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PubMed1981

Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes.

The influence of human serum albumin and sex hormone binding globulin (SHBG) on the enzymic conversion of androstenedione to testosterone in human erythrocytes was investigated in vitro. Total plasma and albumin delayed the conversion rate of androstenedione, while SHBG increased it markedly. The effect of SHBG was largely abolished by heating to 60 degrees C for 1 h and by saturating its binding sites by DHT. The effect of both proteins was found to be related to their concentration. It appears that the binding sites of albumin provide a mechanism for retarding androstenedione uptake by the erythrocytes and that the high binding affinity of SHBG for testosterone facilitates the diffusion of this steroid out of the cell and thus, displaces the chemical equilibrium within the cell.

Androstenedione↗
PubMedDate not supplied

[ATC and EphMRA classifications: evolution from 1996 to 2003 and comparative analysis].

In their daily practice, health practitioners use one or more pharmacotherapeutic classifications. This diversity of classifications impairs the exchange of drug information, while the use of international or European classifications facilitates this diffusion. The "Hospital National Center of Drugs Information" (CNHIM) has integrated ATC (Anatomical Therapeutic Chemical) and EphMRA (European Pharmaceutical Marketing Research Association) classifications into its "Thériaque" database and has given the ATC official status in France by publishing a French translation. The objective of this article was to analyse the evolution of these two classification systems between 1996 and 2003, and to compare their allocations (of codes) with those for the drugs present in Thériaque in January 2002. The ATC comprises 14 principal groups and five levels of hierarchy, while the EphMRA comprises 16 principal groups and three to four levels. In Thériaque, the ATC is linked to active substances and drugs, and the EphMRA to drugs. Data-processing requests have made it possible to make a comparative analysis. Each year, the two classification systems evolve in terms of addition, suppression, modification and subdivision. Two principal differences are evident in the allocations in Thériaque (class EphMRA K "Hospital solutions" versus class ATC B "Blood and blood forming organ"; class EphMRA T "Diagnostic agents" versus class ATC V "Various"). Classifications evolve in parallel or independently, and although they are closely related to one another, they retain their specificities in terms of structure and uses.

Drug Information Services↗
PubMed2003

Maltodextrin transport through lamb.

The trimeric protein LamB of E. coli K12 (maltoporin) specifically facilitates the diffusion of maltose and maltooligosaccharides through the outer membrane and acts as a non-specific porin for small hydrophilic molecules. LamB serves also as a specific cell surface receptor for phages, including phage lambda. Each monomer consists of an eighteen-stranded antiparallel beta-barrel with nine surface loops (L1 to L9). Three loops fold into the beta-barrel, with loop L3 constricting the channel about half way. Monomers bind sugars independently of each other. Structural studies of maltoporin in complex with maltodextrin showed that the binding site, located at the channel constriction, was composed of : i) a "greasy slide", a left-handed helical arrangement of aromatic residues extending along the channel providing a hydrophobic path to the glycosyl moieties; and ii) an "ionic track", found on both sides of the channel constriction zone, providing residues available for forming hydrogen bonds with the sugars. The participation of the surface loops that cover the entry of the pore to phage binding and to sugar binding and transport has also been thoroughly investigated. Genetic and biochemical analyses suggest that some of the surface loops participate directly in the orientation and entry of maltooligosaccharides into the channel and, thus, control access to the binding site.

Amino Acid Sequence↗
PubMedDate not supplied

Adrenocortical zonation and the adrenal renin-angiotensin system.

The origins of mammalian adrenocortical zonation and the factors that maintain it are poorly understood. We have examined the roles of the tissue renin-angiotensin system and other paracrine morphogens and growth factors, and of specific transcription factors in adrenocortical cellular proliferation and development. From the data obtained, we propose a hierarchy of potential tissue modeling agents. These include morphogens, such as angiotensin II derived from an intraadrenal origin, growth factors, for example insulin-like growth factor-I, which can be considered to be the paracrine amplifiers of the morphogenic signal and finally transcription factors, such as c-fos and c-jun, that directly stimulate mitosis and other events of differentiation. In particular, transcription of representative genes in all three categories is increased in the glomerulosa by a low sodium diet, correlated with its hypertrophy and increased aldosterone synthase. Corticotrophin treatment tends to eliminate these indices of zonal differentiation. The adrenal cortex can also set up electrochemical gradients in response to stimulation. We postulate that the electrochemical gradient informs adrenocortical cells of their position within the gland, and may also facilitate "directed diffusion" of other morphogenic paracrine factors to precise locations of action.

