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At least 523 records · Page 29Linked to original sources
PubMed2000

Alveolar environment influences the metabolic and biophysical properties of exogenous surfactants.

Several factors have been shown to influence the efficacy of exogenous surfactant therapy in the acute respiratory distress syndrome. We investigated the effects of four different alveolar environments (control, saline-lavaged, N-nitroso-N-methylurethane, and hydrochloric acid) on the metabolic and functional properties of two exogenous surfactant preparations: bovine lipid extract surfactant and recombinant surfactant-associated protein (SP) C drug product (rSPC) administered to each of these groups. The main difference between these preparations was the lack of SP-B in the rSPC. Our results demonstrated differences in the large aggregate pool sizes recovered from each of the experimental groups. We also observed differences in SP-A content, surface area cycling characteristics, and biophysical activities of these large aggregate forms after the administration of the two exogenous surfactant preparations. We conclude that the alveolar environment plays a critical role, influencing the overall efficacy of exogenous surfactant therapy. Thus further preclinical studies are warranted to investigate the specific factors within the alveolar environment that lead to the differences observed in this study.

Animals↗
PubMed2002

Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity.

Sphingolipids represent a diverse group of bioactive lipid species that are generated intracellularly in response to tumor necrosis factor-alpha (TNF-alpha) and are implicated as potential mediators of acute lung injury. The purpose of these studies was to determine whether there was an extracellular, TNF-alpha-regulated pool of sphingolipids in the alveolus that modulates the surface tension lowering capacity of pulmonary surfactant. Intratracheal instillation of TNF-alpha in adult rats led to a twofold increase in the amount of surfactant-associated ceramide and tended to decrease levels of sphingomyelin without significantly altering sphingosine or sphinganine content. TNF-alpha induction of alveolar ceramide was associated with nearly an 80% increase in acid sphingomyelinase activity recovered in cell-free alveolar lavage. Ceramide administered in a dose-dependent manner potently antagonized the surface tension lowering effects of natural surfactant in vitro. Intratracheal TNF-alpha and ceramide treatment of rats significantly increased lung permeability, as was evidenced by extravasation of Evans blue dye into alveolar lavage and lung tissue. Thus these studies are the first to demonstrate the existence of a cytokine-regulated alveolar pool of sphingomyelin hydrolysis products that impairs the biophysical properties of the alveolar surfactant film. The results also suggest the presence of a secretory alveolar sphingomylinase that is TNF-alpha responsive and mediates effects of the cytokine on alveolar sphingolipid metabolism.

Animals↗
PubMed2002

Mechanical ventilation of isolated rat lungs changes the structure and biophysical properties of surfactant.

Mechanical ventilation is an essential but potentially harmful therapeutic intervention for patients with acute lung injury. The objective of this study was to investigate the effects of mechanical ventilation on large-aggregate surfactant (LA) structure and function. Isolated rat lungs were randomized to either a nonventilated control group, a relatively noninjuriously ventilated group [1 h, 10 ml/kg tidal volume, 3 cmH(2)O positive end-expiratory pressure (PEEP)], or an injuriously ventilated group (1 h, 20 ml/kg tidal volume, 0 cmH(2)O PEEP). Injurious ventilation resulted in significantly decreased lung compliance compared with the other two groups. LA structure, as determined by electron microscopy, revealed that LA from the injurious group had significantly lower amounts of organized lipid-protein structures compared with LA obtained from the other groups. Analysis of the biophysical properties by using a captive bubble surfactometer demonstrated that adsorption and surface tension reduction were significantly impaired with LA from the injuriously ventilated lungs. We conclude that the injurious mechanical ventilation impairs LA function and that this impairment is associated with significant morphological alterations.

Adsorption↗
PubMed2003

Biophysical basis for inner ear decompression sickness.

