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1.
Chemistry ; 29(3): e202202833, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36217899

RESUMEN

The [2+2] cycloaddition - retro-electrocyclization (CA-RE) reaction is a "click-like" protocol for facile synthesis of donor-acceptor chromophores from an alkyne and tetracyanoethylene. Herein we shed light on the mechanism of this reaction by detailed kinetics studies using 1 H NMR spectroscopy. By considering several experiments simultaneously, a variety of mechanistic models was evaluated. Surprisingly, a model in which the final 1,1,4,4-tetracyanobuta-1,3-diene product promoted the first step was the only one that described well the experimental data. This autocatalysis model also involved a non-concerted, stepwise formation of the cyclobutene cycloaddition adduct. By proper choice of conditions, we were able to generate the transient cyclobutene in sufficient amount to verify it as an intermediate using 13 C NMR spectroscopy. For its final retro-electrocyclization step, simple first-order kinetics was observed and only minor solvent dependence, which indicates a concerted reaction.


Asunto(s)
Alquinos , Reacción de Cicloadición , Alquinos/química , Espectroscopía de Resonancia Magnética , Ciclización
2.
Pflugers Arch ; 471(2): 271-283, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30219946

RESUMEN

Resistance vessels regulate blood flow by continuously adjusting activity of the wall smooth muscle cells. These cells integrate a variety of stimuli from blood, endothelium, autonomic nerves, and surrounding tissues. Each stimulus elicits an intracellular signaling cascade that eventually influences activation of the contractile machinery. The characteristic time scale of each cascade and the sharing of specific reactions between cascades provide for complex behavior when a vessel receives multiple stimuli. Here, we apply sequential stimulation with invariant concentrations of vasoconstrictor (norepinephrine/methoxamine) and vasodilator (SNAP/carbacol) to rat mesenteric vessels in the wire myograph to show that (1) time elapsed between addition of two vasoactive drugs and (2) the sequence of addition may significantly affect final force development. Furthermore, force oscillations (vasomotion) often appear upon norepinephrine administration. Using computational modeling in combination with nitric oxide (NO) inhibition/NO addition experiments, we show that (3) amplitude and number of oscillating vessels increase over time, (4) the ability of NO to induce vasomotion depends on whether it is applied before or after norepinephrine, and (5) emergence of vasomotion depends on the prior dynamical state of the system; in simulations, this phenomenon appears as "hysteresis." These findings underscore the time-dependent nature of vascular tone generation which must be considered when evaluating the vasomotor effects of multiple, simultaneous stimuli in vitro or in vivo.


Asunto(s)
Arterias Mesentéricas/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Sistema Vasomotor/efectos de los fármacos , Animales , Masculino , Arterias Mesentéricas/metabolismo , Mesenterio/efectos de los fármacos , Mesenterio/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Norepinefrina/farmacología , Ratas , Ratas Sprague-Dawley , Resistencia Vascular/efectos de los fármacos , Sistema Vasomotor/metabolismo
3.
Br J Neurosurg ; 31(4): 452-458, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27626705

RESUMEN

BACKGROUND: We have previously suggested that surgical gloves could be a possible means for transferring microorganisms from skin flora to shunt material during surgery. The objectives of this study were to examine (1) whether the rate of shunt infections was reduced after introducing intraoperative glove change before handling the shunt material; (2) clinical presentation of shunt infections, microbiological data, and treatment management; and (3) predictors of shunt infections. METHODS: A retrospective study of 432 shunt operations in 295 adults was undertaken over a 7-year period. Study population consisted of two groups: Group A without intraoperative glove change (2003-2006), and Group B with change of the outer pair of the initial double gloves before handling the shunt material (2006-2009). The results were compared at 6- and 12-month postoperatively. A binary logistic regression was performed to determine predictors of shunt infections. RESULTS: Overall, 46 (10.6%) infection episodes occurred in 40 (13.6%) patients. Main symptoms were fever, abdominal pain and altered mental status. Propionibacterium acnes was the frequently isolated microorganism, followed by Staphylococcus species. The infection rate was reduced only moderately from 11.8% in Group A to 9.8% in Group B (p = .472). Patients with subarachnoid haemorrhage were more likely to experience shunt infections (17.9%), compared to patients with normal pressure hydrocephalus (5.9%). An increased likelihood of shunt infections for the increased number of subsequent shunt revisions (p = .030) and a trend towards prior history of shunt infections (p = .118) was seen. After adjusting for various covariates, a decreased likelihood of shunt infections for intraoperative glove change was seen at 6-month follow-up for first-time shunt insertion (p = .050). CONCLUSION: Intraoperative glove change does not significantly reduce the risk of shunt infection. However, it seems to reduce the infection rate within 6 months in patients undergoing first-time shunt insertion only.