Adrenal Glands↗
PubMed1997

In vitro and in vivo evaluation of BO-2727 against imipenem- and/or meropenem-resistant Pseudomonas aeruginosa.

The in vitro and in vivo activity of BO-2727, a carbapenem antibiotic, against resistant clinical isolates of Pseudomonas aeruginosa was studied. The geometric mean MICs against three groups of clinical isolates resistant to imipenem, meropenem and both carbapenems were 4.28, 4.08 and 5.44 micrograms/ml, respectively. BO-2727 also inhibited multiply antibiotic resistant isolates and laboratory mutants including a nalB-type mutant, which showed resistance to antibiotics such as imipenem, meropenem, ceftazidime, and/or ciprofloxacin, at less than 1.56 micrograms/ml. Overall, BO-2727 was 4-fold more active than biapenem, meropenem, panipenem and imipenem with an MIC90 of less than 6.25 micrograms/ml. The presence of basic amino acids in minimal medium less affected the antipseudomonal activity to a minimal extent, suggesting that BO-2727 has diverse penetration routes through the outer membrane other than OprD channel, which facilitates the diffusion of basic amino acids and carbapenems. The in vitro activity of BO-2727 reflected well in its therapeutic efficacy in experimental systemic infection in mice. These results suggest a possibility for the development of antipseudomonal carbapenems having activity against imipenem- and/or meropenem-resistant P. aeruginosa as well as a broad spectrum encompassing Gram-positive and -negative bacteria.

Animals↗
PubMed1999

Enhancement of enzyme reaction of magnetically anisotropic polyacrylamide gel rods immobilized with ferromagnetic powder and beta-D-galactosidase in an alternating magnetic field.

An immobilized polyacrylamide gel containing beta-D-galactosidase and Sr-Ba-ferrite was magnetized in a static magnetic field. The gel rods (10 mm long, O 2 mm) exhibiting magnetic anisotropy could move at lower than 100 Hz but not at higher than 250 Hz in an alternating magnetic field of 200 Oe. In case of immovability of gel rods, the apparent enzymic activity increased 3 times higher under exposure of an alternating magnetic field of 500 Oe (570 Hz). It could be explained that the ferromagnetic powder inside the gel might vibrate under the influence of elasticity of gel in the alternating magnetic field of 100 or 500 Oe and 0.2-12 kHz. This might facilitate faster diffusion of the substance inside the gel and transportation of the substrate and the product through the surface of gel. Consequently, the enzyme reaction was apparently activated.

Acrylic Resins↗
PubMedDate not supplied

[Vascular endothelial growth factor. From basic research to clinical application].

There is increasing evidence to support the concept that growth and metastasis of solid tumors, including those of gastrointestinal tract, is facilitated by neoangiogenesis. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful known inducer of endothelial cell growth. Therefore, VEGF is likely to contribute to tumor growth by promoting angiogenesis and stroma formation both directly, through its neovascularization inducing activity, and indirectly, by increasing vascular permeability. In addition, VEGF facilitates tumor diffusion favouring metastatic spread of cancer cells. In view of these implications, it is important to understand the physiopathological role played by this factor. In this review the authors present the accumulating body of data on the biological and functional properties of VEGF, paying special reference to new evidence on its contribution in tumor immune escape, through a marked inhibition of differentiation and activity of the professional antigen presenting cells (APC), namely dendritic cells (DC). As the molecular and cellular events that underlie the functional role of VEGF in tumor angiogenesis and immune suppression become better defined, rational pharmacological and/or gene therapies can be derived in order to treat those neoplasms, such as pancreatic adenocarcinoma, not well amenable to chemo- and radiotherapy or immunotherapy.

Dendritic Cells↗
PubMed1999

Cannabimimetic fatty acid derivatives: the anandamide family and other endocannabinoids.

In agreement with the highly lipophilic nature of (-)-delta9-tetrahydrocannabinol, all the endogenous ligands of cannabinoid receptors identified so far are derivatives of long chain fatty acids. N- Arachidonoylethanolamine (anandamide) and some of its polyunsaturated congeners have been found in mammalian brain and shown to activate the CB1 and, with a lower efficacy, CB2 cannabinoid receptor subtypes. More recently, 2-arachidonoylglycerol (2-AG), a widespread intermediate in the metabolism of phosphoglycerides, diacylglycerols and triglycerides, was also found to activate the cannabinoid receptors. The capability of palmitoylethanolamide, an anti-inflammatory metabolite, to activate CB2-like receptors is still being debated. Here we review: 1) the metabolic pathways suggested so far to underlie the biosynthesis and inactivation of anandamide and 2-AG, and 2) the current knowledge of the chemical bases for the interactions of anandamide and 2-AG with proteins of the endogenous cannabinoid system characterized so far, i.e. the CB1 and CB2 receptor subtypes, the membrane anandamide carrier , which facilitates anandamide diffusion into cells, and the enzyme fatty acid amide hydrolase , which catalyzes anandamide and, to a certain extent, 2-AG hydrolysis in vivo.