Isolated inner ear decompression sickness (DCS) is recognized in deep diving involving breathing of helium-oxygen mixtures, particularly when breathing gas is switched to a nitrogen-rich mixture during decompression. The biophysical basis for this selective vulnerability of the inner ear to DCS has not been established. A compartmental model of inert gas kinetics in the human inner ear was constructed from anatomical and physiological parameters described in the literature and used to simulate inert gas tensions in the inner ear during deep dives and breathing-gas substitutions that have been reported to cause inner ear DCS. The model predicts considerable supersaturation, and therefore possible bubble formation, during the initial phase of a conventional decompression. Counterdiffusion of helium and nitrogen from the perilymph may produce supersaturation in the membranous labyrinth and endolymph after switching to a nitrogen-rich breathing mixture even without decompression. Conventional decompression algorithms may result in inadequate decompression for the inner ear for deep dives. Breathing-gas switches should be scheduled deep or shallow to avoid the period of maximum supersaturation resulting from decompression.

Adult↗
PubMed2002

A biophysical model of nonlinear dynamics underlying plateau potentials and calcium spikes in purkinje cell dendrites.

Computational capabilities of Purkinje cells (PCs) are central to the cerebellum function. Information originating from the whole nervous system converges on their dendrites, and their axon is the sole output of the cerebellar cortex. PC dendrites respond to weak synaptic activation with long-lasting, low-amplitude plateau potentials, but stronger synaptic activation can generate fast, large amplitude calcium spikes. Pharmacological data have suggested the involvement of only the P-type of Ca channels in both of these electric responses. However, the mechanism allowing this Ca current to underlie responses with such different dynamics is still unclear. This mechanism was explored by constraining a biophysical model with electrophysiological, Ca-imaging, and single ion channel data. A model is presented here incorporating a simplified description of [Ca](i) regulation and three ionic currents: 1) the P-type Ca current, 2) a delayed-rectifier K current, and 3) a generic class of K channels activating sharply in the sub-threshold voltage range. This model sustains fast spikes and long-lasting plateaus terminating spontaneously with recovery of the resting potential. Small depolarizing, tonic inputs turn plateaus into a stable membrane state and endow the dendrite with bistability properties. With larger tonic inputs, the plateau remains the unique equilibrium state, showing long traces of transient inhibitory inputs that are called "valley potentials" because their dynamics mirrors that of inverted, finite-duration plateaus. Analyzing the slow subsystem obtained by assuming instantaneous activation of the delayed-rectifier reveals that the time course of plateaus and valleys is controlled by the slow [Ca](i) dynamics, which arises from the high Ca-buffering capacity of PCs. A bifurcation analysis shows that tonic currents modulate sub-threshold dynamics by displacing the resting state along a hysteresis region edged by two saddle-node bifurcations; these bifurcations mark transitions from finite-duration plateaus to bistability and from bistability to valley potentials, respectively. This low-dimensionality model may be introduced into large-scale models to explore the role of PC dendrite computations in the functional capabilities of the cerebellum.

Algorithms↗
PubMed1998

Biophysical characterization and functional consequences of a slowly inactivating potassium current in neostriatal neurons.

