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PubMed1991

Effect of a diffusion layer on the nature of enamel demineralization.

The aim of the present study was to evaluate the significance of diffusion barriers in the development of artificial caries-like lesions. A 30-mm2 enamel surface area was covered with a layer of filter paper and exposed to a gently agitated 50 mM acetate buffer, pH 4.5, containing either 0.1 or 1.0 ppm fluoride for up to 48 h at 20 degrees C. Similar enamel surfaces, but unprotected by filter paper, served as controls. It was found that below the filter paper an approximately 60-microns-deep caries-like lesion was developed exhibiting a preserved surface layer, the mineral content of which depended on the fluoride concentration of the buffer. The lesions of the control teeth without a filter paper coverage were erosion-like surface lesions. In the filter paper calcium and phosphate released from the enamel combined with fluoride from the bulk solution had established a supersaturation with respect to fluorapatite while the undersaturation with respect to hydroxyapatite was maintained, which caused a caries lesion to develop. The lesions produced in noncovered enamel by bulk solution unsaturated with respect to both apatites were erosion-like. It was concluded that a diffusion barrier can significantly favor the establishment of supersaturation with respect to fluorapatite and thus facilitate the development of a subsurface caries-like lesion at the expense of the erosion.

Apatites↗
PubMed1981

Pulmonary diffusing capacity for CO independent of alveolar CO concentration.

Pulmonary diffusing capacity for CO (DCO) was measured in human subjects at various CO concentrations using a rebreathing procedure. Two stable CO isotopes, 12C18O and 13C18O, were used. These isotopes could be simultaneously and continuously recorded by a respiratory mass spectrometer. For 13C18O the initial concentration in the rebreathing bag was constant at 0.00016, whereas it was varied for 12C18O from 0 to 0.00224. DCO was calculated for both isotopes. In five normal subjects, both D12C18O and D13C18O were independent of the rebreathing CO concentration, with mean values of 31.0 and 30.2 ml . min-1 . Torr-1, respectively. These results, which are at variance with those of Mendoza et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 43: 880-884, 1977), are compatible with the assumption that diffusion is the sole mechanism of alveolocapillary CO transport; in particular, there is no evidence for facilitated transport.

Adult↗
PubMed2004

Modeling of drug release from polymeric delivery systems--a review.

Polymeric drug delivery platforms have been receiving increasing attention in the past decade. The pharmaceutical industry is evaluating modes of delivery for their prized therapeutics at every step of the design cycle. Not only can the drug delivery platform transport drug molecules effectively, it can also improve patient compliance, offer greater patient convenience, and extend product lifecycles as patents expire. A large number of successful drug delivery systems have been developed as a result of an almost arbitrary selection of constituents and configurations. However, the development of advanced drug delivery systems relies on a judicious and careful selection of components, configurations, and geometries, which can be facilitated through mathematical modeling of controlled release systems. Mathematical modeling aids in predicting the drug release rates and diffusion behavior from these systems by the solution of an appropriate model, thereby reducing the number of experiments needed. It also aids in understanding the physics of a particular drug transport phenomenon, thus facilitating the development of new pharmaceutical products. The objective of this article is to review the spectrum of mathematical models that have been developed to describe drug release from polymeric controlled release systems. The mathematical models presented in this article have been grouped under diffusion controlled systems, swelling controlled systems, and erosion controlled systems as proposed by Langer and Peppas. Simple empirical or semi-empirical models and complex mechanistic models that consider diffusion, swelling, and erosion processes simultaneously are presented.

Chemistry, Pharmaceutical↗
PubMed2006

Model storage, exchange and integration.

The field of Computational Systems Neurobiology is maturing quickly. If one wants it to fulfil its central role in the new Integrative Neurobiology, the reuse of quantitative models needs to be facilitated. The community has to develop standards and guidelines in order to maximise the diffusion of its scientific production, but also to render it more trustworthy. In the recent years, various projects tackled the problems of the syntax and semantics of quantitative models. More recently the international initiative BioModels.net launched three projects: (1) MIRIAM is a standard to curate and annotate models, in order to facilitate their reuse. (2) The Systems Biology Ontology is a set of controlled vocabularies aimed to be used in conjunction with models, in order to characterise their components. (3) BioModels Database is a resource that allows biologists to store, search and retrieve published mathematical models of biological interests. We expect that those resources, together with the use of formal languages such as SBML, will support the fruitful exchange and reuse of quantitative models.

