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PubMed2001

Evidence from the Pacific troposphere for large global sources of oxygenated organic compounds.

The presence of oxygenated organic compounds in the troposphere strongly influences key atmospheric processes. Such oxygenated species are, for example, carriers of reactive nitrogen and are easily photolysed, producing free radicals-and so influence the oxidizing capacity and the ozone-forming potential of the atmosphere-and may also contribute significantly to the organic component of aerosols. But knowledge of the distribution and sources of oxygenated organic compounds, especially in the Southern Hemisphere, is limited. Here we characterize the tropospheric composition of oxygenated organic species, using data from a recent airborne survey conducted over the tropical Pacific Ocean (30 degrees N to 30 degrees S). Measurements of a dozen oxygenated chemicals (carbonyls, alcohols, organic nitrates, organic pernitrates and peroxides), along with several C2-C8 hydrocarbons, reveal that abundances of oxygenated species are extremely high, and collectively, oxygenated species are nearly five times more abundant than non-methane hydrocarbons in the Southern Hemisphere. Current atmospheric models are unable to correctly simulate these findings, suggesting that large, diffuse, and hitherto-unknown sources of oxygenated organic compounds must therefore exist. Although the origin of these sources is still unclear, we suggest that oxygenated species could be formed via the oxidation of hydrocarbons in the atmosphere, the photochemical degradation of organic matter in the oceans, and direct emissions from terrestrial vegetation.

Journal Article↗
PubMed2006

Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI.

Effective pulmonary gas exchange relies on the free diffusion of gases across the thin tissue barrier separating airspace from the capillary red blood cells (RBCs). Pulmonary pathologies, such as inflammation, fibrosis, and edema, which cause an increased blood-gas barrier thickness, impair the efficiency of this exchange. However, definitive assessment of such gas-exchange abnormalities is challenging, because no methods currently exist to directly image the gas transfer process. Here we exploit the solubility and chemical shift of (129)Xe, the magnetic resonance signal of which has been enhanced by 10(5) with hyperpolarization, to differentially image its transfer from the airspaces into the tissue barrier spaces and RBCs in the gas exchange regions of the lung. Based on a simple diffusion model, we estimate that this MR imaging method for measuring (129)Xe alveolar-capillary transfer is sensitive to changes in blood-gas barrier thickness of approximately 5 microm. We validate the successful separation of tissue barrier and RBC images and show the utility of this method in a rat model of pulmonary fibrosis where (129)Xe replenishment of the RBCs is severely impaired in regions of lung injury.

Animals↗
PubMed1994

A modified fluid percussion device.

This report examines a modified fluid percussion device with specific improvements made to address deficiencies found in previously reported devices. These improvements include the use of a cylindrical saline reservoir made of stainless steel, placement of the reservoir in a 15-degree head-up position for the easy release of air bubbles, placement of the fluid flushing outlet and the pressure transducer close to the piston on the same plane, with both perpendicular to the direction of the piston, and adjustable reservoir volume to vary the waveform of the pressure pulse, and a metallic central injury screw secured to the animal's skull over the exposed dura. Using this device, midline fluid percussion (MFP) and lateral fluid percussion (LFP) injuries were performed in 70 rats. Histopathologic findings included diffuse axonal injury in the MFP model and cortical contusion in the LFP model. Survival rate was 41.4% in MFP animals and 100% in LFM animals when the device settings were 178 mm3 of the cylindrical reservoir and 50 degrees-60 degrees in height of the pendulum. Our results suggest that this modified fluid percussion device may offer significant improvements over previously reported fluid percussion models for use in experimental head injury.

Animals↗
PubMed2000

Rates of protein transport across rat alveolar epithelial cell monolayers.