Neostriatal spiny projection neurons can display a pronounced delay in their transition to action potential discharge that is mediated by a slowly developing ramp depolarization. The possible contribution of a slowly inactivating A-type K+ current (IAs) to this delayed excitation was investigated by studying the biophysical and functional properties of IAs using whole cell voltage- and current-clamp recording from acutely isolated neostriatal neurons. Isolation of IAs from other voltage-gated, calcium-independent K+ currents was achieved through selective blockade of IAs with low concentrations (10 microM) of the benzazepine derivative, 6-chloro-7,8-dihydroxy-3-allyl- 1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepine (APB; SKF82958) and subsequent current subtraction. Examination of the voltage dependence of activation showed that IAs began to flow at approximately -60 mV in response to depolarization. The voltage dependence of inactivation revealed that approximately 50% of IAs channels were available at the normal resting potential (-80 mV) of these cells, but that only 20% of the channels were available at membrane potentials corresponding to spike threshold (about -40 mV). At these depolarized membrane potentials, the rate of activation was moderately rapid (tau approximately 60 ms), whereas the rate of inactivation was slow (tau approximately 1.5 s). The time course of removal of inactivation of IAs at -80 mV also was relatively slow (tau approximately 1.0 s). The subthreshold availability of IAs combined with its rapid activation and slow inactivation rates suggested that this current should be capable of dampening the onset of prolonged depolarizing responses, but over time its efficacy should diminish, slowly permitting the membrane to depolarize toward spike threshold. Voltage recording experiments confirmed this hypothesis by demonstrating that application of APB at a concentration (10 microM) that selectively blocks IAs substantially decreased the latency to discharge and increased the frequency of firing of neostriatal neurons. The properties of IAs suggest that it should play a critical role in placing the voltage limits on the recurring episodes of subthreshold depolarization which are characteristic of spiny neurons recorded in vivo. However, the voltage dependence and recovery kinetics of inactivation of IAs predict that its effectiveness will vary exponentially with the level and duration of hyperpolarization which precedes depolarizing episodes. Thus long periods of hyperpolarization should increase the availability of IAs and dampen succeeding depolarizations; whereas brief epochs of hyperpolarization should not sufficiently remove inactivation of IAs, thereby reducing its ability to limit subsequent depolarizing responses.

Action Potentials↗
PubMedDate not supplied

Role of biophysical specialization in cholinergic modulation in neurons of the ventral cochlear nuclei.

In contacting arrays of different types of neurons whose axons have differing targets in the brain stem, the auditory pathway is subdivided into parallel ascending pathways, each of which carries a different type of information. Several distinct arrays of neurons in the ventral cochlear nuclei have anatomical and biophysical specializations which enable them to extract differing facets of acoustic information and to convey it up the auditory pathway. T stellate cells have higher input resistances and have lower firing thresholds than bushy or octopus cells, enabling their firing to be modulated by small currents. Cholinergic currents, driven by neurons in the ventral nucleus of the trapezoid body that are likely to include medial olivocochlear efferents, excite T stellate cells, but have subtle effects on the firing of bushy cells, and have no detectable influence on octopus cells and D stellate cells. We suggest that cholinergic excitation of T stellate cells contributes toward shifting their acoustic dynamic ranges and increasing the encoding of spectral peaks in noisy conditions and in awake animals.

Acetylcholine↗
PubMedDate not supplied

Fetal biophysical profile and cerebro-umbilical ratio in assessment of perinatal outcome in growth-restricted fetuses.

AIM: To examine the value of the fetal biophysical profile (FBP) and the Doppler cerebro-umbilical ratio (C/U) in the assessment of perinatal outcome in growth-restricted and hypoxic fetuses. STUDY DESIGN: The prospective clinical study included 87 pregnant women with singleton pregnancies at 28-42 weeks of gestation with clinically verified intrauterine growth restriction (IUGR). After assessment of FBP, flow velocity waveforms from the umbilical and middle cerebral arteries were recorded and the C/U ratio was calculated. The C/U ratio and FBP were assessed twice a week. At delivery, umbilical arterial pH, the occurrence of meconium-stained amniotic fluid (MAF), Apgar score at 5 min and the incidence of cesarean sections were used as outcome parameters. RESULTS: The mean FBP value was 5.5 +/- 0.96 in cases with MAF, and 6.88 +/- 0.26 in cases without MAF. Also, there was no statistical significance in the relation between the C/U ratio and the appearance of MAF. At pH >7.2, the mean FBP value was 7.11 +/- 0.23, while it was 2.83 +/- 0.79 in newborns with acidosis. Both FBP and C/U values were statistically correlated with pH (p < 0.01). The mean umbilical arterial pH was 7.31 +/- 0.0 at a C/U ratio of >/=1 and 7.21 +/- 0.03 at a C/U ratio of <1. In cases with Apgar scores of 8-10, the mean FBP value was 7.28 +/- 0.23, at Apgar scores of 5-7 it was 3.9 +/- 0.52, while at Apgar scores of 0-4 the mean FBP value was 1.5 +/- 0.5. The mean Apgar score at 5 min was 9.54 +/- 0.09 at a C/U ratio of >/=1, and 8.12 +/- 0.49 at a C/U ratio of <1. The mean FBP value in cases of vaginal delivery was 7.55 +/- 0.31. In cesarean section deliveries, the mean FBP value was 5.97 +/- 0.37. Also, there was a high frequency of cesarean sections in growth-restricted fetuses with a C/U ratio of <1 (p < 0.05), i.e. slightly less than FBP. CONCLUSIONS: FBP and C/U ratio were associated with low arterial pH, low Apgar score and the rate of cesarean sections (p < 0.05), but there was no association between FBP or C/U ratio and the appearance of MAF (p > 0.5). Due to their good predictive value the FBP and C/U ratio could be used in the prenatal monitoring of growth-retarded and hypoxic fetuses. These two methods can be used as important parameters in the decision to end pregnancies with IUGR, when pathological values occur. Thus a reduction in perinatal morbidity, mortality and the incidence of infants with poor neurologic outcome can be expected.

