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PubMed1995

Heating characteristics of the TRIPAS hyperthermia system for deep seated malignancy.

A deep heating hyperthermia device TRIPAS (a triapplicator system) consisting of three independent, dielectrically loaded horn applicators operating in phase at 300 MHz was investigated. The heating characteristics produced by this hyperthermia system were analyzed by means of thermochromic liquid-crystal cards and a modified CDRH (Center for Devices and Regulatory Health) elliptical phantom. Both homogenous and inhomogeneous phantoms were used, simulating high and low permittivity tissues (muscle and lung). These equivalent tissues were made of polyacrylamide gel. The semiquantitative heating pattern analysis showed a central heating of 1/3 of maximum heating at a depth of 10 cm in both homogenous (muscle) and heterogenous (muscle/fat) phantoms. Also more uniform temperature/SAR distributions were generated in muscle equivalent material than those in lung.

Acrylic Resins↗

PubMed2002

Cellular and molecular regulation of vaccination with heat shock protein 60 from Histoplasma capsulatum.

Vaccination with heat shock protein 60 (Hsp60) from Histoplasma capsulatum induces a protective immune response in mice. We explored the cellular and molecular requirements for the efficacy of recombinant Hsp60 in mice. Depletion of CD4(+), but not CD8(+), cells during the inductive phase of vaccination abolished protection, as assessed by survival and by the fungal burden in lungs and spleens. In the expressive phase, the elimination of CD4(+) or CD8(+) cells after immunization did not significantly alter fungal recovery or survival from a lethal challenge. Depletion of both subpopulations after Hsp60 vaccination resulted in a failure to control a lethal infection and a higher fungal burden in lungs and spleens. Cytokine release by spleen cells from mice vaccinated with Hsp60 produced substantially more gamma interferon and interleukin-10 and -12 than that of cells from mice immunized with either H. capsulatum recombinant Hsp70 or bovine serum albumin. The generation of gamma interferon, but not of interleukin-10, was dependent on T cells, in particular CD4(+) cells. Treatment of Hsp60-immunized mice with monoclonal antibody to gamma interferon or interleukin-10 or -12 in the inductive phase of vaccination was accompanied by increased recovery of yeast cells from lungs and spleens and 100% mortality. Likewise, the neutralization of gamma interferon or interleukin-12 abolished the protective effect of Hsp60 in the expressive phase. These results delineate the complexity of the regulatory elements necessary for vaccination against this fungus.

Animals↗

PubMed2006

Proton in the well and through the desolvation barrier.

The concept of the membrane proton well was suggested by Peter Mitchell to account for the energetic equivalence of the chemical (DeltapH) and electrical (Deltapsi) components of the proton-motive force. The proton well was defined as a proton-conducting crevice passing down into the membrane dielectric and able to accumulate protons in response to the generation either of Deltapsi or of DeltapH. In this review, the concept of proton well is contrasted to the desolvation penalty of > 500 meV for transferring protons into the membrane core. The magnitude of the desolvation penalty argues against deep proton wells in the energy-transducing enzymes. The shallow DeltapH- and Deltapsi-sensitive proton traps, mechanistically linked to the functional groups in the membrane interior, seem more realistic. In such constructs, the draw of a trapped proton into the membrane core can happen at the expense of some exergonic reaction, e.g., release of another proton from the membrane into the aqueous phase. It is argued that the proton transfer in the ATP synthase and the cytochrome bc complex could proceed in this way.

Biological Transport↗

PubMed1983

Quantitative relations between color-opponent response of horizontal cells and action spectra of cones.