The transport of model proteins, ranging from 12,300 to 150,000 Da, across tight rat alveolar epithelial cell monolayers (> 2000omegacm2) grown on polycarbonate filters, was studied. Model proteins were 14C-cytochrome c, 14C-ovalbumin, granulocyte-colony stimulating factor (G-CSF), 14C-bovine serum albumin (BSA), 125I-transferrin, and 14C-immunoglobulin G. Cytochrome c was extensively metabolized, as indicated by < 10% of the dose being translocated in intact form. This contrasts with 20-80% for the other model proteins studied. The flux of cytochrome c and G-CSF was symmetric in the apical-to-basolateral (ab) and basolateral-to-apical (ba) directions. By contrast, the flux of intact ovalbumin, BSA, transferrin and immunoglobulin G showed asymmetry, with the ab flux being higher by 2-5 times. There was no relationship between ab or ba fluxes and the molecular weights of these four model proteins. Since some of the proteins were translocated at much greater rates than are consistent with restricted diffusion or pinocytosis, receptor-mediated or adsorptive transcytosis may be involved.

Animals↗
PubMed1989

Effects of environmental O2 on blood flow and diffusing capacity in amphibian skin.

The effects of local environmental PO2 on cutaneous blood flow (Q) and the membrane diffusing capacity of the skin (D) were investigated in the leopard frog, Rana pipiens, and the lungless salamander, Desmognathus quadramaculatus. Halothane anesthetized animals were equilibrated with Freon-22 (Fr) and acetylene (Ac) in a box. A gas mixture containing either 0, 20 or 40% O2, respectively, in N2 and initially free of Fr and Ac was drawn through a small sample chamber on the abdomen. The excretion of Fr and Ac into the chamber was analyzed with a mass spectrometer. These conditions allowed the determination of the cutaneous conductance to Fr (GFr) and Ac (GAc) at the 3 levels of local environmental O2. GFr and GAc of the isolated skin and the blood solubilities of the 2 gases were also determined. To estimate Q, DAc and DFr, the data were analyzed with a homogeneous single capillary model. In the frog, Q varied directly with sample chamber [O2], but chamber [O2] had no effect on D. In the salamander, O2 had no effect on either Q or D. The results indicate that regulation of cutaneous gas exchange in the frog by local environmental O2 only involves alterations in Q. Similar control of cutaneous gas exchange is absent in the lungless salamander.

Acetylene↗
PubMed2026

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans↗
PubMed1994

Skeletal muscle oedema and muscle fibre necrosis during septic shock. Observations with a porcine septic shock model.

In domestic pigs, intermitted application of Escherichia coli-endotoxin was used to create an animal model for a prolonged hypo- and hyperdynamic septic shock-like state and to investigate mechanisms of multiple organ failure. Here, we describe the changes in skeletal muscle after 18 h (2 animals) and 48 h (6 animals) of septic shock. Two pigs for each observation period that received physiologic saline solutions instead of endotoxin served as controls. The earliest lesions were endothelial cell damage with endomysial oedema and swelling of mitochondria in muscle fibres. With increasing degree of endothelial cell damage, pericytes showed degenerative changes with cytoplasmic fragmentation and karyolysis. After 48 h of shock, endomysial oedema was increased with fibrinogen present. Muscle fibre diameters were increased and swollen mitochondria and segmental necrosis of muscle fibres were frequently observed. However, phagocytic reaction or regenerative changes were not detected. In this respect, skeletal muscle lesions in septic shock differ from ischemic damage, which is characterized by early phagocytosis. Tumour necrosis factor alpha (TNF alpha) was increased greatly and significantly in the serum of the pigs that received endotoxin. The lesions described may be the result of both direct damage to muscle fibres by the endotoxin and/or the increased levels of TNF alpha and indirect damage because of the increased diffusion distance, due to the endomysial oedema. The loss of blood proteins into the endomysium may also play a role in generating hypoproteinemia in patients with septic shock.

Animals↗
PubMed2002

BMP signalling: visualisation of the Sog protein gradient.

Extracellular inhibitors are commonly used in development to modulate the activities of signalling molecules. Direct visualisation in the Drosophila embryo of Sog, a Dpp/Scw inhibitor, has now revealed a graded distribution established by degradation and endocytosis.

Animals↗
PubMed1999

The efficacy of collagen dermis membrane and fibrin on cultured epidermal graft using an athymic mouse model.