Animals↗
PubMed2002

Photomechanical delivery of 100-nm microspheres through the stratum corneum: implications for transdermal drug delivery.

BACKGROUND AND OBJECTIVES: Photomechanical waves (PWs) render the stratum corneum permeable and allow molecules to diffuse into the epidermis. The aim of this study was to investigate the probe size that could be delivered through the stratum corneum and into the epidermis. STUDY DESIGN/MATERIALS AND METHODS: A single PW was applied onto the rat skin in vivo. Aqueous suspensions of fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal delivery. The presence of the microspheres in the epidermis was measured by a fiber-based spectrofluorimeter after the stratum corneum was removed by tape-stripping (TS). RESULTS: Exposure of the rat skin to a PW permeabilized the stratum corneum and allowed the fluorescent microspheres to diffuse into the epidermis. CONCLUSIONS: The experiments show that PWs can facilitate the delivery of very large molecules and probes into the epidermis.

Administration, Cutaneous↗
PubMed2002

A cellular automata model of ligand passage over a protein hydrodynamic landscape.

The subject of ligand passage to an active site on a protein is addressed. Current views on the mechanism and the possible role of surface water are discussed. A theory is presented in which the pattern of hydropathic states of protein surface amino acid side chains is invoked as the influence on the relative hydrophobic effects of nearby water. The theory describes a ligand passage through the hydrodynamic near-surface water which exhibits temporary organized cavities resembling the chreodes introduced by Waddington. The passage of the ligand to the active site is facilitated by this dynamic mechanism. Cellular automata models of preferential directional diffusion through these chreodes support the theory. The theory may be invoked to explain a number of ligand-active site observations and serves as an idea for further studies.

Animals↗
PubMed1981

Effect of chemical modifiers of amino acid residues on proton conduction by the H+-ATPase of mitochondria.

The effect of chemical modifiers of amino acid residues on the proton conductivity of H+-ATPase in "inside out" submitochondrial particles has been studied. Treatment of submitochondrial particles prepared in the presence of EDTA (ESMP) with the arginine modifiers, phenylglyoxal or butanedione, or the tyrosine modifier, tetranitromethane, caused inhibition of the ATPase activity. Phenylglyoxal and tetranitromethane also caused inhibition of the anaerobic release of respiratory delta micro H+ in ESMP as well as in particles deprived of F1 (USMP). Butanedione treatment caused, on the contrary, acceleration of anaerobic proton release in both particles. The inhibition of proton release caused by phenylglyoxal and tetranitromethane exhibition in USMP a sigmoidal titration curve. The same inhibitory pattern was observed with oligomycin and with N,N'-dicyclohexylcarbodiimide. In ESMP, relaxation of delta micro H+ exhibited two first-order phases, both an expression of the H+ conductivity of the ATPase complex. The rapid phase results from transient enhancement of H+ conduction caused by respiratory delta micro H+ itself. Oligomycin, N,N'-dicyclohexylcarbodiimide, and tetranitromethane inhibited both phases of H+ release, and butanedione accelerated both. Phenylglyoxal inhibited principally the slow phase of H+ conduction. In USMP, H+ release followed simple first-order kinetics. Oligomycin depressed H+ release, enhanced respiratory delta micro H+, and restored the biphasicity of H+ release. Phenylglyoxal and tetranitromethane inhibited H+ release in USMP without modifying its first-order kinetics. Butanedione treatment caused biphasicity of H+ release from USMP, introducing a very rapid phase of H+ release. Addition of soluble F1 to USMP also restored biphasicity of H+ release. A mechanism of proton conduction by Fo is discussed based on involvement of tyrosine or other hydroxyl residues, in series with the DCCD-reactive acid residue. There are apparently two functionally different species of arginine or other basic residues: those modified by phenylglyoxal, which facilitate H+ conduction, and those modified by butanedione, which retard H+ diffusion.