1. Relations between cones and chromatic-type horizontal cells (C-cells) were investigated by intracellular recording in the retina of the walleye (Stizostedion vitreum). 2. The retina contains two classes of cones, midwave (M) and long wave (L). Their action spectra have maximum sensitivity at 533 and 605 nm, respectively, and have been measured with good precision from 400 to 750 nm. 3. C-cells generate relatively sustained depolarizing and hyperpolarizing responses to deep red (680 nm) and green (530 nm) test flashes, respectively, but prominent on and off transients are evoked by intermediate wavelengths. To minimize these temporal interactions, quantitative analysis was restricted to measurements of the apparent steady-state response amplitude. 4. Response amplitude was linearly related to flash intensity for responses that did not exceed 20% of their respective maxima. This is called the linear range. At higher levels, the nonlinear region of the Naka-Rushton relation holds approximately if input is largely confined to the hyperpolarizing or depolarizing mechanism. 5. Tests with red/green mixture flashes show that the hyperpolarizing and depolarizing inputs interact by simple summation for responses in the linear range. At higher levels, the interaction is complex. 6. Spectral-response curves (response amplitude versus wavelength for flashes of equal photon level) were determined for 16 C-cells in the linear range. The exact form of these curves varied considerably from cell to cell, reflecting differences in the relative strength of the hyperpolarizing and depolarizing mechanisms. 7. The spectral-response curves were analyzed by a simple linear model based on the action spectra of the L and M cones. Measured and predicted spectral-response curves agree closely. The only free parameter in the analysis is a scaling factor that specifies the strength of the L cone input relative to the M cone input. 8. Triphasic spectral-response curves, as predicted by the model, were found in the sauger (Stizostedion canadense). These C-cells have short-wavelength responses due to input from long-wave cones, resemble certain triphasic cells in primate retina, and differ sharply from other triphasic C-cells found in other fish retinas. 9. Although the precise synaptic mechanisms must still be identified, the present results show that the functional information transfer from cones to C-cells in the linear range can be closely approximated by simple operations of scaling, sign inversion, and simple summation. The C-cell thus effectively subtracts one cone action spectrum from the other and displays the difference in the form of the spectral-response curve.

Animals↗

PubMed1982

Nonlinear feedback model of neuronal populations in hippocampal CAl region.

1. A lumped-circuit model is proposed for the local interactions within the hippocampal CAl region. Each neuronal population is represented by a linear differential equation or a linear transfer function in the Laplace domain. Interactions between neuronal populations are represented by gain factors. Recurrent inhibition of pyramidal cells by the inhibitory interneurons is the important interaction represented by an asymmetric, bidirectionally saturating gain curve. The inputs to the model are orthodromic or antidromic inputs to the pyramidal cells and a tonic input from the brain stem. The outputs are the response ot pyramidal cells and interneurons. 2. The model is evaluated by data of intracellular and extracellular recordings from the hippocampus. Extracellular recordings consist of the average evoked potentials (AEPs), unitary poststimulus time histograms (PSTHs), and the spontaneous electroencephalogram (EEG). On account of the regular structure of the hippocampus, extracellular potentials are expected to correspond to the average intracellular potential among a local neuronal population. 3. Under deep anesthesia, all neuronal responses evoked by an electrical shock to the hippocampal afferents end in a prolonged inhibition of pyramidal cells. The model further predicts that the duration of inhibition increases with stimulus intensity, which is verified experimentally. 4. In the awake rat, especially during behaviors accompanied by a hippocampal theta rhythm (e.g., walking), the AEPs evoked by stimulation of afferent input to the CAl region were oscillatory with a frequency of 20-50 cycles/s. In the model an excitatory bias from the brain stem is assumed to linearize the local circuits, resulting in oscillatory responses similar to those obtained experimentally. 5. As observed by spectral analysis, the hippocampal EEG of the frequency 40-70 Hz varied in power and resonance during various behaviors of the rat. Except for the theta rhythm, analysis of the output(s) of the model given a Gaussian white-noise input showed similar power spectra as the EEG in vivo. The increase in power of the 40-70 Hz EEG in some behaviors, e.g., walking, is reproduced by assuming that during such behaviors a modulating bias from the brain stem linearizes the local CAl circuits. This latter circumstances underlies the generation of oscillatory AEPs and the high-frequency EEG. 6. When recurrent excitatory-inhibitory feedback is very large, the model produces a limit cycle of 50-65 cycles/s. The limit cycle is suggested to be the cause of a particular type of high-frequency (50-65 cycles/s) hippocampal afterdischarge that occurs after tetanization of the input pathways. The amplitude, frequency, and waveform of the model generated and experimental data are similar. 7. In conclusion, a nonlinear recurrent excitatory-inhibitory feedback model of the hippocampus explains and integrates various existing experimental data. The model further predicts results that can be experimentally tested.