A human skin substitute consisting of human cultured keratinocytes, collagen dermis, and fibrin was evaluated in athymic mice. Eighty athymic mice were divided randomly into four groups. A 1.5x1.5-cm full-thickness wound defect was created on the back of each athymic mouse under anesthesia. These wounds were covered by sheets of cultured epidermal graft (group A), cultured epidermal graft with collagen dermis and fibrin (group B), cultured epidermal graft with collagen dermis (group C), or cultured epidermal graft with fibrin (group D). The grafts were secured and kept moist by specially designed saline gauze chambers. The take rates of the cultured graft with more than 50% of the wound covered were 65%, 15%, 50%, and 45% respectively. Group B had a significantly lower graft take rate, however the difference was not significant among groups A, C, and D. Light microscopy of biopsies of the grafted sites at 12 days showed complete epithelialization. The incidence of discharge from wound beds in groups A, B, C, and D was 0%, 15%, 15%, and 10% respectively. The results suggest that cultured cells are best grafted directly onto the wound bed or in combination with either a thin layer of collagen or fibrin but not both because the collagen dermal membrane and the fibrin together may impose too great a diffusion barrier for the cultured cell graft to become vascularized.

Animals↗
PubMed1985

Experimental infection of hamsters with Campylobacter jejuni.

Campylobacter jejuni is a major cause of diarrhea and enterocolitis in humans and animals. A mammalian model has been developed for studying pathogenesis of the disease in hamsters by colonizing the ileum and cecum with C. jejuni via either oral intubation after purgation or direct surgical inoculation into the cecum. This colonization resulted in production of disease including diarrhea and intestinal lesions that resembles enterocolitis due to C. jejuni in humans and domestic animals. The mucosal lesions observed grossly at autopsy included erythema of the ileum and cecum and distention of the cecum with fluid. The cecal mucosa was edematous. Epithelial lesions observed by light microscopy included focal edema, occasional hyperplasia, diffuse hyperemia, and infiltration of the lamina propria with leukocytes. C. jejuni-like bacteria penetrated the epithelium and were observed within the lamina propria of infected animals but not in uninfected controls.

Animals↗
PubMed2005

Methods for separating nucleation and growth in protein crystallisation.

The availability of high-quality crystals is crucial to the structure determination of proteins by X-ray diffraction. With the advent of structural genomics the pressure to produce crystals is greater than ever before. Finding favourable conditions for crystallisation is usually achieved by screening of the protein solution with numerous crystallising agents. Optimisation of the crystallisation conditions involves the manipulation of the crystallisation phase diagram with the aim of leading crystal growth in the direction that will produce the desired results. This article highlights recent advances in experimental methods for improving crystal size and quality by separating the nucleation and growth phases of crystallisation using the vapour diffusion and microbatch techniques.

Combinatorial Chemistry Techniques↗
PubMed1967

Studies of cell deformability. IV. A possible role of calcium in cell contact phenomena.

Cells grown in suspension culture were incubated with EDTA-disodium salt and shown to have more easily deformable surfaces and raised electrophoretic mobility than controls, following this treatment. The reversibility of these observations by the addition of calcium ions, and other parallel experiments, support the conclusion that, in these cells, calcium is bound to anionic sites at the cell periphery, some of which are located at the cellular electrokinetic surface. These cells should, therefore, exhibit demonstrable calcium-sensitive aggregation, if current theories on the role of calcium in the physiological situation are correct. The fact that no calcium-sensitive aggregation was observed suggests that calcium does not form "bridges" between the adjacent anionic sites on different cells, and does not act directly by its effects on the diffuse electrical double-layer in this situation. An alternative hypothesis is advanced for the role played by calcium in cell adhesion and separation processes.

Calcium↗
PubMedDate not supplied

[Dynamic aspect of kinetics of reaction catalyzed by lactate dehydrogenase].