Asunto(s)
Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Guantes Quirúrgicos , Infecciones Relacionadas con Prótesis/líquido cefalorraquídeo , Infecciones Relacionadas con Prótesis/prevención & control , Infección de la Herida Quirúrgica/líquido cefalorraquídeo , Infección de la Herida Quirúrgica/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hidrocefalia/cirugía , Incidencia , Masculino , Persona de Mediana Edad , Propionibacterium acnes , Infecciones Relacionadas con Prótesis/microbiología , Estudios Retrospectivos , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Infección de la Herida Quirúrgica/microbiología , Adulto Joven
4.
Perfusion ; 32(3): 192-199, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28327077

RESUMEN

BACKGROUND: Muscle tissue saturation (StO2) measured with near-infrared spectroscopy has generally been considered a measurement of the tissue microcirculatory condition. However, we hypothesized that StO2 could be more regarded as a fast and reliable measure of global than of regional circulatory adequacy and tested this with muscle, intestinal and brain metabolomics at normal and two levels of low cardiopulmonary bypass blood flow rates in a porcine model. METHODS: Twelve 80 kg pigs were connected to normothermic cardiopulmonary bypass with a blood flow of 60 mL/kg/min for one hour, reduced randomly to 47.5 mL/kg/min (Group I) or 35 mL/kg/min (Group II) for one hour followed by one hour of 60 mL/kg/min in both groups. Regional StO2 was measured continuously above the musculus gracilis (non-cannulated leg). Metabolomics were obtained by brain tissue oxygen monitoring system (Licox) measurements of the brain and microdialysis perfusate from the muscle, intestinal mucosa and brain. A non-parametric statistical method was used. RESULTS: The systemic parameters showed profound systemic ischaemia during low CPB blood flow. StO2 did not change markedly in Group I, but in Group II, StO2 decreased immediately when blood flow was reduced and, furthermore, was not restored despite blood flow being normalized. Changes in the metabolomics from the muscle, colon and brain followed the changes in StO2. CONCLUSION: We found, in this experimental cardiopulmonary bypass model, that StO2 reacted rapidly when the systemic circulation became inadequate and, furthermore, reliably indicate insufficient global tissue perfusion even when the systemic circulation was restored after a period of systemic hypoperfusion.


Asunto(s)
Encéfalo/irrigación sanguínea , Puente Cardiopulmonar , Hemodinámica , Mucosa Intestinal/irrigación sanguínea , Metabolómica , Músculo Esquelético/irrigación sanguínea , Oxígeno/sangre , Animales , Encéfalo/metabolismo , Circulación Cerebrovascular , Femenino , Mucosa Intestinal/metabolismo , Metabolómica/métodos , Microcirculación , Músculo Esquelético/metabolismo , Oxígeno/metabolismo , Consumo de Oxígeno , Distribución Aleatoria , Flujo Sanguíneo Regional , Espectroscopía Infrarroja Corta , Porcinos
5.
Acta Radiol ; 57(1): 82-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25523064

RESUMEN

BACKGROUND: Clinical functional magnetic resonance imaging (fMRI) is still an upcoming diagnostic tool because it is time-consuming to perform the post-scan calculations and interpretations. A standardized and easily used method for the clinical assessment of fMRI scans could decrease the workload and make fMRI more attractive for clinical use. PURPOSE: To evaluate a standardized clinical approach for distance measurement between benign brain tumors and eloquent cortex in terms of the ability to predict pre- and postoperative neurological deficits after intraoperative neuronavigation-assisted surgery. MATERIAL AND METHODS: A retrospective study of 34 patients. The fMRI data were reanalyzed using a standardized distance measurement procedure combining data from both fMRI and three-dimensional T1 MRI scans. The pre- and postoperative neurological status of each patient was obtained from hospital records. Data analysis was performed using logistic regression analysis to determine whether the distance measured between the tumor margin and fMRI activity could serve as a predictor for neurological deficits. RESULTS: An odds ratio of 0.89 mm(-1) (P = 0.03) was found between the risk of preoperative neurological motor deficits and the tumor-fMRI distance. An odds ratio of 0.82 mm(-1) (P = 0.04) was found between the risk of additional postoperative neurological motor deficits and the tumor-fMRI distance. The tumor was radically removed in 10 cases; five patients experienced additional postoperative motor deficits (tumor-fMRI distance <18 mm) and five did not (tumor-fMRI distance >18 mm) (P = 0.008). CONCLUSION: This study indicates that the distance measured between the tumor margin and fMRI activation could serve as a valuable predictor of neurological motor deficits.