Action Potentials↗

PubMed2000

Plateau potential-dependent windup of the response to primary afferent stimuli in rat dorsal horn neurons.

In the spinal cord, repetitive stimulation of nociceptive afferent fibres induces a progressive build-up of dorsal horn neuron (DHN) responses. This 'action potential windup' is used as a cellular model of central sensitization to pain. It partly relies on synaptic plasticity, being reduced after blocking NMDA and neurokinin receptors. Using intracellular recordings in a slice preparation of the rat spinal cord, we have analysed the implication of an additional non-synaptic component of windup. Primary afferent fibres were electrically stimulated in the dorsal root. Of 47 responding deep DHNs, 17 (36%) produced action potential windup and afterdischarge during consecutive periods of repeated stimuli (0.4-1 Hz) activating high- (n = 13 neurons) and low-threshold (n = 6 neurons) afferent fibres. When the NMDA receptors were blocked, the rate of windup did not change. In all neurons, there was an absolute correlation between expression of windup and the production of calcium-dependent plateau potentials. Sensitization of the DHN response, similar to the synaptically induced windup, was obtained by repetitive intracellular injection of depolarizing current pulses. This intracellularly induced windup had the same pharmacology as the plateau potential. Synaptically induced windup was also abolished by nifedipine, an L-type calcium-channel blocker. Expression of plateau properties in DHNs is therefore a critical component of windup, operating downstream of synaptic processes. Being associated with calcium influx, generation of plateau potentials could be a link between short-term plasticity and the long-term modification of DHN excitability associated with central sensitization.

2-Amino-5-phosphonovalerate↗

PubMed2004

Testing species boundaries in an ancient species complex with deep phylogeographic history: genus Xantusia (Squamata: Xantusiidae).

Identification of species in natural populations has recently received increased attention with a number of investigators proposing rigorous methods for species delimitation. Morphologically conservative species (or species complexes) with deep phylogenetic histories (and limited gene flow) are likely to pose particular problems when attempting to delimit species, yet this is crucial to comparative studies of the geography of speciation. We apply two methods of species delimitation to an ancient group of lizards (genus Xantusia) that occur throughout southwestern North America. Mitochondrial cytochrome b and nicotinamide adenine dinucleotide dehydrogenase subunit 4 gene sequences were generated from samples taken throughout the geographic range of Xantusia. Maximum likelihood, Bayesian, and nested cladogram analyses were used to estimate relationships among haplotypes and to infer evolutionary processes. We found multiple well-supported independent lineages within Xantusia, for which there is considerable discordance with the currently recognized taxonomy. High levels of sequence divergence (21.3%) suggest that the pattern in Xantusia may predate the vicariant events usually hypothesized for the fauna of the Baja California peninsula, and the existence of deeply divergent clades (18.8%-26.9%) elsewhere in the complex indicates the occurrence of ancient sundering events whose genetic signatures were not erased by the late Wisconsin vegetation changes. We present a revised taxonomic arrangement for this genus consistent with the distinct mtDNA lineages and discuss the phylogeographic history of this genus as a model system for studies of speciation in North American deserts.

Animals↗

PubMed2000

Search and discovery strategies for biotechnology: the paradigm shift.