Animals↗
PubMed1992

Carbonic anhydrase 3 (CA3), a mesodermal marker.

Carbonic anhydrase 3 (CA3) is an abundant muscle protein characteristic of adult type 1, slow-twitch, fibres. The protein plays an important role in facilitated CO2 diffusion and diverse processes involving H+ and HCO-3 transport. Nucleotide sequence comparisons have identified putative promoter and enhancer regions in the 5' flanking sequences of the CA3 gene. Functional assays show that 2.8kb of 5' flanking sequence efficiently promotes transcription of a reporter gene in a muscle specific manner. Removal of sequences 5' to -722bp leads to a major loss of activity and this result implies that the proximal promoter region which includes a GArG box and four potential MyoD1 binding sites is not adequate for maximal transcription. The longest CA3 promoter construct is also active in 10T1/2 cells, which are precursor mesodermal cells and do not normally express CA3. In situ hybridization to mRNA in developing mouse embryos reveals a pattern of expression in myotomes and pre-muscles masses of the limb buds which is consistent with the regulation of CA3 by myogenic determination factors. These studies also showed that CA3 expression is not confined to cells of the muscle lineage since it is expressed in primitive mesoderm prior to the onset of myogenesis. Later in embryogenesis CA3 defines a subset of mesodermal cell types which includes not only skeletal muscle but also notochord and adipocytes.

Animals↗
PubMed1992

Non-radioactive nucleic acid probes: labelling and detection procedures.

A comprehensive overview is given concerning the in situ hybridization techniques using non-radioactively labelled probes. Details are given on the preparation of the probes with different reporter molecules and on the corresponding revealing assays. The development of non-isotopic labelling methods for nucleic acid probes has facilitated the diffusion of the in situ hybridization techniques to the research as well as to the clinical pathology laboratory. Non-radioactive probes have several advantages over the radiolabelled ones, including cost, shelf-life, safety and, last but not least, resolution of the signal.

2-Acetylaminofluorene↗
PubMedDate not supplied

Web-based radiology: a future to be created.

The impact of Internet on Medicine and Surgery is certainly remarkable, however the influence it had on Diagnostic Imaging was even stronger. The standardization of digital images acquired by the different medical imaging equipment has further facilitated the diffusion, transmission and communication in radiology within hospitals as well as on WEB. Radiology departments are bound to become "filmless" and with the present "tablet PC" radiological images will be directly transferred to the patient's bed in the relative electronic patient report. For radiology, interactive education could be envisaged with a tutor who guides the student(s) through the network. The Internet is an inexhaustible source of radiologic educational and information material with a number of sites of clinical cases, tutorial and teaching files, journals and magisterial lectures on-line. In a near future, the Internet could be applied in the simulation of clinicoradiologic cases or in applications of artificial intelligence with expert systems to support the solution of most complex cases.

Analog-Digital Conversion↗
PubMed2004

[Best practices in Community Nutrition: challenges and commitments].

Community Nutrition is a science in continuous evolution that needs to be adapted to changing nutritional problems and to geographical, cultural and socieconomical diversity. Best practices in community nutrition is a concept that facilitates enhanced diffusion and application of knowledge through the analysis of properly designed, executed and evaluated experiences. The conclusions of the five presentations in the session organized by the Spanish Society of Community Nutrition at the XIII Latin American Conference on Nutrition are analyzed. Also, the major challenges and commitments are described: planning and forecasting, intersectorial collaboration, international cooperation, evaluation and monitoring, empowerment, training, fostering institutional support, community participation, leadership, sustainability, continuity, transparency and dissemination. The needs to further develop cooperation and sharing of experiences in the area of community nutrition between Latin America and Spain is highlighted.

Benchmarking↗
PubMedDate not supplied

[Erythrocyte membrane transports of monoamine precursor amino acids in schizophrenia].