Asunto(s)
Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodos , Periodo Preoperatorio , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/cirugía , Niño , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos
6.
Bioinformatics ; 29(10): 1292-8, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23505296

RESUMEN

MOTIVATION: Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredictable. In heterogeneous populations, synchronization of events becomes a cardinal problem-particularly for phase coherence in oscillating systems. RESULTS: The present article presents a novel strategy for construction of large-scale simulation programs of heterogeneous biological entities. The strategy is designed to be tractable, to handle heterogeneity and to handle computational cost issues simultaneously, primarily by writing a generator of the 'model to be simulated'. We apply the strategy to model glycolytic oscillations among thousands of yeast cells coupled through the extracellular medium. The usefulness is illustrated through (i) benchmarking, showing an almost linear relationship between model size and run time, and (ii) analysis of the resulting simulations, showing that contrary to the experimental situation, synchronous oscillations are surprisingly hard to achieve, underpinning the need for tools to study heterogeneity. Thus, we present an efficient strategy to model the biological heterogeneity, neglected by ordinary mean-field models. This tool is well posed to facilitate the elucidation of the physiologically vital problem of synchronization. AVAILABILITY: The complete python code is available as Supplementary Information. CONTACT: bjornhald@gmail.com or pgs@kiku.dk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Simulación por Computador , Modelos Biológicos , Levaduras/metabolismo , Glucólisis , Lenguajes de Programación , Programas Informáticos
7.
Acta Oncol ; 52(7): 1314-9, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23981047

RESUMEN

INTRODUCTION: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. MATERIAL AND METHODS: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on isocurves from Eclipse. Data was analysed by t-test. Estimates are given with 95% CI. RESULTS: A mean ADC difference of 4.6(0.3;8.9)× 10(-5) mm(2)/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60)× 10(-5) mm(2)/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58)× 10(-5) mm(2)/s, p = 0.29; 15 Gy; 5.81(1.53;10.11)× 10(-5) mm(2)/s, p = 0.01; 25 Gy; 5.80(2.43;9.18)× 10(-5) mm(2)/s, p = 0.002; 35 Gy; 5.93(2.89;8.97)× 10(-5) mm(2)/s, p = 0.0007; 45 Gy; 4.32(-0.24;8.89)× 10(-5) mm(2)/s, p = 0.06; 55 Gy; -4.04(-14.96;6.89)× 10(-5) mm(2)/s, p = 0.39. CONCLUSION: The results indicate that the structural integrity of white matter, assessed by ADC-values based on DTI, undergoes changes after radiation therapy starting as early as total dose levels between 5 and 15 Gy.


Asunto(s)
Biomarcadores/análisis , Encéfalo/patología , Imagen de Difusión Tensora , Leucoencefalopatías/diagnóstico , Traumatismos por Radiación/diagnóstico , Neoplasias Supratentoriales/diagnóstico , Adulto , Anciano , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/radioterapia , Femenino , Humanos , Leucoencefalopatías/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Traumatismos por Radiación/prevención & control , Neoplasias Supratentoriales/etiología
8.
Biophys J ; 102(6): 1352-62, 2012 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-22455918

