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Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results.

Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The tumoricidal effect was related to the mTHPC dose, light dose and the time interval between sensitation and activation. 0.3 mg kg-1 mTHPC activated after 48 h with 10 Joules cm-2 of non-thermal laser light at 650 nm resulted in a 10 mm deep tumour infarction, due to tumour vessel necrosis and thrombosis. The mTHPC tissue concentration was up to 14 times higher in the tumour than in normal tissues. Skin photosensitivity was mild, dose dependent and occurred 3 to 10 days after administration of mTHPC. According to the results obtained, intraoperative mTHPC-PDT was performed following pleuropneumonectomy in two, pleurectomy and lobectomy in one and pleurectomy in one patient. Ten Joules cm-2 were delivered to the diaphragm and the costophrenic sulcus and 5 Joules cm-2 to the remaining thoracic cavity. The postoperative course was marked by loss of appetite, fluid retention, hypoproteinemia and severe chest pain. One patient succumbed from aspiration pneumonia. The remaining patients developed no neural or vascular alterations and no bronchial stump insufficiency during follow-up. mTHPC-PDT following surgical tumour resection deserves further evaluation in good risk patients with diffuse malignant mesothelioma.

Combined Modality Therapy↗

Evolution of morphology in UHMWPE following accelerated aging: the effect of heating rates.

Accelerated aging methods are used to evaluate the oxidative stability of UHMWPE components for total joint replacements. In this study, we traced the evolution of the crystalline morphology during accelerated thermal aging of UHMWPE in air with the intent of explaining previous, counterintuitive heating rate effects. GUR4150HP extruded rod stock material was machined into miniature (0.5 mm thick) specimens that were either gamma irradiated in air or in nitrogen (27 +/- 3 kGy) or left unirradiated (control). Accelerated aging in an air furnace (at 80 degrees C, atmospheric pressure) was performed on half of the test samples at a heating rate of 0.1 degrees C/min and at 5 degrees C/min for the remaining half. Although the initial heating rate, as measured by changes in density, did influence the absolute degradation rate by up to 214%, the heating rate effect did not appear to influence the relative ranking of UHMWPE in terms of its oxidative stability. The heating rate effect is more consistent with a kinetic mechanism of the oxidation process than it is with a previously hypothesized diffusion mechanism. UHMWPE morphology, as characterized using a transmission electron microscope (TEM), demonstrated considerable rearrangement of the crystalline regions as a result of the accelerated aging. The stacking of the lamellae observed after accelerated aging was not consistent with the morphology of naturally aged UHMWPE components. The observed differences in crystalline morphology likely result from the enhanced mobility of the polymer chains due to thermal aging and may be analogous to an annealing process.

Algorithms↗

Modeling growth from the vapor and thermal annealing on micro- and nanopatterned substrates.

We propose a -dimensional mesoscopic model to describe the most relevant physical processes that take place while depositing and/or annealing micro- and nanopatterned solid substrates. The model assumes that a collimated incident beam impinges over the growing substrate; scattering effects in the vapor and reemission processes are introduced in a phenomenological way as an isotropic flow. Surface diffusion is included as the main relaxation process at the micro- or nanoscale. The stochastic model is built following population dynamics considerations; both stochastic simulations and the deterministic limit are analyzed. Numerical aspects regarding its implementation are also discussed. We study the shape-preserving growth mode, the coupling between shadowing effects and random fluctuations, and the spatial structure of noises using numerical simulations. We report important deviations from linear theories of surface diffusion when the interfaces are not compatible with the small slope approximation, including spontaneous formation of overhangs and nonexponential decay of pattern amplitudes. We discuss the dependence of stationary states with respect to the boundary conditions imposed on the system.

Journal Article↗

[The thermally induced transformation of the protein-detergent complexes of the Na+,K(+)-ATPase catalytic subunits of the kidneys and brain in PAG electrophoresis].