Adenosine Triphosphatases↗
PubMed1983

Tetanus toxin inhibits the evoked outflow of an inhibitory (GABA) and an excitatory (D-aspartate) amino acid from particulate brain cortex.

In order to elucidate the mode of action of tetanus toxin, particles from rat forebrain were preloaded with tritiated GABA or D-aspartate, pre-incubated with tetanus toxin and then depolarized with K+, either in a batch procedure or by superfusion. The toxin depresses, but does not abolish, the evoked outflow of both amino acids in either system. Omission of Ca2+ decreases the outflow in the batch procedure by about 40%. The remaining outflow of either amino acid is insensitive to tetanus toxin, whereas the Ca2+ dependent outflow is completely inhibited. Antitoxin neutralizes the toxin but does not reverse its in vitro effects, once manifest. The toxin effects increase with time and temperature of pre-incubation. Pretreatment of the particles with V. cholerae neuraminidase, which is known to convert the long-chain gangliosides quantitatively into GM1, does not decrease the sensitivity to tetanus toxin. Besides particles from rat brain, those from chicken, but not those from frog brain, are toxin-sensitive when tested for GABA outflow in the batch procedure. Frog brain does not yield the typical ganglioside pattern, and also does not measurably bind 125I-tetanus toxin. The homoexchange diffusion of GABA, but not of D-aspartate, is slightly facilitated by tetanus toxin. We confirmed that tetanus toxin slightly inhibits the uptake of GABA, whereas that of D-aspartate is not measurably influenced. The accumulation, driven by a Na+/K+ gradient, of GABA into membrane vesicles from rat cortex is not affected by tetanus toxin. The present data support the hypothesis that tetanus toxin influences a process involved in the outflow of many transmitters, both excitatory and inhibitory.

Animals↗
PubMed1992

A source inventory and budget for chlorinated dioxins and furans in the United Kingdom environment.

Polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs) are ubiquitous in the environment. This paper estimates the present UK environmental loading of PCDD/Fs in soils, vegetation, air, water and sediments. Greater than 95% of the estimated total PCDD/F loading of 5.7 t in the UK environment is present in surface soils. Annual emissions from known primary sources of PCDDs and PCDFs are estimated. The most important of these include: municipal waste incinerator stack emissions (10.9 kg sigma PCDD/F per annum); industrial (7.7 kg/year) and domestic (5.1 kg/year) combustion of coal; clinical waste incinerators (1.7 kg/year); volatilisation from chlorophenol-treated substrates (1.7 kg/year) and combustion of leaded petrol by motor vehicles (0.7 kg/year). These sources are generally easy to define and reasonably reliable national estimates can be obtained. More difficult to quantify are secondary releases from the large UK stock of pentachlorophenol (PCP) and PCP-treated products, which may represent quantitatively one of the most important sources of total PCDD/Fs to the environment. Estimates of homologue-specific emissions indicate that combustion processes represent a far more significant source of tetra and penta CDD/Fs than do chlorophenols, which in turn constitute a greater source of hepta- and octachlorinated congeners. Direct emission of PCDD/Fs into the atmosphere from combustion processes facilitates their atmospheric transport to remote locations. This, coupled with the diffuse nature of combustion processes, means that the effects of PCDD/F contamination originating from anthropogenic combustion are more widespread than those from the use and disposal of chlorophenols. Contamination from chlorophenols will be more localised, owing to the insignificance of direct atmospheric release pathways for this source. Although there is reasonable agreement between the estimated current annual flux and the present UK environmental loading of PCDDs and PCDFs, a large discrepancy exists between the sum of the annual contributions from primary sources and this annual flux. Whilst the existence of an as yet unidentified source or sources or gross underestimates of known sources cannot be excluded, it is proposed that much of this discrepancy may be accounted for by secondary releases from the use and disposal of chlorophenols and the long-range transport, continued remobilisation and subsequent redeposition of PCDDs and PCDFs already present in the environment. Despite limited evidence for a modest decline in levels of PCDDs and PCDFs in some environmental compartments over the last 20 years, the environmental persistence of these chemicals means that they will remain in the UK environment for the foreseeable future despite recent action to curb primary emissions.