RESUMEN

Conduction processes in the vasculature have traditionally been described using cable theory, i.e., locally induced signals decaying passively along the arteriolar wall. The decay is typically quantified using the steady-state length-constant, λ, derived from cable theory. However, the applicability of cable theory to blood vessels depends on assumptions that are not necessarily fulfilled in small arteries and arterioles. We have employed a morphologically and electrophysiologically detailed mathematical model of a rat mesenteric arteriole to investigate if the assumptions hold and whether λ adequately describes simulated conduction profiles. We find that several important cable theory assumptions are violated when applied to small blood vessels. However, the phenomenological use of a length-constant from a single exponential function is a good measure of conduction length. Hence, λ should be interpreted as a descriptive measure and not in light of cable theory. Determination of λ using cable theory assumes steady-state conditions. In contrast, using the model it is possible to probe how conduction behaves before steady state is achieved. As ion channels have time-dependent activation and inactivation, the conduction profile changes considerably during this dynamic period with an initially longer spread of current. This may have implications in relation to explaining why different agonists have different conduction properties. Also, it illustrates the necessity of using and developing models that handle the nonlinearity of ion channels.


Asunto(s)
Arteriolas/fisiología , Fenómenos Electrofisiológicos/fisiología , Modelos Biológicos , Animales , Simulación por Computador , Impedancia Eléctrica , Cinética , Membranas/fisiología , Ratas
9.
Pflugers Arch ; 463(2): 279-95, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22052159

RESUMEN

Intracellular Ca(2+) signals underlying conducted vasoconstriction to local application of a brief depolarizing KCl stimulus was investigated in rat mesenteric terminal arterioles (<40 µm). Using a computer model of an arteriole segment comprised of coupled endothelial cells (EC) and vascular smooth muscle cells (VSMC) simulations of both membrane potential and intracellular [Ca(2+)] were performed. The "characteristic" length constant, λ, was approximated using a modified cable equation in both experiments and simulations. We hypothesized that K(+) conductance in the arteriolar wall limit the electrotonic spread of a local depolarization along arterioles by current dissipation across the VSMC plasma membrane. Thus, we anticipated an increased λ by inhibition of voltage-activated K(+) channels. Application of the BK(Ca) channel blocker iberiotoxin (100 nM) onto mesenteric arterioles in vitro and inhibition of BK(Ca) channel current in silico increased λ by 34% and 32%, respectively. Similarly, inhibition of K(V) channels in vitro (4-aminopyridine, 1 mM) or in silico increased λ by 41% and 21%, respectively. Immunofluorescence microscopy demonstrated expression of BK(Ca), Kv1.5, Kv2.1, but not Kv1.2, in VSMCs of rat mesenteric terminal arterioles. Our results demonstrate that inhibition of voltage-activated K(+) channels enhance vascular-conducted responses to local depolarization in terminal arterioles by increasing the membrane resistance of VSMCs. These data contribute to our understanding of how differential expression patterns of voltage-activated K(+) channels may influence conducted vasoconstriction in small arteriolar networks. This finding is potentially relevant to understanding the compromised microcirculatory blood flow in systemic vascular diseases such as diabetes mellitus and hypertension.


Asunto(s)
Arteriolas/fisiología , Canal de Potasio Kv1.5/fisiología , Arterias Mesentéricas/fisiología , Canales de Potasio/fisiología , Canales de Potasio Shab/fisiología , Sistema Vasomotor/fisiología , Animales , Calcio/metabolismo , Simulación por Computador , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio , Masculino , Potenciales de la Membrana/fisiología , Modelos Animales , Modelos Teóricos , Músculo Liso Vascular/fisiología , Ratas , Ratas Sprague-Dawley
10.
Biophys J ; 99(10): 3191-9, 2010 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-21081066

RESUMEN

Glycolytic oscillations in a stirred suspension of starved yeast cells is an excellent model system for studying the dynamics of metabolic switching in living systems. In an open-flow system the oscillations can be maintained indefinitely at a constant operating point where they can be characterized quantitatively by experimental quenching and bifurcation analysis. In this article, we use these methods to show that the dynamics of oscillations in a closed system is a simple transient version of the open-system dynamics. Thus, easy-setup closed-system experiments are also useful for investigations of central metabolism dynamics of yeast cells. We have previously proposed a model for the open system comprised of the primary fermentative reactions in yeast that quantitatively describes the oscillatory dynamics. However, this model fails to describe the transient behavior of metabolic switching in a closed-system experiment by feeding the yeast suspension with a glucose pulse-notably the initial NADH spike and final NADH rise. Another object of this study is to gain insight into the secondary low-flux metabolic pathways by feeding starved yeast cells with various metabolites. Experimental and computational results strongly suggest that regulation of acetaldehyde explains the observed behavior. We have extended the original model with regulation of pyruvate decarboxylase, a reversible alcohol dehydrogenase, and drainage of pyruvate. Using the method of time rescaling in the extended model, the description of the transient closed-system experiments is significantly improved.