We have determined the erythrocyte membrane uptake of the monoamine precursors L-tyrosine (L-TYR) and L-tryptophane (L-TRYP) in 72 patients with schizophrenia: 21 without neuroleptic treatment and not depressed, 15 with neuroleptic treatment and depressed, 33 without neuroleptic treatment, 27 depressed, compared to: 59 control subjects, and 54 depressed patients. We found that the ratio of L-TYR facilitated membrane diffusion to that of L-TRYP is: decreased when the patients are depressed, increased when they are untreated. When untreated patients receive neuroleptics and are depressed, the ratio tends to equal that of depressed patients'. The meaning of these anomalies is analysed, using our up-to-date knowledge of the erythrocytes's role in uptaking and dispatching the human body amino-acids, and of the role of these uptakes in regulating the functional monoamine balance. We postulate that in depressions, Parkinson's disease and schizophrenia, a change of membrane fluidity occurs, being decreased in depressions and Parkinsons's disease, and increased in schizophrenia.

Adult↗
PubMedDate not supplied

Carrier-mediated outward transport of noradrenaline from adrenergic varicosities.

Normally, the carrier of the neuronal noradrenaline uptake mechanism (uptake1) is involved nearly exclusively in the inward transport of substrates. However, an outward transport is induced by either of two mechanisms: a. by the decrease (or reversal) of the Na+ concentration gradient across the neuronal membrane or b. by the "facilitated exchange diffusion" due to the inward transport of substrates of this carrier. In rat vasa deferentia (preloaded with 3H-noradrenaline; vesicular uptake, MAO and COMT blocked) all substrates of the carrier induced an outward transport of 3H-noradrenaline, in strict correlation with their Km for uptake1. The inward transport of these substrates increases the availability of the carrier on the inside of the neuronal membrane. However, additional factors contribute to this release: inhibition of re-uptake and co-transport of Na+ and Cl-. When vesicular uptake and MAO are intact, the strict correlation between Km and releasing effect was not seen. This is attributable to the very low axoplasmic concentration of 3H-noradrenaline under these conditions (i.e. to lack of substrate for outward transport). However, if substrates of uptake1 are also substrates of vesicular uptake, they are able to "mobilize" vesicularly stored 3H-noradrenaline and, hence, to induce substantial outward transport. These "good" releasers are identical with the "indirectly acting sympathomimetic amines" (i.e. they are tyramine-like).

Animals↗
PubMed1989

Methotrexate loading of red cell carriers by osmotic stress and electric-pulse methods: ultrastructural observations.

Transmission and scanning electron microscopy (EM) of osmotically stressed and electrically pulsed human erythrocyte carriers indicated that the mode of uptake of methotrexate (MTX) varied depending on the method of carrier production. The preswell and electroporation loading methods, apparently by facilitating passive diffusion across the cell membrane, promoted incorporation of the MTX directly into the cytoplasm of the carriers, as evidenced by their variable electron densities. The preswell method produced carriers displaying leptocytic characteristics, whereas the electroporation method produced carriers exhibiting sphero- and stomatocytic transformation. Hypotonic dialysis-prepared carriers took up MTX primarily by endocytosis and secondarily by passive diffusion. Endocytotic activity was not induced by the MTX. Scanning EM revealed that most of the dialysis-prepared carriers exhibited prominent invaginations of the cell surface. Transmission EM of serial thin sections through these carriers revealed numerous fully internalized, membrane-bound vesicles. Endocytotic activity caused progressive loss of membrane and resulted in the sphero- and stomatocytic transformation of the carriers.

Dialysis↗
PubMed1989

Theory of oxygen transport to tissue.

This review focuses on the theory of oxygen transport to tissue and presents the state of the art in mathematical modeling of transport phenomena. Results obtained with the classic Krogh tissue-cylinder model and recent advances in mathematical modeling of hemoglobin-oxygen kinetics, the role of hemoglobin and myoglobin in facilitating oxygen diffusion, and the role of morphologic and hemodynamic heterogeneities in oxygen transport in the microcirculation are critically discussed. Mathematical models simulate different parts of the pathway of oxygen molecules from the red blood cell, through the plasma, the endothelial cell, other elements of the vascular wall, and the extra- and intracellular space. Special attention in the review is devoted to intracapillary transport, which has been the subject of intensive theoretical research in the last decade. Models of pre- and postcapillary oxygen transport are also discussed. Applications to specific organs and tissues are reviewed, including skeletal muscle, myocardium, brain, lungs, arterial wall, and skin. Unresolved problems and major gaps in our knowledge of the mechanisms of oxygen transport are identified.

Biological Transport↗