The influence of solvent viscosity on the kinetic parameters of the pyruvate reduction reaction catalyzed by lactate dehydrogenase has been investigated. The viscosity was adjusted by sucrose and glycerol solutions at concentrations from 0 to 44% and from 0 to 63%, respectively. The reaction rate decreased abruptly with an increase in viscosity. The study of different reaction stages (enzyme-substrate complex formation, catalysis, inhibitory complex decomposition, competitive inhibition by chlorine ions) revealed that the catalysis (and the related conformational changes) is the only stage (of the above mentioned) that depends markedly on the solvent viscosity. The reaction is insensitive to the changes in the dielectric properties of the solution induced by the addition of alcohols and dioxane. The observed power dependence of the rate constant on viscosity is explained in terms of Kramer's theory which considers the proton transition through the activation barrier to be a diffusion in the field of random forces. The influence of solvent viscosity on enzymic kinetics indicates a direct relation between solvent dynamics and relevant protein conformational movements.

Animals↗
PubMed1986

A theoretical analysis of the effects of plaque thickness and initial salivary sucrose concentration on diffusion of sucrose into dental plaque and its conversion to acid during salivary clearance.

A mathematical model, written in FORTRAN, has been developed to simulate the interrelated processes of salivary sucrose clearance from the mouth, diffusion of sucrose into dental plaque, and conversion of sucrose to acid and glucan. Reaction of acid with enamel is not included in the model. A total of 28 parameters can be varied by the user, and the relative importance of the different factors affecting acid formation can be assessed. The output of the program gives sucrose and acid concentrations and pH at different depths within the plaque. The initial variables studied were plaque thickness, the salivary sucrose concentration, and the duration of exposure of the plaque to sucrose. Stephan curves typical of those recorded in vivo were generated by the model. With any particular salivary sucrose concentration, there was an optimum plaque thickness at which a minimum pH was achieved at the enamel surface, with very thin or thick plaque samples producing a smaller pH fall. With thick plaque, the minimum pH was often not achieved at the inner surface but at some intermediate depth, which may explain the location of early caries lesions in fissures. The extent of the pH fall at the inner surface and the duration of the pH-minimum region of the Stephan curve were directly related to the initial salivary sucrose concentration and to the duration of exposure to sucrose prior to normal salivary clearance. Simulation of a water rinse at as short a time as two min after the beginning of normal salivary sugar clearance showed that this procedure had only a very small effect on the shape of the Stephan curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed2003

Calibrated latex microspheres percolation: a possible route to model endodontic bacterial leakage.

Endodontic therapy is conducted to effectively seal the root canal system. In vitro methods are used to estimate the quality of the seal, generally by measuring any microleakage that allows the tracers to penetrate along the obturated root canal. The use of bacteria as tracers seems to give the most clinically relevant demonstration of microleakage associated with a root canal system. Many bacterial strains have been used to evaluate marginal leakage, but results are sometimes contradictory, probably because they may depend on the bacterial strain used. In the studies described in this article, the percolation of both calibrated latex microspheres equivalent in diameter (0.4-9.5 microm) to bacteria and three bacterial strains (Actinomyces odontolyticus, Lactobacillus acidophilus, and Pseudomonas fluorescens) was compared in teeth filled using noncompressive and compressive techniques. The depth (d) to which the microspheres and bacteria penetrated varied over the time (t) of contamination according to a logarithmic relation. The slope (S) and the intercept (I, corresponding to penetration after 1 month) of the d = f(In t) plots can serve to quantify penetration over time. Statistical analysis of I by the Newman-Keuls procedure, which couples the tracers and filling techniques, showed that A. odontolyticus and L. acidophilus behave like 4.8-microm particles and P. fluorescens like 2.2-microm particles (corresponding approximately to their size in length) and that noncompressive techniques are less hermetic than compressive techniques. S and I are in direct relation and this relation is independent of the filling technique. Moreover, for the calibrated particles, both I and S varied linearly with the inverse of the square root of the particle diameter, indicating that their displacements are governed solely by Brownian movements and the penetration over time is caused by diffusion phenomena. The size of the tracer is the predominant factor governing its penetration. Inert particles mimic bacterial percolation into the marginal hiatus and can thus be used to model this percolation and establish a relative scale of the behavior of different bacteria during percolation.

Actinomyces↗
PubMed1994

Magnetization transfer, cross-relaxation, and chemical exchange in rotationally immobilized protein gels.