Asunto(s)
Glucólisis , Modelos Biológicos , Saccharomyces cerevisiae/metabolismo , Acetaldehído/farmacología , Acetatos/farmacología , Biomasa , Simulación por Computador , Cianuros/farmacología , Etanol/farmacología , Fluorescencia , Glucosa/farmacología , Glucólisis/efectos de los fármacos , NADP/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/efectos de los fármacos , Factores de Tiempo
11.
Proc Natl Acad Sci U S A ; 104(47): 18377-81, 2007 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-18003917

RESUMEN

Mutual synchronization by exchange of chemicals is a mechanism for the emergence of collective dynamics in cellular populations. General theories exist on the transition to coherence, but no quantitative, experimental demonstration has been given. Here, we present a modeling and experimental analysis of cell-density-dependent glycolytic oscillations in yeast. We study the disappearance of oscillations at low cell density and show that this phenomenon occurs synchronously in all cells and not by desynchronization, as previously expected. This study identifies a general scenario for the emergence of collective cellular oscillations and suggests a quorum-sensing mechanism by which the cell density information is encoded in the intracellular dynamical state.


Asunto(s)
Percepción de Quorum , Saccharomyces cerevisiae/citología , Recuento de Colonia Microbiana , Simulación por Computador , Glucólisis , Modelos Biológicos , Saccharomyces cerevisiae/metabolismo
12.
Ugeskr Laeger ; 180(26)2018 Jun 25.
Artículo en Danés | MEDLINE | ID: mdl-29938638

RESUMEN

Death can be pronounced on both circulatory and brain criteria. In both cases, irreversible loss of brain function is essential in understanding finale death, as irreversible loss of breathing - a brainstem function - is mandatory. Brain function ceases irreversibly as a consequence of lack of blood supply to the brain, caused by circulatory arrest or by raised intracranial pressure. Brain function is central in death, which must be reflected in a future death criterion, stated in WHO´s new death criterion based on irreversible loss of capacity for consciousness and loss of brainstem function.


Asunto(s)
Muerte Encefálica/clasificación , Muerte , Tronco Encefálico , Humanos
13.
FEBS J ; 272(11): 2648-60, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15943800

RESUMEN

This work concerns the cause of glycolytic oscillations in yeast. We analyse experimental data as well as models in two distinct cases: the relaxation-like oscillations seen in yeast extracts, and the sinusoidal Hopf oscillations seen in intact yeast cells. In the case of yeast extracts, we use flux-change plots and model analyses to establish that the oscillations are driven by on/off switching of phosphofructokinase. In the case of intact yeast cells, we find that the instability leading to the appearance of oscillations is caused by the stoichiometry of the ATP-ADP-AMP system and the allosteric regulation of phosphofructokinase, whereas frequency control is distributed over the reaction network. Notably, the NAD+/NADH ratio modulates the frequency of the oscillations without affecting the instability. This is important for understanding the mutual synchronization of oscillations in the individual yeast cells, as synchronization is believed to occur via acetaldehyde, which in turn affects the frequency of oscillations by changing this ratio.


Asunto(s)
Glucólisis , Fosfofructoquinasas/fisiología , Saccharomyces cerevisiae/fisiología , Adenosina Trifosfato/metabolismo , Cinética , Modelos Biológicos , NAD/metabolismo
14.
Biophys Chem ; 200-201: 18-26, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25863195

RESUMEN

Synchronous metabolic oscillations can be induced in yeast by addition of glucose and removal of extracellular acetaldehyde (ACAx). Compared to other means of ACAx removal, cyanide robustly induces oscillations, indicating additional cyanide reactions besides ACA to lactonitrile conversion. Here, (13)C NMR is used to confirm our previous hypothesis, that cyanide directly affects glycolytic fluxes through reaction with carbonyl-containing compounds. Intracellularly, at least 3 cyanohydrins were identified. Extracellularly, all signals could be identified and lactonitrile was found to account for ~66% of total cyanide removal. Simulations of our updated computational model show that intracellular cyanide reactions increase the amplitude of oscillations and that cyanide addition lowers [ACA] instantaneously. We conclude that cyanide provides the following means of inducing global oscillations: a) by reducing [ACAx] relative to oscillation amplitude, b) by targeting multiple intracellular carbonyl compounds during fermentation, and c) by acting as a phase resetting stimulus.


