The osteogenic growth peptide (OGP) was characterized recently in regenerating bone marrow (BM) and normal serum. In vitro, the OGP regulates stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablation BM regeneration. The present results in normal mice show that OGP induces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogeneic BM transplants, OGP stimulates hematopoietic reconstruction and doubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semiallogeneic graft recipients suggest no preferential effect of OGP on residual host cells. The data implicate OGP in the acceleration of hematopoiesis secondary to expansion of the stromal microenvironment and/or enhancement of stroma-derived signals to stem cells. The low-dose effectiveness of OGP is explained by the demonstration of an autocrine positive feedback loop that together with the OGP-binding protein sustains high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP-induced balanced multi-lineage enhancement of hematopoiesis and possible replacement of expensive recombinant cytokines by a readily synthesized peptide.
An alternative method for external coaptation of fractures in young animals utilizes tongue depressors incorporated in a bandage consisting of a thick layer of cotton padding, gauze bandaging, and adhesive tape. This method was used in 13 cases with fractures of the tibia or the radius and ulna, some of which were open, Five cases (four dogs and a cat) had displaced fractures, and eight cases had either nondisplaced or only mildly displaced fractures. Size of the animal was not considered a limiting factor Bandages were examined periodically, All fractures healed uneventfully and the splints were removed 21-to-44 days after application, This method of external coaptation proved to be easy to apply and modify during the healing process and was applicable to a wide variety of fractures with good results.
A novel approach to the assessment of the toxicity of the chlorinated pesticide hexachlorocyclohexane (lindane) and the organic solvents methanol and w-butanol, employing endothelial cells in culture, is presented. This highly reproducible system involves the simultaneous treatment of [51Cr]. and [3H]arachidonic acid-labeled rat pulmonary endothelial cells with xenobiotics combined with glucose oxidase-generated H2O2, phospholipase c, streptolysin S, diethyldithiocarbamate (DDC), sodium nitroprusside (NP), histone, and trypsin. Such treatment leads to synergistic cell killing and the release of arachidonic acid (Ginsburg and Kohen, 1995b). Thus, subtoxic amounts of xenobiotics that failed to kill the cells became highly cytolytic when combined with the various mixtures of agonists. Cytotoxicity and the release of membrane lipids are strongly inhibited by catalase, by Mn2+, and by soybean trypsin inhibitor. The "synergism" concept of cellular toxicity is relevant, in particular, in infectious and inflammatory sites where phagocyte- and tissue-derived proinflammatory agonists are generated in large amounts as a result of cellular damage induced either by pathogenic microorganisms, by activated phagocytes, or by xenobiotics. This simple and inexpensive in vitro model of cellular cytotoxicity might supplement and even replace the more costly animal experimentations involved in the assessment of the toxicity and safety of newly designed drugs.
This work describes the synthesis and characterization of a new family of antioxidants. The molecules have the same active group, but different oil-to-water and octanol-to-water partition coefficients due to different substituents. Three new molecules were synthesized based on the chemical structure of the primary amide attached to a thiophosphate group forming an amidothionophosphate. The amidothionophosphate molecules were exposed to the oxidative stress of hydrogen peroxide and sodium hypochlorite, and the chemical changes following the exposure were monitored by 31P NMR. The reaction constants with the reactive oxygen species hydroxyl radical and superoxide radical were also calculated and found to be 1.5 x 10(9) M-1s-1 and 8.1 x 10(2) M-1s-1, respectively. To elucidate the ability of amidothionophosphates to act as antioxidants in protecting lipids and proteins, we examined damage prevention in bovine serum albumin, egg phosphatidylcholine liposomes, and lipid emulsions following oxidative stress. Amidothionophosphate showed unique protection properties in these models. In contrast to other antioxidant molecules (ascorbic acid, cysteine, and alpha-tocopherol) the new group did not have any pro-oxidative effects as measured by oxygen consumption from buffer solutions containing amidothionophosphates and cupric sulfate as a source of redox-active metal ions. Amidothionophosphates reduced significantly and in a dose-dependent manner the oxidative burst in human neutrophils as measured by luminol-dependent chemiluminescence, and they also markedly depressed the killing of human fibroblasts by mixtures of glucose oxidase and streptolysin S. The toxicity of these molecules was tested by IP injection of doses up to 1000 mg/kg to white Sabra mice. No mortality was observed 30 d after administration of up to 500 mg/kg.