Air Pollutants↗
PubMed2004

Encapsulation of Fe(III) and Cu(II) complexes in NaY zeolite.

The use of nonporphyrin complexes encapsulated in zeolites as catalysts for oxidation reactions has been improved in the past decades by the discovery of increasing numbers of nonheme monoxygenases. The zeolite lattice can change the oxidative chemistry of the metallocomplexes, resulting in a catalytic effect different from those observed in homogeneous reactions. We report the encapsulation of iron and copper metallocomplexes with the ligand (2-hydroxybenzyl)(2-methylpyridyl)amine, Hbpa, and iron complexes with the ligand N,N'-bis(2-hydroxybenzyl)-N,N'-bis(2-methylpyridyl) ethylenediamine, H(2)bbpen. The zeolite-encapsulated metallocomplexes were prepared by diffusion of the ligands through the pores of the zeolites, already exchanged with the respective metal. The syntheses were performed in methanol and toluene solutions. Elemental analysis of solids with the Hbpa ligand have indicated better complexation for synthesis in toluene, where 74% of the iron atoms were coordinated by the ligand, against 37% for the synthesis in methanol. For the immobilization with the H(2)bbpen ligand in toluene it was observed that 46% of the iron atoms are coordinated, showing that the diffusion of the small ligand Hbpa through the zeolite cage was facilitated. The EPR spectra of the solids show signals at g = 2.0, which was attributed to an Fe-Fe interaction from the noncoordinated atoms, and g = 4.3 attributed to iron (III) in a rhombic geometry.

Benzyl Compounds↗
PubMed1983

Optic nerve meningioma.

An obese white woman presented with a 10-month history of progressive loss of vision in the right eye associated with a moderate proptosis. Examination of the fundus revealed marked congestion of the retinal vasculature with dilation of both the arteries and the veins. Numerous blot hemorrhages were scattered throughout the retina. The retina was elevated and appeared to be displaced anteriorly by solid tissue, but B-scan ultrasonography demonstrated only a serous detachment of a thickened, markedly convoluted retina. A diagnosis of optic nerve meningioma was considered, but definitive treatment was deferred because of medical problems. One month later the patient returned with a blind, painful right eye associated with neovascular glaucoma. High resolution CT coronal sections of the orbit showed generalized thickening of the optic nerve. The blind eye was enucleated facilitating exposure of the optic nerve which was found to be diffusely thickened by meningioma. The orbital portion of the optic nerve was subsequently removed and meningioma was demonstrated along its entire length to the bony optic canal. A transfrontal craniotomy was later performed to rid the patient of residual tumor.

Adult↗
PubMed2006

The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.

Antigens, Neoplasm↗
PubMedDate not supplied

Magnetic resonance assessment of acute and chronic stroke.

This article describes the important role of magnetic resonance imaging (MRI) in noninvasively assessing human focal ischemic stroke. Conventional MRI, diffusion-weighted and/or perfusion-weighted imaging have been used to facilitate both the qualitative and quantitative evaluation of heterogeneity of ischemic brain tissue. Further, by combining 2 or more magnetic resonance parameters, tissue-signature models have been developed that may be used as surrogate markers of tissue histopathology to characterize ischemic tissue as salvageable, necrotic, or tissue in transition to necrosis. Magnetic resonance tissue-signature models and results are presented. Dynamic changes in the evolution of ischemic tissue to infarction are also discussed. Recovery from acute stroke was studied with blood oxygenation level-dependent functional MRI to investigate the neural mechanisms for recovery from aphasia after stroke.

Acute Disease↗
PubMed1987

A computer data base for information on cancer treatment.