Asunto(s)
Glucosa/metabolismo , Nitrilos/metabolismo , Saccharomyces cerevisiae/metabolismo , Acetaldehído/química , Fermentación , Glucosa/química , Glucólisis , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Nitrilos/química
15.
Phys Rev E Stat Nonlin Soft Matter Phys ; 68(2 Pt 1): 020902, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-14524946

RESUMEN

In a tissue of oscillatory cells the active intracellular medium is surrounded by a membrane and the cells are separated by inactive extracellular medium. The synchronization properties of a system of such coupled oscillatory cells have been emulated using the light-sensitive Belousov-Zhabotinsky reaction. Experimental results for four coupled cells are confirmed by numerical simulations. We have furthermore demonstrated the existence of antispirals and antipacemaker waves with inward propagating waves in larger cell assemblies of this type. Such dynamical structures are extremely rare in homogeneous chemical systems where the generic behavior is normal spirals and target patterns with outward-moving waves.


Asunto(s)
Células Cultivadas , Oscilometría , Animales , Fenómenos Biofísicos , Biofisica , Difusión , Modelos Teóricos , Factores de Tiempo
16.
Dan Med J ; 61(3): A4796, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24814915

RESUMEN

INTRODUCTION: Approximately 5,000 Danish patients are being treated for end-stage renal disease, for which the two treatment options are dialysis and transplantation. The objective of this study was to estimate the cost-effectiveness of kidney transplantation versus dialysis from a public health-care perspective. MATERIAL AND METHODS: A cost-utility analysis was conducted using a decision analytic model. The model was designed as a Markov model in which all relevant costs and effects of the two alternative treatments were included. Deterministic data were used alongside the best available evidence from the literature. To estimate the overall uncertainty concerning the incremental cost-effectiveness ratio (ICER), a probabilistic sensitivity analysis with second-order Monte Carlo simulations was carried out on a hypothetical cohort of 10,000 patients. RESULTS: The cost per quality-adjusted life year (QALY) was 1,032,934 DKK for dialysis compared with 810,516 DKK for transplantation. When comparing kidney transplantation with dialysis, kidney transplantation was cost-saving and resulted in additional QALYs. When taking the overall uncertainty associated with the ICER into account, an incremental cost-effectiveness scatter plot supported that transplantation was dominating and that the results were robust. In addition, a cost-effectiveness acceptability curve showed that transplantation had a 99.93% likelihood of being cost-effective at a willingness-to-pay value of 0 DKK. CONCLUSION: The cost-effectiveness ratio was favourable for kidney transplantation when compared with dialysis. In view of this, it was concluded that transplantation is preferable to dialysis when treating patients with end-stage renal disease. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.


Asunto(s)
Trasplante de Riñón/economía , Diálisis Renal/economía , Análisis Costo-Beneficio , Árboles de Decisión , Dinamarca , Humanos , Cadenas de Markov , Método de Montecarlo , Años de Vida Ajustados por Calidad de Vida
17.
Dan Med J ; 61(8): A4886, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25162445