Biophysical Phenomena↗
PubMed2004

How the shape of pre- and postsynaptic signals can influence STDP: a biophysical model.

Spike-timing-dependent plasticity (STDP) is described by long-term potentiation (LTP), when a presynaptic event precedes a postsynaptic event, and by long-term depression (LTD), when the temporal order is reversed. In this article, we present a biophysical model of STDP based on a differential Hebbian learning rule (ISO learning). This rule correlates presynaptically the NMDA channel conductance with the derivative of the membrane potential at the synapse as the postsynaptic signal. The model is able to reproduce the generic STDP weight change characteristic. We find that (1) The actual shape of the weight change curve strongly depends on the NMDA channel characteristics and on the shape of the membrane potential at the synapse. (2) The typical antisymmetrical STDP curve (LTD and LTP) can become similar to a standard Hebbian characteristic (LTP only) without having to change the learning rule. This occurs if the membrane depolarization has a shallow onset and is long lasting. (3) It is known that the membrane potential varies along the dendrite as a result of the active or passive backpropagation of somatic spikes or because of local dendritic processes. As a consequence, our model predicts that learning properties will be different at different locations on the dendritic tree. In conclusion, such site-specific synaptic plasticity would provide a neuron with powerful learning capabilities.

Action Potentials↗
PubMed1993

Biophysical approaches to salivary mucin structure, conformation and dynamics.

Our understanding of the origins of the physical and biochemical properties of mucous glycoproteins is incomplete and not with out controversy. Recent molecular biological and biophysical studies revealing the architecture and solution structure and dynamics of a series of salivary mucins, invaluable toward resolving many of these questions, are discussed. Mucins are very large, structurally heterogeneous, and highly expanded molecules with the carbohydrate playing a key role in maintaining the extended mucin conformation.

Amino Acid Sequence↗
PubMed1981

Biophysical and morphological correlates of kinetic change and death in a starved human melanoma cell line.

An investigation was made of the sequential biophysical and morphological changes that occur as cultured human melanoma cells (MM96) outgrow their supply of nutrient. Simultaneous buoyant-density and velocity-sedimentation fractionation experiments were used to characterize cells from 3 kinetically differing types of culture. Cells from exponential cultures were large, moderately dense and rapidly sedimenting; cells from post-exponential cultures were of intermediate size, less dense and much more slowly sedimenting; and dye-excluding cells from reproductively non-viable late post-exponential cultures were small, of widely variable though generally high density and sedimented moderately rapidly. Although reproductive viability was high in cells from both exponential and post-exponential cultures, depletion of clonogenic cells was seen at the extremes of the distribution profiles of cells fractionated by either method. This was particularly evident at the low-density extreme of the buoyant-density profiles where cells retained viability despite their loss of proliferative potential. As cells became post-exponential, nuclear size diminished in parallel with cell size, the number of microvilli declined, mitochondria condensed, cytoplasm vacuolated, the frequency of osmiophilic vacuolar inclusions rose, chromatin clumped and nucleoli became prominent. Progression to a reproductively non-viable late post-exponential state resulted in a continued parallel fall in nuclear size, increased cytoplasmic blebbing, further mitochondrial condensation, an increased proportion of cytoplasmic vacuoles containing osmiophilic material, the major part of which was melanin, and further clumping and margination of chromatin. Cells progressed rapidly from this newly described pre-apoptotic state to death by apoptosis, a process characterized by the budding and division of cells into a number of ultrastructurally well-preserved membrane-bound fragments.