Electrophoretic properties of the protein bands of Na+, K(+)-ATPase catalytic subunits of the kidney and brain have been comparatively studied for some types of animals after heat treatment of the preparations in the presence of DS-Na. The diffuse protein zone with lower electrophoretic mobility after heat-induced conformational transformation of alpha appears on gels parallel with protein band alpha II which is typical of this process. The prolonged heat treatment causes more rapid electrophoretic degradation of the alpha-isoform of the Na+, K(+)-ATPase catalytic subunit of the brain in comparison with alpha +. The results of the investigations are discussed in the aspect of existence of heat-induced transformation of the protein-detergent complexes of catalytic subunits of the enzyme.

Animals↗

A DNA hairpin with a single residue loop closed by a strongly distorted Watson-Crick G x C base-pair.

Our previous NMR and modeling studies have shown that the single-stranded 19mer oligonucleotides d(AGCTTATC-ATC-GATAA GCT) -ATC- and d(AGCTTATC-GAT-GATAAGCT) -GAT- encompassing the strongest topoisomerase II cleavage site in pBR322 DNA could form stable hairpin structures. A new sheared base-pair, the pyrimidine-purine C x A, was found to close the single base -ATC- loop, while -GAT- displayed a flexible loop of three/five residues with no stabilizing interactions. Now we report a structural study on -GAC-, an analog of -GAT-, derived through the substitution of the loop residue T by C. The results obtained from NMR, non-denaturing PAGE, UV-melting, circular dichroism experiments and restrained molecular dynamics indicate that -GAC- adopts a hairpin structure folded through a single residue loop. In the -GAC- hairpin the direction of the G9 sugar is reversed relative to the C8 sugar, thus pushing the backbone of the loop into the major groove. The G9 x C11 base-pair closing the loop is thus neither a sheared base-pair nor a regular Watson-Crick one. Although G9 and C11 are paired through hydrogen bonds of Watson-Crick type, the base-pair is not planar but rather adopts a wedge-shaped geometry with the two bases stacked on top of each other in the minor groove. The distortion decreases the sugar C1'-C1' distance between the paired G9 and C11, to 8 A versus 11 A in the standard B-DNA. The A10 residue at the center of the loop interacts with the G9 x C11 base-pair, and seems to contribute to the extra thermal stability displayed by -GAC- compared to -GAT-. Test calculations allowed us to identify the experimental NOEs critical for inducing the distorted G.C Watson-Crick base-pair. The preference of -GAC- for a hairpin structure rather than a duplex is confirmed by the diffusion constant values obtained from pulse-field gradient NMR experiments. All together, the results illustrate the high degree of plasticity of single-stranded DNAs which can accommodate a variety of turn-loops to fold up on themselves.

Base Pairing↗

A single indicator technique to estimate extravascular lung water.

An estimate of extravascular thermal volume (EVTV) calculated from a single thermal indicator (SI) sampled in the pulmonary artery and the femoral artery was compared with direct gravimetric measurements of extravascular lung water (EVLW) on 47 dogs and with simultaneous double indicator (DI) dilution measurements made on 62 dogs and 38 humans with heat as the diffusible indicator and green dye as the intravascular indicator. For the gravimetric measurements the relation was EVTV(SI) = 1.00 EVLW(grav) + 61 ml r = 0.91. When compared with double indicator dilution measurements, the results were EVTV(SI) = 1.10 EVTV(DI) + 17 ml r = 0.94 for dogs and EVTV(SI) = 0.89 EVTV(DI) + 66 ml r = 0.97 for humans. A total of 1880 measurements were made over a range of EVTV(DI) from 70 to 2150 ml. The single indicator measurements of EVTV agrees with the double indicator measurements of EVTV and with the direct gravimetric measurements of EVLW and can be performed with standard catheters and without the withdrawal of blood.

Animals↗

Surface permeability and degradation of dental composites resulting from oral temperature changes.

The surface changes in dental composites caused by thermal cycling and different temperatures were evaluated by use of silver nitrate to stain the surface layers. Rapid temperature change resulted in the formation of layers within the surface which may have resulted from microcracking. Slow rates of change increased the depth and rate of diffusion of silver nitrate. Determination of the temperature changes at the surface of a restoration in the mouth indicated that in vivo temperature change is more likely to increase the depth of diffusion of oral fluids than to cause microcracking of the surface.

Body Temperature↗

Sodium stearate adsorption onto titania pigment.