RESUMEN

INTRODUCTION: Children with central nervous system (CNS) tumours often have a long symptom interval before diagnosis. We investigated delays in diagnosis and surgical management after the first admission with tumour-related symptoms. MATERIAL AND METHODS: This study reviewed the medical records of 46 consecutive children with a CNS tumour admitted to a paediatric department. Clinical findings at the time of the first admission, duration of symptoms, time to radiological diagnosis and time to initial surgical procedures were recorded. RESULTS: The series comprised 26 supratentorial, 19 fossa posterior and one spinal tumour with equal numbers of high-grade and low-grade tumours. Headache, vomiting and lethargy were the most frequent symptoms, and pre-admission delay depended on tumour grade as well as location. Six cases had been diagnosed prior to admission; of the 40 undiagnosed cases, 32 (80%) were scanned within four days, but in four cases (10%) diagnosis was delayed for more than a week. Resection was performed within four days of diagnosis in 68% of children with resectable tumours (21/31). Initial surgical management of tumours causing hydrocephalus was completed within four days of diagnosis in 83% (20/24). CONCLUSION: Delay in diagnosis and surgical management after the primary admission with symptoms caused by a tumour may influence the outcome negatively. In this review from a small centre, the majority of the cases were diagnosed and managed surgically within four days of admission and diagnosis, respectively. Criteria for good performance, i.e. accepted standards for time to diagnosis and intervention, need to be specified. FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Eficiencia Organizacional , Servicio de Oncología en Hospital , Neoplasias de la Médula Espinal/diagnóstico , Adolescente , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Niño , Preescolar , Diagnóstico Tardío , Detección Precoz del Cáncer , Femenino , Cefalea/etiología , Hospitalización , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Lactante , Letargia/etiología , Masculino , Estudios Retrospectivos , Neoplasias de la Médula Espinal/complicaciones , Neoplasias de la Médula Espinal/cirugía , Factores de Tiempo , Trastornos de la Visión/etiología , Vómitos/etiología
18.
Brain Pathol ; 24(4): 360-70, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24521322

RESUMEN

Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto-1 (CR-1) has a key regulatory role in embryogenesis, while in adult tissue re-expression of CR-1 has been correlated to malignant progression in solid cancers of non-neuronal origin. As CR-1 expression has yet to be described in cerebral cancer and CR-1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR-1 in the context of expression in GBM. The study was performed using enzyme-linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low-grade glioma patients. Within the patient cohort, we found high CR-1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR-1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR-1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Proteínas Ligadas a GPI/metabolismo , Glioblastoma/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores/metabolismo , Western Blotting , Línea Celular Tumoral , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Masculino , Ratones , Persona de Mediana Edad , Trasplante de Neoplasias , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
19.
FEBS J ; 279(23): 4410-20, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23072639

RESUMEN

Coherent glycolytic oscillations in Saccharomyces cerevisiae are a multicellular property induced by addition of glucose to a starved cell population of sufficient density. However, initiation of oscillations requires an additional perturbation, usually addition of cyanide. The fate of cyanide during glycolytic oscillations has not previously been studied, and is the subject of the present paper. Using a cyanide electrode, a substantial decrease in cyanide concentration was observed. In the pH range 6-7, we found experimentally that the electrode behaves reasonably well, provided changes in pH are taken into account. To our knowledge, use of a cyanide electrode to study cyanide dynamics in living biological systems is new. Cyanide was found to enter starving yeast cells in only negligible amounts, and did not react significantly with glucose. Thus, cyanide consumption must be explained by reactions with glycolytic intermediates and evaporation. Evaporation and reaction with the signalling substance, extracellular acetaldehyde (ACA(x)) only explains the observed cyanide removal if [ACA(x)] is improbably high. Furthermore, differences in NADH traces upon cyanide addition before or after glucose addition strongly suggest that cyanide also reacts with intracellular carbonyl-containing metabolites. We show that cyanide reacts with pyruvate (Pyr) and dihydroxyacetone phosphate in addition to ACA, and estimate their rate constants. Our results strongly suggest that the major routes of cyanide removal during glycolysis are reactions with pyruvate and ACA. Cyanide removal by all carbonyl-containing intermediates led to a lower mean [ACA(x) ], thereby increasing the amplitude of [ACA(x) ] oscillations.


Asunto(s)
Cianuros/farmacología , Saccharomyces cerevisiae/metabolismo , Acetaldehído/metabolismo , Dihidroxiacetona Fosfato/metabolismo , Glucosa/metabolismo , Concentración de Iones de Hidrógeno
20.
Ugeskr Laeger ; 173(36): 2203-4, 2011 Sep 05.
Artículo en Danés | MEDLINE | ID: mdl-21893007

RESUMEN

We present a case of neurocysticercosis in a 12-year old refugee from Zambia. Magnetic resonance imaging demonstrated a solitary, ring enhancing cystic lesion located subcortically in the left parietal lobe. Despite extensive diagnostic workup it was not possible to rule out alternative differential diagnoses. Serological tests for neurocysticercosis came out negative. The lesion was removed en bloc using microsurgical technique. Subsequent histological examination revealed a thick-walled cyst containing a cysticercus identifiable as a Taenia solium.


Asunto(s)
Neurocisticercosis/cirugía , Encéfalo/patología , Niño , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Zambia
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