The Physician Data Query (PDQ) system is a clinically oriented computer data base developed to make recent information on cancer treatment widely available to the medical community. It represents an effort by the National Cancer Institute to promote diffusion of information about the treatment of cancer throughout the country, facilitate access to clinical trials, and accelerate the practical application of advances in research. The computer system provides information about state-of-the-art cancer treatment, which is updated monthly by an editorial board. It also includes a file of active cancer-research protocols and a directory of physicians and organizations providing cancer care to which physicians can gain access by geographic location as well as other features. PDQ was designed for physicians who may not be familiar with computers, to permit them to search for and display information without learning a specialized search language. PDQ uses a computer mainframe, which allows a large amount of data to be stored and made available to physicians rapidly and accurately. Transmission of information about cancer over commercial telecommunication networks gives health professionals access to PDQ by means of a computer terminal and local telephone lines.

Directories as Topic↗
PubMed1972

Blood microcirculation in the lymph node during the primary immune response.

Microangiography performed after total blood replacement with contrast material provided complete visualization of the vascular structures of the lymph node. Starting of the 2nd day, there is capillary redistribution throughout the cortex of the lymph node. The previously rather avascular nodules dissolve, and the cortical lymphoid tissue becomes uniformly vascular. Beginning on the 2nd day and reaching its peak on the 5th day, there is a significant increase in diameter and density of the subcapsular and medullary cord capillaries. 15 days after the antigenic stimulus, the appearance of the microvasculature returns to normal. The postcapillary venules (the microvascular structures which follow the capillaries) are widely distributed throughout. Histologically, only a fraction of these venules have a high endothelial lining (HE venules). Therefore, it is suggested that among the postcapillary venules, those with high endothelial lining should be specifically denoted. Great individual variation in the number of HE venules was observed, and no correlation with the timing of the immune response could be established. Whether the microvascular changes described lead to cellular change or are mere expressions of it cannot definitely be stated. However, the significant hypervascularity along the intranodal lymph pathways and the diffuse, even redistribution of the capillaries and postcapillary structures could greatly facilitate the humoral and cellular exchange between the circulating blood, the circulating lymph, and the tissues of the lymph node.

Angiography↗
PubMed1994

Drugs designed to maintain the transparence of the ocular lens.

Research into the biological basis of lens transparency has demonstrated the implication of lens sugar stress in the diabetic cataract whereas senile cataract is the result of natural degeneration which is enhanced by various external factors such as cosmic and ionizing rays, or oxidative processes. Drugs have been developed which are aimed at being effective on lens pathological physiology and metabolism, concurrently. Such molecules: aldose reductase inhibitors (ARIs: sorbinil, AD-5467, CT-112 and imirestat), acetyl salicylic acid (ASA), salicylate (SA) and sodium monomethyl trisilanol orthohydroxybenzoate (SMB, a prodrug for salicylate) have undergone pharmacodynamic, pharmacokinetic and/or clinical studies which are presented here. ARIs have shown efficacy in slowing down and preventing the progression of experimental sugar cataracts; sorbinil can partially reverse the very early morphological signs of sugar cataract. Sorbinil and imirestat have also demonstrated anti-oxidant properties. ARIs administration (per os or by topical instillation) generally results in lens levels compatible with concentrations that are efficient on biochemical mechanisms of cataract formation. However, at the present time, clinical evaluations are in progress and as yet, there is no confirmation of their efficacy in man. ASA and SA can prevent various mechanisms of lens protein denaturation; they inhibit AR and prevent, in vitro, the formation of some pigments found in the aged cataractous lens. Extrapolation of the ASA ocular pharmacokinetics results in animal to man, suggest that ASA administration per os could result in efficacious levels in the lens. This is also sustained by the observation of a reduced frequency of cataracts in ASA treated diabetic rheumatoid arthritis patients. SMB pharmacokinetic studies have shown small but persistent levels of the active principle in the lens. They suggest that the capsule slows down SA diffusion into the lens and that, on the contrary, lens epithelium facilitates its penetration. Preliminary results of pharmacodynamic studies are given.

Aldehyde Reductase↗