conductive conduit system. For contamination risk assessment purposes, information about hydraulic and geometric characteristics of the conduits and their hydraulic interaction with the fissured porous rock is an important prerequisite. The relationship between aquifer characteristics and short-term responses to recharge events of both spring discharge and physicochemical parameters of the discharged water was examined using a process-based flow and transport model. In the respective software, a pipe-network model, representing fast conduit flow, is coupled to MODFLOW, which simulates flow in the fissured porous rock. This hybrid flow model was extended to include modules simulating heat and reactive solute transport in conduits. The application of this modeling tool demonstrates that variations of physicochemical parameters, such as solute concentration and water temperature, depend to a large extent on the intensity and duration of recharge events and provide information about the structure and geometry of the conduit system as well as about the interaction between conduits and fissured porous rock. Moreover, the responses of solute concentration and temperature of spring discharge appear to reflect different processes, thus complementing each other in the aquifer characterization.
Asunto(s)
Modelos Teóricos , Agua/análisis , Simulación por Computador , Sedimentos Geológicos , Porosidad , Temperatura , Factores de Tiempo , Agua/química , Movimientos del AguaRESUMEN
Sildenafil (Viagra), a selective inhibitor of phosphodiesterase 5 (PDE5), induces headache and migraine. Although previously supposed to be a "vascular" headache, no significant cerebral artery dilatation was found in vivo. Thus, we hypothesised that PDE5 may not be present or that sildenafil is less effective on the cGMP hydrolysis in cerebral arteries, and that sildenafil may not be an effective dilator of cerebral arteries under baseline conditions. We evaluated the presence of PDE5 mRNA and protein in human arteries. Furthermore, the effects of two selective PDE5 inhibitors, sildenafil and UK-114,542, and a PDE1 inhibitor UK-90,234 on cGMP hydrolysis were investigated in human and guinea pig cerebral arteries. The vasoactive responses of the compounds were evaluated in guinea pig basilar arteries in vitro, with concomitant measurements of cAMP and cGMP. PDE5 was found in human middle cerebral arteries. Sildenafil and UK-114,542 inhibited cGMP hydrolysis concentration-dependently in both species. In guinea pig arteries, sildenafil induced an endothelium-dependent vasodilatation only at concentrations above 10 nM, which was augmented by sodium nitroprusside and attenuated by reduction of cGMP, but was cGMP independent at high concentrations. UK-114,542 was more and UK-90,234 was less potent than sildenafil. In conclusion, PDE5 is present in human and guinea pig cerebral arteries, and is inhibited by sildenafil at micromolar levels. Sildenafil in vitro is a poor dilator of guinea pig cerebral arteries unless a nitric oxide donor is co-administered, corresponding to the previous findings in vivo.
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3',5'-GMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Arterias Cerebrales/efectos de los fármacos , Piperazinas/farmacología , 3',5'-GMP Cíclico Fosfodiesterasas/genética , 3',5'-GMP Cíclico Fosfodiesterasas/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Arteria Basilar/efectos de los fármacos , Arteria Basilar/enzimología , Arteria Basilar/fisiología , Western Blotting , Arterias Cerebrales/enzimología , Arterias Cerebrales/fisiología , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Guanilato Ciclasa/antagonistas & inhibidores , Cobayas , Humanos , Hidrólisis/efectos de los fármacos , Técnicas In Vitro , Lactante , Masculino , Morfolinas/farmacología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/enzimología , Nitroprusiato/farmacología , Oxadiazoles/farmacología , Purinas , Pirazoles/farmacología , Pirimidinas/farmacología , Pirimidinonas/farmacología , Quinoxalinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Citrato de Sildenafil , Sulfonas , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
A tracer test in a carbonate aquifer is analyzed using the method of moments and two analytical advection-dispersion models (ADMs) as well as a numerical model. The numerical model is a coupled continuum-pipe flow and transport model that accounts for two different flow components in karstified carbonate aquifers, i.e., rapid and often turbulent conduit flow and Darcian flow in the fissured porous rock. All techniques employed provide reasonable fits to the tracer breakthrough curve (TBC) measured at a spring. The resulting parameter estimates are compared to investigate how each conceptual model of flow and transport processes that forms the basis of the analyses affects the interpretation of the tracer test. Numerical modeling results suggest that the method of moments and the analytical ADMs tend to overestimate the conduit volume because part of the water discharged at the spring is wrongly attributed to the conduit system if flow in the fissured porous rock is ignored. In addition, numerical modeling suggests that mixing of the two flow components accounts for part of the dispersion apparent in the measured TBC, while the remaining part can be attributed to Taylor dispersion. These processes, however, cannot reasonably explain the tail of the TBC. Instead, retention in immobile-fluid regions as included in a nonequilibrium ADM provides a possible explanation.