We describe a new approach for constructing large-scale artificial neural networks. The novelty of our approach is based on the concept of electroholography (EH), which permits interconnecting of electronic neurons by minute-volume holograms, using the voltage-controlled photorefractive effect in paraelectric crystals. Crystals of potassium lithium tantalate niobate (KLTN) in the paraelectric phase are shown to be suitable for implementing this concept. A small network composed of two KLTN crystals on which holographic connections are recorded is presented to demonstrate the EH approach.
Phospholipase A2 (PLA2) and H2O2, secreted from activated inflammatory cells, play a central role in the tissue damage occurring in inflammatory processes. However, while exogenous PLA2 alone does not cause cell lysis, it readily does so when acting with H2O2. We have found that H2O2 degrades cell surface proteoglycans, thus rendering the membrane PL accessible to hydrolysis by exogenous PLA2. This novel mechanism introduces a role for cell surface proteoglycans in protection of cells from damage by pro-inflammatory agents, and may assign a central role for the combined action of H2O2 and PLA2 in inflammatory and bacteriocidal processes.
The representation of a quantum system by an evenly spaced Fourier grid is examined. This grid faithfully represents wave functions whose projection is contained in a rectangular phase space. This is mathematically equivalent to a band limited function with finite support. In general, have packets decay exponentially in classically forbidden regions of phase space. This idea is then used first to optimize the rectangular shape of the Fourier grid, leading to exponential convergence. Nevertheless, in most cases the representation is suboptimal. The representation efficiency can then be extremely enhanced by mapping the coordinates. The mapping procedure reshapes the wave function to fit into the rectangular Fourier shape such that the wasted phase space area is minimal. It is shown that canonical transformations, which rescale the coordinates, improve the representation dramatically. A specific scaling transformation enables the representation of the notoriously difficult Coulomb potentials. The scaling transformation enables one to extract almost as many converged eigenstate energies as there are grid points. The method is extendible to more than one dimension, which is demonstrated by the study of the H + 2 problem. This scaling transformation can bridge the gap between quantum chemistry and quantum molecular dynamics by enabling the treatment of electronic problems in the vicinity of Coulomb potentials by grid methods developed for molecular dynamics.
Background/airns: Carbobenzoxy-phenylalanyl-methionine (CBZ-Phe-Met), a known inhibitor of the chemotactic peptide N- formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro, has not been evaluated as a topical anti-inflammatory agent in vivo. In order to measure the effect of CBZ-phe-met, one needs a repeat- able, quantitative, easily obtainable standard measurement of the edema formation. In this study, a caliper designed for measuring soft materials was used to evaluate the edema, in- duced by croton oil on rabbit ears, as well as the effects of CBZ- phe-met. Methods: The model used in this study was croton-induced in- flammation on rabbit ears. A caliper for measuring soft materials ( European standard DIN 863 part 3, manufactured by TESA Ltd., Renens, Switzerland) was used to evaluate the edema, which is part of the inflammatory effect . The action of CBZ-phe- met and two other anti-inflammatory agents; hydrocortisone and Na-ibuprofen, were compared.
Results: CBZ-phe-met 1-5% was found to reduce the edema on rabbit ears induced by croton oil by 15 to 93%. 5% CBZ-phe- met was found to be as effective as 5% Na-ibuprofen and 0.1% hydrocortisone. Conclusion: The caliper for soft materials was found to be suit- able for measuring the edema induced by croton-oil, as well as the reducing edema due to anti-inflammatory treatment. It was also found that CBZ-phe-met is a potent topical anti-inflamma- tory agent in the croton-oil-induced inflammatory model. This may indicate a new approach in the treatment of inflammation. Key words: Soft material caliper - inflammation - N-formyl-me- thionyl-leucyl-phenylalanine (fMLP) - carbobenzoxy-phenylala- nyl-methionyl (CBZ-phe-met).