Profound changes are occurring in the strategies that biotechnology-based industries are deploying in the search for exploitable biology and to discover new products and develop new or improved processes. The advances that have been made in the past decade in areas such as combinatorial chemistry, combinatorial biosynthesis, metabolic pathway engineering, gene shuffling, and directed evolution of proteins have caused some companies to consider withdrawing from natural product screening. In this review we examine the paradigm shift from traditional biology to bioinformatics that is revolutionizing exploitable biology. We conclude that the reinvigorated means of detecting novel organisms, novel chemical structures, and novel biocatalytic activities will ensure that natural products will continue to be a primary resource for biotechnology. The paradigm shift has been driven by a convergence of complementary technologies, exemplified by DNA sequencing and amplification, genome sequencing and annotation, proteome analysis, and phenotypic inventorying, resulting in the establishment of huge databases that can be mined in order to generate useful knowledge such as the identity and characterization of organisms and the identity of biotechnology targets. Concurrently there have been major advances in understanding the extent of microbial diversity, how uncultured organisms might be grown, and how expression of the metabolic potential of microorganisms can be maximized. The integration of information from complementary databases presents a significant challenge. Such integration should facilitate answers to complex questions involving sequence, biochemical, physiological, taxonomic, and ecological information of the sort posed in exploitable biology. The paradigm shift which we discuss is not absolute in the sense that it will replace established microbiology; rather, it reinforces our view that innovative microbiology is essential for releasing the potential of microbial diversity for biotechnology penetration throughout industry. Various of these issues are considered with reference to deep-sea microbiology and biotechnology.

Biotechnology↗

PubMed1986

Segmental cable modelling of electrotonic transfer properties of deep superior colliculus neurons in the cat.

A segmental cable model of tecto-reticulo-spinal neurons of cat superior colliculus was constructed, based on detailed anatomical measurements from three neurons. The calculated membrane resistance for which the model best fitted the measured input resistance was 2,300-3,000 omega cm2. Electrotonic length of dendrites fell under 0.59-1.20 and 0.52-1.05 length constants, while the mean electrotonic length for the three cells averaged 0.91, 0.79, 0.81 and 0.80, 0.70, 0.71 (for sealed-end and open-end cable termination, respectively). Dendrite-to-soma conductance ratios averaged 16.0, 10.7, 7.5 and 21.3, 14.1, 11.4 for the two different end conditions, respectively. Synaptic efficacy was estimated by the transfer of steady-state voltage or current reaching the soma from distal dendritic locations. While voltage transfer was less than 1%, almost 60% of injected current (or charge) reached the soma. Analysis of voltage transients recorded experimentally in TRSNs demonstrated considerable difference between parameters derived from either equivalent-cylinder model or segmental cable model. The obvious deviations of TRSNs both in anatomical and electrotonic respect from the assumptions of the equivalent-cylinder model indicate that the detailed cable model will give a more appropriate description of these neurons. The significance of the estimated electrotonic parameters for the particular burst generation mechanism of TRSNs is discussed.

Animals↗

PubMed1997

SIMS: computation of a smooth invariant molecular surface.

SIMS, a new method of calculating a smooth invariant molecular dot surface, is presented. The SIMS method generates the smooth molecular surface by rolling two probe spheres. A solvent probe sphere is rolled over the molecule and produces a Richards-Connolly molecular surface (MS), which envelops the solvent-excluded volume of the molecule. In deep crevices, Connolly's method of calculating the MS has two deficiencies. First, it produces self-intersecting parts of the molecular surface, which must be removed to obtain the correct MS. Second, the correct MS is not smooth, i.e., the direction of the normal vector of the MS is not continuous, and some points of the MS are singular. We present an exact method for removing self-intersecting parts and smoothing the singular regions of the MS. The singular MS is smoothed by rolling a smoothing probe sphere over the inward side of the singular MS. The MS in the vicinity of singularities is replaced with the reentrant surface of the smoothing probe sphere. The smoothing method does not disturb the topology of a singular MS, and the smooth MS is a better approximation of the dielectric border between high dielectric solvent and the low dielectric molecular interior. The SIMS method generates a smooth molecular dot surface, which has a quasi-uniform dot distribution in two orthogonal directions on the molecular surface, which is invariant with molecular rotation and stable under changes in the molecular conformation, and which can be used in a variety of implicit methods of modeling solvent effects. The SIMS program is faster than the Connolly MS program, and in a matter of seconds generates a smooth dot MS of a 200-residue protein. The program is available from the authors on request (see http:@femto.med.unc.edu/SIMS).

Algorithms↗

PubMed1996

Immunodetection of cytoskeletal structures and the Eg5 motor protein on deep-etch replicas of Xenopus egg cortices isolated during the cortical rotation.