Water proton spin-lattice relaxation rates are reported as a function of the magnetic field strength for cross-linked bovine serum albumin samples. The relaxation dispersion profile is analyzed using a relaxation model where the solid components have the magnetic field dependence proportional to v-0.5 which may result from a defect diffusion model with two degrees of freedom. If the cross-linking agent concentration is not sufficiently high, the relaxation dispersion curve may have significant contributions from freely rotating protein. The magnetic field dependence of the relaxation rates studied as a function of the proton mole fraction in the sample show that approximately 30% of the magnetization transfer rate is directly proportional to the proton mole fraction. This contribution is identified with the magnetization transfer from exchange of whole water molecules with buried binding sites on the protein. The second order magnetization transfer rate constant is 388 s-1 assuming unit water spin concentration. The solid component relaxation obeys an Arrhenius activation law, but the overall temperature dependence of the cross-relaxation is complicated by chemical exchange processes which enter with opposite sign.

Animals↗
PubMed1992

Intraneoplastic application of metrizamide-containing liposomes: kinetic studies with computed tomography.

Liposomes may serve as drug carriers not only for systemic chemotherapy but also for intraneoplastic drug therapy because they show a sustained drug release. In the present study, the in vivo kinetics of intraneoplastic deposits of large multilamellar vesicles containing metrizamide was followed up in a rat tumor model with computed tomography. The influence of four different lipid compositions on the retardation capacity of large multilamellar liposomes was investigated. By comparing the dynamic data of X-ray attenuation and volume of liposome deposits, a rank order for the in vivo stability of metrizamide containing multilamellar vesicles could be established: the least stable liposomes were made of pure dimyristoyl-phosphatidyl-choline, the most stable type was made of equimolar parts of stearoyl-palmitoyl-phosphatidyl-choline and cholesterol. Of intermediate stability were liposomes made of equimolar parts of dimyristoyl-phosphatidyl-choline and cholesterol, and those made of pure stearoyl-palmitoyl-phosphatidyl-choline. The addition of 50% cholesterol increased the membrane stability of both dimyristoyl-phosphatidyl-choline and stearoyl-palmitoyl-phosphatidyl-choline liposomes. No diffusion of large multilamellar liposomes away from the injection site was observed. The in vivo stability of the liposomes was considerably less than that observed in vitro, suggesting active degradation processes. It is concluded that large, multilamellar liposomes may be suitable carriers for intraneoplastic chemotherapy. The present model is easily adaptable to be transferred into clinical conditions, and may allow direct monitoring of intraneoplastic liposome-mediated chemotherapy in human brain tumors.

Animals↗
PubMed1983

Actions of opiates, substance P, and serotonin on the excitability of primary afferent terminals and observations on interneuronal activity in the neonatal rat's dorsal horn in vitro.

Approximately 5 segments of lumbo-thoracic spinal cord together with connected dorsal root ganglia were removed from 1-11-day-old rats and maintained in vitro. Dorsal root afferents, recorded from the ganglion and stimulated at the root entry zone, had conduction velocities typical of unmyelinated fibers (less than 2 m/s). The spinal terminals of individual afferents showed increased excitability with bath application of substance P and serotonin and decreased excitability with morphine sulfate, [D-ala2]methionine-enkephalinamide, manganese ions and magnesium ions. Naloxone by itself elicited no change in excitability, although it appeared to reduce the ongoing effect of opiates. Neurons recorded extracellularly in the dorsal horn responded to afferent volleys with one or more of 3 distinct phases: an excitation roughly coincident with the volley's arrival, a 50-300 ms period of inhibition, and a late excitation of 150-300 ms latency. The excitability results are accounted for by a model in which substance P, gamma-aminobutyric acid and possibly other depolarizing agents are contained in interneurons which synapse on afferent terminals. These interneurons could receive inhibitory enkephalinergic input, and, in the neonate but not the adult, excitatory serotoninergic input. An alternate scheme would have enkephalin and serotonin acting directly on afferent terminals, although perhaps by non-synaptic diffusion since the appropriate synapses have not been seen in histochemical studies. Such an action for enkephalin might explain the existence of opiate receptor on afferent terminals. The interneuronal responses to afferent volleys are parallel in most aspects to those found in the dorsal horns of adult mammals in vivo.

Afferent Pathways↗