The interaction of sodium stearate with titania pigment particles from aqueous suspension has been investigated using thermal analysis and infrared spectroscopy combined with electrochemical studies. Thermogravimetric analysis (TGA) was used both to determine the adsorption isotherm and to investigate the interaction behavior. Monolayer coverage is determined to be 0.95 mg/m(2); however, unlike the case with organic solvents, multilayer adsorption occurs. Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, combined with TGA, revealed that the surface monolayer is chemically bound. DRIFT spectroscopic data also indicated that the stearate bridged across two aluminum atoms. Subsequent stearate layers were physisorbed to the stearate monolayer and were readily removed with acetone washing.

Journal Article↗

Drugs acting as plasticizers in polymeric systems: a quantitative treatment.

The objective of the present study was to investigate and quantify the effects of ibuprofen, chlorpheniramine maleate and metoprolol tartrate on the thermal, mechanical and diffusional properties of polyacrylate-based films. Thin drug-containing films were prepared from organic Eudragit RS solutions and physicochemically characterized with respect to their glass transition temperature, mechanical properties and drug release kinetics in phosphate buffer pH 7.4. The apparent diffusion coefficient of the drug within the polymeric systems was determined by fitting an adequate solution of Fick's second law of diffusion to the experimentally determined release profiles. Importantly, the glass transition temperature of the films significantly decreased with increasing initial drug content, whereas the film flexibility and drug release rate increased. This clearly indicates that the three drugs act as efficient plasticizers for Eudragit RS. Interestingly, the mathematical analysis revealed that drug release was primarily controlled by diffusion. An increase in the initial drug content resulted in increased drug diffusivities and, thus, accelerated (absolute and relative) drug release rates. Importantly, quantitative relationships could be established between the drug diffusivity and the initial drug content. Based on this knowledge, the effects of the films' composition and thickness on the resulting drug release kinetics (also from coated solid dosage forms) can be predicted in a quantitative way.

Chemistry, Pharmaceutical↗

Colorimetric diffusion-reflection imaging high-throughput analysis of organic or inorganic compounds.

A colorimetric diffusion-reflection imaging (CDRI) high-throughput analytical technology was developed for library analysis. In the investigation, quartz sands were employed as light diffusion-reflection media. Inorganic and organic compounds with characteristic absorption bands in visible light could be quantified by this method. In the current investigation, compounds such as CrCl3, KMnO4, methylene blue, and acrolein were employed as substrates, and the UV spectrometer and traditional GC (with thermal conductivity detector) were employed to check the reliability of our CDRI technology. The current technology is capable of analyzing more then 100 samples simultaneously. Relative errors below 10% were achieved.

Acrolein↗

Electrochemical impedance spectroscopic analysis of dye-sensitized solar cells.

Electrochemical impedance spectroscopy (EIS) has been performed to investigate electronic and ionic processes in dye-sensitized solar cells (DSC). A theoretical model has been elaborated, to interpret the frequency response of the device. The high-frequency feature is attributed to the charge transfer at the counter electrode while the response in the intermediate-frequency region is associated with the electron transport in the mesoscopic TiO2 film and the back reaction at the TiO2/electrolyte interface. The low-frequency region reflects the diffusion in the electrolyte. Using an appropriate equivalent circuit, the electron transport rate and electron lifetime in the mesoscopic film have been derived, which agree with the values derived from transient photocurrent and photovoltage measurements. The EIS measurements show that DSC performance variations under prolonged thermal aging result mainly from the decrease in the lifetime of the conduction band electron in the TiO2 film.

Journal Article↗

Pain and small-fiber neuropathy in patients with hypothyroidism.