We have developed a new method for immunogold detection on deep-etch replicas of isolated Xenopus egg cortices in order to examine the interactions of different cortical elements in three dimensions at high resolution. We have applied this technique to vegetal cortices isolated during the second half of the first cell cycle. The vegetal cortical region at this time is the site of cellular machinery responsible for the 'cortical rotation'. The entire cortex translocates with respect to the inner cytoplasm, relocating dorsalising determinants to the future dorsal side of the egg. The aligned microtubules in the shear zone between cytoplasm and cortex, implicated in the cortical rotation, were found to be organised as interweaving loose bundles. Interleaved amongst these aligned microtubules were extensive sheets of ER lying in layers parallel to the egg surface. Cytokeratin filaments were found to associate closely with the microtubules over short stretches. Putative actin filaments were present in the shear zone and in the cortex. Eg5, an abundant kinesin-related microtubule motor protein, and candidate for a role in generating cortical rotation movement, showed an almost exclusive localisation to microtubules. Immunofluorescence studies of cortices treated with detergent to disrupt ER or cold to depolymerise microtubules confirmed that Eg5 associates primarily with microtubules. We propose revised models for the mechanism of cortical rotation based on these observations and conclude that Eg5 is unlikely to move ER relative to microtubules during the cortical rotation.

Animals↗

PubMed2006

Effects of a manual therapy technique in experimental lateral epicondylalgia.

In patients with lateral epicondylalgia, mobilization-with-movement (MWM) is used as an intervention aimed at achieving analgesia and enhancing grip force, although the mechanisms underlying these effects are unclear. The present study investigated the acute sensory and motor effects of an MWM intervention in healthy controls with experimentally induced lateral epicondylalgia. Twenty-four subjects were randomly allocated to either a MWM or a placebo group (n=12). In both groups, to generate the model of lateral epicondylalgia, delayed onset muscle soreness (DOMS) was provoked in one arm 24h prior (Day 0) to hypertonic saline-induced pain in the extensor carpi radialis brevis muscle (Day 1). Either a MWM or placebo intervention was applied during the saline-induced pain period. Saline-induced pain intensity (visual analogue scale: VAS), pain distribution and pain quality were assessed quantitatively. Pressure pain thresholds (PPTs) were recorded at the common extensor origin and the extensor carpi radialis brevis muscle. Maximal measures of grip and wrist extension force were recorded. In both groups (pooled data), DOMS was efficiently induced as demonstrated by a significant decrease in pre-exercise to pre-injection PPT at the common extensor origin (-45+/-19%) and at the extensor carpi radialis brevis (-61+/-23%; P<0.05), and a significant decrease in maximal grip force (-25+/-6%) and maximal wrist extension force (-40+/-12%; P<0.001). Moreover, both groups experienced a significant increase in muscle soreness (3.9+/-0.2; P<0.0001) at Day 1 compared to pre-exercise. During saline-induced pain and in response to intervention, there were no significant between-group differences in VAS profiles, pain distributions, induced deep tissue hyperalgesia or force attenuation. These data suggest that the lateral glide-MWM does not activate mechanisms associated with analgesia or force augmentation in subjects with experimentally induced features simulating lateral epicondylalgia.

Adult↗

PubMed1996

The anticonvulsant action of fluoxetine in substantia nigra is dependent upon endogenous serotonin.

Fluoxetine, a serotonin (5-HT) reuptake inhibitor, has been documented to exert a protective action against convulsive seizures in animal models, when administered either systemically, or focally into substantia nigra. It is likely that the mechanism of anticonvulsant action of fluoxetine is due to an enhancement of endogenous 5-HT transmission. To evaluate this possibility in the context of the anticonvulsant action of intranigral fluoxetine, we examined the influence of 5-HT-mediated transmission in substantia nigra on seizure susceptibility in a rat model of focally evoked complex partial seizures. In addition to fluoxetine (3.5 nmol), we found that the directly acting 5-HT receptor agonists, 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (10 nmol), 1-(3-chlorophenyl)piperazine (m-CPP) (7.4 nmol), gepirone (70 nmol) and 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) (10 nmol), when microinjected bilaterally into substantia nigra, protected rats from limbic motor seizures evoked focally from area tempestas, an epileptogenic site in the deep rostral piriform cortex. This indicates that multiple 5-HT receptor subtypes in substantia nigra may contribute to seizure regulation. Consistent with this, the 5-HT antagonist, metergoline, partially reversed the anticonvulsant action of intranigral fluoxetine. Depletion of endogenous 5-HT, by pretreatment with parachlorophenylalanine (PCPA), completely prevented the anticonvulsant action of intranigral fluoxetine, without modifying the anticonvulsant effect of intranigral TFMPP. These findings support the proposal that the anticonvulsant action of fluoxetine in substantia nigra is due to an enhancement of the synaptic action of endogenous 5-HT in substantia nigra which in turn is mediated via multiple 5-HT receptors. Endogenous 5-HT transmission in substantia nigra is therefore capable of limiting the development and propagation of seizure activity generated in limbic circuits.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2006