Biophysical Phenomena↗
PubMed1982

Biophysics of underwater hearing in anuran amphibians.

A standing wave tube apparatus was used to determine the biophysical basis of underwater hearing sensitivity in 3 species of Rana and in Xenopus laevis. A speaker inside the base of a vertical, water-filled 3 m steel pipe produced standing waves. Pressure and particle motion were measured with a hydrophone and geophone respectively and were spatially 90 degrees out of phase along the length of the tube. Microphonic responses were recorded from the inner ear of frogs lowered through pressure and particle motion maxima and minima. The air-filled lungs of whole frogs produced distortions of the sound field. Preparations of heads with only an air-filled middle ear produced little distortion and showed clear pressure tracking at sound intensities 10-20 dB above hearing thresholds from 200-3000 Hz. Filling the middle ear with water decreased or abolished microphonic responses. Severing the stapes reduced responses except at certain frequencies below about 1000 Hz which varied with body size and likely represent resonant frequencies of the middle ear cavity. We conclude that the frog species examined respond to underwater sound pressure from about 200-3000 Hz with the middle ear cavity responsible for pressure transduction.

Animals↗
PubMed2001

Continuous UVB irradiation to modify the biophysical properties and protein conformation of rat skin.

In order to determine the continuous irradiation effects of UVB on the skin of live Sprague Dawley (SD) rats, the changes in biophysical properties and protein conformation of the skin were studied. The continuous UVB irradiation affecting the water content, skin color and protein structure of the rat skin was investigated by using a skin surface hygrometer, a Chroma meter and an attenuated total reflection (ATR)/Fourier transform infrared (FT-IR) spectroscopy. Test areas on the dorsal skin were continuously irradiated with 600 +/- 10 microW/cm2 UVB for 56 h. Part of the dorsal skin was covered with a bandage as a non-irradiated control. The results indicated that the water content of the irradiated skin decreased with UVB irradiation, but the non-irradiated control skin exhibited a higher level of water content. The decrease in the skin's water-binding capacity from cracks induced by continuous UVB irradiation, and the occlusive dressing of the non-irradiated skin to prevent water loss and form full hydration might be responsible for the results. The decrease of L* value and the increase in a*, b* and delta E values in the skin color parameters with UVB irradiation indicates an incremental darkening of the skin and a marked increase in erythema. However, there was no significant change in skin color for the non-irradiated control skin. A slight modification of the protein secondary structure in the skin after continuous UVB irradiation was also evidenced by transforming the alpha-helix structure into a beta-sheet structure after long-term continuous UVB irradiation. Continuous UVB irradiation of SD rat skin may decrease the skin's water-binding capacity, cause darkening, increase erythema and modify the protein secondary structure of the skin.

Animals↗
PubMed2006

Biophysical studies on the differentiation of human CD14+ monocytes into dendritic cells.

Dendritic cells (DCs), which are the most efficient antigen-presenting cells (APCs) currently known, can be derived from CD14+ monocytes (DC predecessor cells) in vitro. Immature DCs actively take up antigens and pathogens, generate major histocompatability complex-peptide complexes, and migrate from the sites of antigen acquisition to secondary lymphoid organs to become mature dendritic cells that interact with and stimulate T-lymphocytes. During this process, the cells must undergo deformation to translocate through several barriers, including the basement membrane and interstitial connective tissue in the blood vessel wall. To further understand the mechanisms of the activation of immunological responses and the migration from peripheral tissue to secondary lymphoid organs, we have applied biophysical and microrheological methods to study the development processes of DCs in vitro. The results showed that membrane fluidity, osmotic fragility, membrane viscoelastic properties, infrared spectroscopy, and cytoskeleton organization of DCs exhibit significant differences in different developmental stages.