Asunto(s)
Modelos Teóricos , Abastecimiento de Agua , Carbono , Monitoreo del Ambiente/métodos , Movimientos del AguaRESUMEN
BACKGROUND AND OBJECTIVE: Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine pathogenesis. BIBN4096BS is the first CGRP receptor antagonist available for human studies, and its efficacy in the acute treatment of migraine has been demonstrated. We investigated the ability of BIBN4096BS to inhibit human alphaCGRP (h-alphaCGRP)-induced headache and cerebral hemodynamic changes in healthy volunteers. METHODS: Ten healthy volunteers completed this double-blind, placebo-controlled crossover study with 2.5 mg BIBN4096BS and placebo as pretreatments before a 20-minute intravenous infusion of h-alphaCGRP (1.5 microg/min). Transcranial Doppler ultrasonography was used to measure blood flow velocity in the middle cerebral artery (MCA); regional and global cerebral blood flow (CBF) was measured by xenon 133 inhalation single-photon emission computed tomography. The temporal and radial artery diameter was measured by high-frequency ultrasound. Systemic hemodynamics, end-tidal partial pressure of carbon dioxide (PETCO(2)), and headache were monitored. RESULTS: Of the 10 volunteers, 6 had a CGRP-induced headache during the in-hospital phase after placebo pretreatment but none after BIBN4096BS (P = .031). BIBN4096BS did not affect changes in the diameter of the MCA or changes in CBF induced by h-alphaCGRP. Vasodilatation of the extracranial arteries was, however, significantly inhibited (P < .001 for temporal artery and P = .001 for radial artery). CONCLUSIONS: These results show that BIBN4096BS effectively prevents CGRP-induced headache and extracerebral vasodilatation but does not significantly affect the induced cerebral hemodynamic changes.
Asunto(s)
Arterias Cerebrales/fisiología , Cefalea/prevención & control , Piperazinas/farmacocinética , Quinazolinas/farmacocinética , Adulto , Péptido Relacionado con Gen de Calcitonina/análogos & derivados , Péptido Relacionado con Gen de Calcitonina/sangre , Péptido Relacionado con Gen de Calcitonina/farmacología , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina , Arterias Cerebrales/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Estudios Cruzados , Femenino , Cefalea/inducido químicamente , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Inyecciones Intravenosas , Masculino , Piperazinas/efectos adversos , Piperazinas/sangre , Quinazolinas/efectos adversos , Quinazolinas/sangre , Receptores de Péptido Relacionado con el Gen de Calcitonina/administración & dosificación , Receptores de Péptido Relacionado con el Gen de Calcitonina/uso terapéutico , Valores de Referencia , Tomógrafos Computarizados por Rayos X , Ultrasonografía Doppler Transcraneal/métodos , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
Spatial variations in hydraulic conductivity (K) can significantly affect the transport of contaminants in ground water. Conventional field methods, however, rarely provide a description of these variations at the level of detail necessary for reliable transport predictions and effective remediation designs. A direct-push (DP) method, hydrostratigraphic profiling, has been developed to characterize the spatial variability of both electrical conductivity (EC) and hydraulic conductivity in unconsolidated formations in a cost-effective manner. This method couples a dual-rod approach for performing slug tests in DP equipment with high-resolution EC logging. The method was evaluated at an extensively studied site in the Kansas River floodplain. A series of profiles was performed on a surface grid, resulting in a detailed depiction of the three-dimensional distribution of EC and K. Good agreement was found between K estimates obtained from this approach and those obtained using other methods. The results of the field evaluation indicate that DP hydrostratigraphic profiling is a promising method for obtaining detailed information about spatial variations in subsurface properties without the need for permanent wells.