OBJECTIVE: To investigate large- and small-fiber function in patients with hypothyroidism and pain. METHODS: The authors studied 38 women treated for hypothyroidism and with painful extremities and 38 healthy controls. All subjects underwent neurologic examination of the extremities, neurophysiologic testing of large myelinated nerves, and thresholds for warmth detection (WDT), cold detection (CDT), heat-pain detection (HPDT), and cold-pain detection (CPDT) in one upper and both lower limbs. RESULTS: Eighteen patients had ongoing or intermittent ongoing distal pain in their limbs. Of these, 8 reported evoked and 10 reported paroxysmal pain. Fifteen patients had only diffuse musculoskeletal pain. A total of 16 patients had "hyperphenomena" (brush-evoked allodynia, punctate hyperalgesia, or cold allodynia or a combination of these, in their feet or hands or both). Eight patients were classified as having large fiber neuropathy, whereas 20 had "hypophenomena" (elevated thermal thresholds in their feet or hands or both). Thermal thresholds at the feet (WDT, CDT, and HPDT) were elevated (p = 0.001, p = 0.007, and p = 0.003, respectively) in the whole group of patients compared with the controls as well as WDT (p = 0.001) and CDT (p = 0.001) being elevated at the thenar eminence. All patients with ongoing, evoked, or paroxysmal pain had either hyperphenomena or hypophenomena or a combination of the two. CONCLUSIONS: Some patients treated for hypothyroidism have symptoms and findings compatible with small-fiber neuropathy or "hyperphenomena" indicating central sensitization.

Adult↗

Migration Dynamics of Fish Schools in Heterothermal Environments.

A mechanistic theory is presented to illustrate the ecologically scaled behavior of highly organized fish schools, which is principally controlled by thermal structure of the habitat. Starting from the equation governing the schooling dynamics of fish, and incorporating the hypothesized memory mechanism of thermal history into the model of klinokinesis, a mathematical formalism is developed which relates the individual processes of perception of temperature-gradients to the thermoregulatory migration of schools. The migration dynamics of schools in heterothermal environments is formulated as the modified Fick's law of diffusion in the presence of external potential field, which gives the advection-telegraph equation in combination with the continuity equation. A behavioral basis for the environmental potential function is proposed, which has been postulated ad hoc as a driving force of drift velocity in modeling biological aggregation patterns. It is predicted that the distribution of schools self-organizes into a critical state.Copyright 1998 Academic Press

Journal Article↗

Percutaneous peripheral revascularisation with excimer laser: equipment, technique and results.

Laser angioplasty has been evaluated for coronary applications since the early 1980s. Early complications of dissection, perforation and thermal injury led to a loss of enthusiasm for this technique. Recent advances in catheter development, including optimally spaced laser fibres, athermic 308 nm wave-length catheters, and saline infusion techniques have produced larger laser channels, minimised thermal injury and significantly reduced vessel dissection. This improvement in equipment and technique has led to the growing use of lasers in the field of percutaneous treatment of peripheral vascular interventions. Convincing data supporting laser use in thrombus may lead to widespread use of laser in diffuse, thrombotic, long occlusions in the SFA (superficial femoral artery) and for infrapopliteal disease treatment in patients with non-healing ulcers. Little literature exists on the specific results of 308 nm Excimer laser catheter use for peripheral angioplasty. Significant research is still needed to prove the role of debulking in peripheral applications, but upcoming clinical trial data from the PELA (peripheral angioplasty vs. laser study in long SFA occlusions) and LACI (laser angioplasty in chronic ishaemia) may help to solve these questions in the near future. This article attempts to outline the technical issues of laser catheter use in percutaneous peripheral interventions, including access, sheath selection and wire techniques to cross even the most challenging obstructions in the peripheral circulation.

Angioplasty, Laser↗

Effects of temperature on the fluorescence intensity and anisotropy decays of staphylococcal nuclease and the less stable nuclease-conA-SG28 mutant.

Frequency-domain fluorescence spectroscopy was used to investigate the effects of temperature on the intensity and anisotropy decays of the single tryptophan residues of Staphylococcal nuclease A and its nuclease-conA-SG28 mutant. This mutant has the beta-turn forming hexapeptide, Ser-Gly-Asn-Gly-Ser-Pro, substituted for the pentapeptide Tyr-Lys-Gly-Gln-Pro at positions 27-31. The intensity decays were analyzed in terms of a sum of exponentials and with Lorentzian distributions of decay times. The anisotropy decays were analyzed in terms of a sum of exponentials. Both the intensity and anisotropy decay parameters strongly depend on temperature near the thermal transitions of the proteins. Significant differences in the temperature stability of Staphylococcal nuclease and the mutant exist; these proteins show characteristic thermal transition temperatures (Tm) of 51 and 30 degrees C, respectively, at pH 7. The temperature dependence of the intensity decay data are shown to be consistent with a two-state unfolding model. For both proteins, the longer rotational correlation time, due to overall rotational diffusion, decreases dramatically at the transition temperature, and the amplitude of the shorter correlation time increases, indicating increased segmental motions of the single tryptophan residue. The mutant protein appears to have a slightly larger overall rotational correlation time and to show slightly more segmental motion of its Trp than is the case for the wild-type protein.