Evolution of helotialean fungi (Leotiomycetes, Pezizomycotina): a nuclear rDNA phylogeny.

The highly divergent characters of morphology, ecology, and biology in the Helotiales make it one of the most problematic groups in traditional classification and molecular phylogeny. Sequences of three rDNA regions, SSU, LSU, and 5.8S rDNA, were generated for 50 helotialean fungi, representing 11 out of 13 families in the current classification. Data sets with different compositions were assembled, and parsimony and Bayesian analyses were performed. The phylogenetic distribution of lifestyle and ecological factors was assessed. Plant endophytism is distributed across multiple clades in the Leotiomycetes. Our results suggest that (1) the inclusion of LSU rDNA and a wider taxon sampling greatly improves resolution of the Helotiales phylogeny, however, the usefulness of rDNA in resolving the deep relationships within the Leotiomycetes is limited; (2) a new class Geoglossomycetes, including Geoglossum, Trichoglossum, and Sarcoleotia, is the basal lineage of the Leotiomyceta; (3) the Leotiomycetes, including the Helotiales, Erysiphales, Cyttariales, Rhytismatales, and Myxotrichaceae, is monophyletic; and (4) nine clades can be recognized within the Helotiales.

Ascomycota↗

PubMed1999

Y-chromosome-specific microsatellite mutation rates re-examined using a minisatellite, MSY1.

Polymorphic Y-chromosome-specific microsatellites are becoming increasingly used in evolutionary and forensic studies and, in particular, in dating the origins of Y-chromosomal lineages. Previously, haplotyping of Y chromosomes from males belonging to a set of deep-rooting pedigrees was used to estimate a conservative average Y-chromosomal microsatellite mutation rate of 2.1 x 10(-3)per locus per generation. A number of males showed multiple differences in haplotypes compared with other males within their pedigrees, and these were excluded from the calculation of this estimate, on the grounds that non-paternity was a more probable explanation than multiple mutation within a lineage. Here we reanalyse the pedigrees using an independent highly polymorphic system, the Y-specific minisatellite, MSY1. This supports the hypothesis of non-paternity where more than one microsatellite difference was observed, provides further support for the previously deduced microsatellite mutation rate and throws light on the mutation dynamics of MSY1 itself, suggesting that single-step changes are not the only mode of mutation.

Genetic Markers↗

PubMed2005

Surgeon and hospital volume and the management of colorectal cancer patients in Australia.

BACKGROUND: The evidence for a relationship between patient outcomes and clinician and hospital volume is increasing. The National Colorectal Cancer Care Survey was undertaken to determine the management patterns in Australia for individuals newly diagnosed with colorectal cancer in a 3 month period in the year 2000. METHODS: All new cases of colorectal cancer registered at each Australian State Cancer Registry were entered into the survey. This generated a questionnaire that was sent to the treating surgeon. Chi-squared tests and logistic regression analyses were used to determine levels of statistical significance. RESULTS: Of 2,383 surgical questionnaires generated, 2,015 (85%) were completed. The majority (58%) of surgeons treated one or two patients with colorectal cancer over the 3 months of the survey. There was variation across surgeon cohorts for preoperative measures including the use of deep vein thrombosis prophylaxis. Patients seen by low volume surgeons were most likely to be given a permanent stoma (P < 0.0001). Patients with rectal cancer who were operated on by high volume surgeons were significantly more likely to receive a colonic pouch (P < 0.0001). CONCLUSION: This nationwide population-based survey of the treatment of colorectal cancer patients suggests that the delivery of care by surgeons (the majority) who treat patients with rectal cancer infrequently should be evaluated.