Biophysical Phenomena↗
PubMed2006

Biophysical model of AMPA receptor trafficking and its regulation during long-term potentiation/long-term depression.

AMPA receptors mediate the majority of fast excitatory synaptic transmission in the CNS, and evidence suggests that AMPA receptor trafficking regulates synaptic strength, a phenomenon implicated in learning and memory. There are two major mechanisms of AMPA receptor trafficking: exocytic/endocytic exchange of surface receptors with intracellular receptor pools, and the lateral diffusion or hopping of surface receptors between the postsynaptic density and the surrounding extrasynaptic membrane. In this paper, we present a biophysical model of these trafficking mechanisms under basal conditions and during the expression of long-term potentiation (LTP) and depression (LTD). We show how our model reproduces a wide range of physiological data, and use this to make predictions regarding possible targets of second-messenger pathways activated during the induction phase of LTP/LTD.

Animals↗
PubMed1999

Liposomes: from biophysics to the design of peptide vaccines.

Liposomes (lipid-based vesicles) have been widely studied as drug delivery systems due to their relative safety, their structural versatility concerning size, composition and bilayer fluidity, and their ability to incorporate almost any molecule regardless of its structure. Liposomes are successful in inducing potent in vivo immunity to incorporated antigens and are now being employed in numerous immunization procedures. This is a brief overview of the structural, biophysical and pharmacological properties of liposomes and of the current strategies in the design of liposomes as vaccine delivery systems.

Adjuvants, Immunologic↗
PubMed2004

Biophysic evaluation of bone quality-application of Fourier transform infrared spectroscopy and phosphorus-31 solid-state nuclear magnetic resonance spectroscopy.

In this review, we focus on findings obtained with biophysic techniques, Fourier transformed infrared (FTIR) spectroscopy and phosphorus-31 solid-state nuclear magnetic resonance (31P solid-state NMR) spectroscopy, which may allow us to evaluate bone quality and to predict bone strength. FTIR measures the absorption energy that produces an increase in the vibrational or rotational energy of atoms or groups of atoms within the molecule. FTIR spectroscopy allows us to examine the relative amount of minerals and matrix content and the arrangement of apatite and organic matrix. FTIR spectroscopy should become an important tool, because the relative amount of minerals and the arrangement of apatite and organic matrix could be a measure for evaluating bone quality. 31P solid-state NMR spectroscopy is useful for evaluating the quality of bone and predicting bone strength by calculating the spine-lattice relaxation time (T1) of bone. 31P solid-state NMR imaging can be used to measure quantitatively the mass of hydroxyapatite. The T1 relaxation time of both bone and deficient hydroxyapatite was much longer than that of pure hydroxyapatite. T1 relaxation time is one of the promising indices of bone quality.

Animals↗
PubMed1994

Clothing and exercise. I: Biophysics of heat transfer between the individual, clothing and environment.

Despite large environmental variations, the human body maintains a tightly regulated core temperature. Effective thermoregulation must balance the interaction between skin surface, clothing and ambient air. Indices of thermal stress (wet bulb globe temperature, heat stress index, maximum evaporation rate, required evaporative rate and wind chill) provide valuable information concerning the heat exchange between the individual and the environment, and serve as protective guidelines while working in environmental extremes. The role of clothing, as an interactive barrier, greatly affects thermal balance. Clothing is varied according to prevailing environmental conditions, metabolic heat production, gender and age differences, fabric thermal properties, garment design and intended use. Models (static, dynamic and human) have investigated the biophysical transfer of heat between the skin surface area, clothing and ambient air. Additionally, the role of metabolic heat production during exercise can greatly influence tolerance to thermal stress during a variety of environmental conditions.

Adolescent↗