Amino Acid Sequence↗

Evidence for the existence of an effective interfacial tension between miscible fluids: isobutyric acid-water and 1-butanol-water in a spinning-drop tensiometer.

We report definitive evidence for an effective interfacial tension between two types of miscible fluids using spinning-drop tensiometry (SDT). Isobutyric acid (IBA) and water have an upper critical solution temperature (UCST) of 26.3 degrees C. We created a drop of the IBA-rich phase in the water-rich phase below the UCST and then increased the temperature above it. Long after the fluids have reached thermal equilibrium, the drop persists. By plotting the inverse of the drop radius cubed (r(-)(3)) vs the rotation rate squared (omega(2)), we confirmed that an interfacial tension exists and estimated its value. The transition between the miscible fluids remained sharp instead of becoming more diffuse, and the drop volume decreased with time. We observed droplet breakup via the Rayleigh-Tomotika instability above the UCST when the rotation rate was decreased by 80%, again demonstrating the existence of an effective interfacial tension. When pure IBA was injected into water above the UCST, drops formed inside the main drop even as the main drop decreased in volume with time. We also studied 1-butanol in water below the solubility limit. Effective interfacial tension values measured over time were practically constant, while the interface between the two phases remains sharp as the volume of the drop declines. The effective interfacial tension was found to be insensitive to changes in temperature and always larger than the equilibrium interfacial tension. Although these results may not apply to all miscible fluids, they clearly show that an effective interfacial tension can exist and be measured by SDT for some systems.

1-Butanol↗

Effects of copper vapor laser radiation on the root canal wall of human teeth: a scanning electron microscope study.

OBJECTIVE: The aim of this study is to analyze the effects of copper vapor laser radiation on the radicular wall of human teeth. MATERIALS AND METHODS: Immediately after the crowns of 10 human uniradicular teeth were cut along the cement-enamel junction, a chemical-surgical preparation of the radicular canals was completed. Then the roots were longitudinally sectioned to allow for irradiation of the surfaces of the dentin walls of the root canals. The hemi-roots were separated into two groups: one (control) with five hemi-roots that were not irradiated, and another (experimental) with 15 hemi-roots divided into three subgroups that were submitted to the following exposure times: 0.02, 0.05, and 0.1 s. A opper vapor laser (510.6 nm) with a total average power of 6.5 W in green emission, frequency of 16.000 Hz, and pulse duration of 30 ns was used. RESULTS: The results obtained by scanning electron microscope analysis showed the appearance of a cavity in the region of laser beam impact, with melting, recrystallization, and cracking on the edges of the dentin of the cavity due to heat diffusion. CONCLUSIONS: We determined that the copper vapor laser produces significant morphologic changes in the radicular wall of human teeth when using the parameters in this study. However, further research should be done to establish parameters that are compatible with dental structure in order to eliminate thermal damages.

Copper↗

Fluctuations in dispersion rheology

On the basis of the mesoscopic fluctuations of excess density, an experimentally verified model is developed to describe the effective shear viscosity and modulus of complex dispersions as a function of concentration, frequency, and temperature. A stochastic differential equation is used in the derivation of the zero-shear viscosity that shows large viscosity enhancement over a broad range of concentrations. The scaling behavior of shear thinning is determined from an anomalous diffusion equation. We obtain the shear-thinning exponent 1>beta>1 / 2, which depends on the tenuous fractal structure of the complex systems. The divergence of the shear viscosity in the vicinity of a critical temperature is derived as a dynamic critical phenomenon due to thermal fluctuations, and the critical exponent relates directly to the shear-thinning exponent.

Journal Article↗