Adolescent↗

PubMed1993

Potential distributions generated by point stimulation in a myocardial volume: simulation studies in a model of anisotropic ventricular muscle.

INTRODUCTION: We present simulations of extracellular potential patterns elicited by delivering ectopic stimuli to a parallelepipedal slab of ventricular tissue represented as an anisotropic bidomain incorporating epi-endocardial fiber rotation. METHODS AND RESULTS: Simulations were based on an eikonal model that determines wavefront shapes throughout the slab at every time instant during the depolarization phase, coupled with an approximate model of the action potential profile. The endocardial face of the slab was in contact with blood and the composite volume was surrounded by an insulating medium. The effect of a simplified Purkinje network was also studied. RESULTS: (1) For all pacing depths, except endocardial pacing, a central negative area and two potential maxima were observed at QRS onset in all intramural planes parallel to the epicardium. In all planes, the axis joining the two maxima was approximately aligned with the direction of fibers in the plane of pacing. Endocardial pacing generated a different pattern, but only when blood was present; (2) During later stages of excitation, outflowing currents (from the wavefront toward the resting tissue) were always emitted, at all intramural depths, only from those portions of the wavefront that spread along fibers. At any given instant, the position of the two potential maxima in a series of planes parallel to the epicardium and intersecting the wavefront rotated as a function of depth, following the rotating direction of intramural fibers. Purkinje involvement modified the above patterns. CONCLUSION: Epicardial and endocardial potential maps provided information on pacing site and depth and on subsequent intramural propagation by reflecting the clockwise or counter-clockwise rotation of the deep positivity. Results may be applicable to epicardial and endocardial potential maps recorded at surgery or from endocavitary probes.

Action Potentials↗

PubMed2002

Stilbazulenyl nitrone, a novel azulenyl nitrone antioxidant: improved neurological deficit and reduced contusion size after traumatic brain injury in rats.

OBJECT: Stilbazulenyl nitrone (STAZN) is a second-generation azulenyl nitrone that has markedly enhanced antioxidant properties compared with those of conventional alpha-phenyl nitrones. In this study, the authors assessed the potential efficacy of STAZN in a rodent model of fluid-percussion brain injury, which results in a consistent cortical contusion. METHODS: After anesthesia had been induced in normothermic Sprague-Dawley rats (brain temperature 36-36.5 degrees C) by halothane-nitrous oxide, the animals were subjected to a right parietooccipital parasagittal fluid-percussion injury (1.5-2 atm). The agent (STAZN, 30 mg/kg: eight animals) or vehicle (dimethyl sulfoxide; eight animals) was administered intraperitoneally at 5 minutes and 4 hours after trauma. The neurological status of each rat was evaluated on Days 1, 2, and 7 postinjury (normal score 0, maximum injury 12). Seven days after trauma, the rat brains were perfusion fixed, coronal sections at various levels were digitized, and areas of contusion were measured. Treatment with STAZN significantly improved neurological scores on Days 2 and 7 postinjury compared with vehicle-treated rats. Administration of STAZN also significantly reduced the total contusion area by 63% (1.8 +/- 0.5 mm2 in STAZN-treated animals compared with 4.8 +/- 2.1 mm2 in vehicle-treated animals; p = 0.04) and the deep cortical contusion area by 60% (1.2 +/- 0.2 mm2 in STAZN-treated animals compared with 2.9 +/- 1.2 mm2 in vehicle-treated animals; p = 0.03). By contrast, hippocampal cell loss in the CA3 sector was unaffected by STAZN treatment. CONCLUSIONS: Therapy with STAZN, a novel potent antioxidant, administered following traumatic brain injury, markedly improves neurological and histological outcomes. Azulenyl nitrones appear to represent a promising class of neuroprotective agents for combating this devastating condition.

Animals↗