An attempt was made to incorporate alpha-tocopherol in negatively and positively-charged submicron emulsions, with the aim of providing an effective topical preparation against skin oxidative damage. In cell culture toxicity experiments using human fibroblast it was shown that the positively-charged alpha-tocopherol emulsion did not exhibit any toxic effect despite the low dilution and respective high concentration used. Negatively and positively-charged submicron emulsions of alpha-tocopherol and their respective blank emulsions were topically applied to rats that were subjected to UVA irradiation under different experimental conditions. No difference was observed between the negatively and positively-charged alpha-tocopherol submicron emulsions regarding the rate of oxidation and peroxyl radical scavenging ability of skin homogenates and both were able to protect rat skin against oxidative stress. However, in a non-invasive evaluation of the lipid hydroperoxidation process in rat skin following exposure to UVA irradiation, the positively-charged alpha-tocopherol submicron emulsion elicited a significantly better protective effect than the corresponding negatively-charged emulsion. These results suggest that the positively-charged emulsion exhibits a more prolonged residence time in the uppermost layers of the skin than the negatively-charged emulsion.
The invention provides a process for the prepn. of long-chain alkyl glycosides, comprising reacting a glucose-contg. reactant and a C8-C18 fatty alc. in the presence of a glucosidase and a reaction promoter effective to promote the formation of the alkyl glycoside when the promoter is present in an amt. of <∼50% of the total reaction mixt. [on SciFinder(R)]
The invention relates to a compound of formula (I) in which X1 and X2 each independently represents an oxygen or nitrogen atom; p, m and n are each independently an integer of at least 2; R, R1 and R2 each independently represents a hydrogen atom; a halogen atom; an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; a group R3O in which R3 is hydrogen atom, an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; optionally substituted acyl or optionally substituted aryl or heteroaryl; a group R4O(O)C in which R4 is a hydrogen atom or an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; a group -SR5 in which R5 is a hydrogen atom or an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; a group -NR6R7 in which R6 and R7 each independently represents a hydrogen atom, an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; optionally substituted acyl; or an optionally substituted phosphate ester group. The invention also relates to processes for the preparation of compounds of the formula and to pharmaceutical compositions containing the same.
The relative decline in party membership in West-European countries over the last three decades is an accepted fact in the comparative literature on party organization. However, the bare facts do not explain the reasons for such decline and may leave the feeling that the process is irreversible. A number of scholars relate party membership decline to the introduction of public finance of political parties. They suggest that public financing laws and related arrangements have a negative effect on efforts to mobilize party membership, leading to a decline in political participation. In this article, drawing mainly on the Israeli experience, I argue that public funding does not necessarily lead to membership decline, but that changes in the internal competition rules for electing party candidates to national or local posts may affect party membership more than any other variable. Thus, the decline in membership that has been considered to be irreversible, is in fact highly reversible. [ABSTRACT FROM AUTHOR]Copyright of European Journal of Political Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
The relative decline in party membership in West-European countries over the last three decades is an accepted fact in the comparative literature on party organization. However, the bare facts do not explain the reasons for such decline and may leave the feeling that the process is irreversible. A number of scholars relate party membership decline to the introduction of public finance of political parties. They suggest that public financing laws and related arrangements have a negative effect on efforts to mobilize party membership, leading to a decline in political participation. In this article, drawing mainly on the Israeli experience, I argue that public funding does not necessarily lead to membership decline, but that changes in the internal competition rules for electing party candidates to national or local posts may affect party membership more than any other variable. Thus, the decline in membership that has been considered to be irreversible, is in fact highly reversible. [ABSTRACT FROM AUTHOR]Copyright of European Journal of Political Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
