The Irritant Effects of Pharmaceutically Applied Surfactants

Dermal or transdermal medication may lead to irritant contact dermatitis. However, little information is available on the irritant effect of surfactants which are applied in topical formulations. Our aim was to examine the irritant effect of the most frequent compounds in topical products. A murine model was applied. The following compounds were examined: sodium lauryl sulphate (SLS), polyethoxylated (40EO) hydrogenated castor oil and sucrose laurate. SLS led to severe erythema, increase in transepidermal water loss (TEWL) and induced necrosis and accumulation of neutrophylic granulocytes and lymphocytes. Exposure to sucrose laurate resulted in an elevation of TEWL, but histology did not reveal impairment of the skin structure. Application of polyethoxylated (40EO) hydrogenated castor oil was not accompanied by tissue damage. Special attention should be paid to the irritant effect of SLS. Polyethoxylated (40EO) hydrogenated castor oil seems to be a non-irritant agent and sucrose laurate is also a promising candidate for application in topical preparations.     

Cytoplasmic tail deletion of T cell receptor (TCR) beta-chain results in its surface expression as glycosylphosphatidylinositol-anchored polypeptide on mature T cells in the absence of TCR-alpha

Surface expression of the T cell antigen receptor (TCR) in mature T cells requires the association of a variable heterodimer (alpha.beta or gamma.delta) with six invariant CD3 polypeptides (gamma, delta, epsilon-epsilon, zeta-zeta, or zeta-eta). We described here that deletion of the cytoplasmic tail polypeptide sequence (Lys-Lys-Lys-Asn-Ser) of TCR beta-chain (beta CT) results in expression of the truncated beta-chain on the surface of a mature T cell hybridoma line, in the absence of TCR-alpha, as a glycophosphatidylinositol (GPI)-anchored monomeric polypeptide. The GPI-anchored TCR-beta CT is not associated with CD3-epsilon and is incapable of conventional signal transduction. Association with TCR-alpha prevents beta CT from GPI-linkage formation. The alpha beta CT heterodimer binds the CD3 polypeptides, and the resultant TCR alpha beta CT/CD3 complex is capable of signal transduction. Our data show that a signal sequence for GPI-linkage formation is present in TCR-beta, and this alternative membrane anchoring mechanism can be utilized by beta-chain polypeptide lacking the CT sequence. We conclude therefore that in the absence of TCR-alpha expression, the beta-chain CT sequence plays an essential function in hindering GPI-linkage formation, thereby preventing escape of incompletely assembled TCR beta-chain to the cell surface of mature T cells.     

Effect of cathodic arc plasma treatment on the properties of WC–Co based hard metals

In this study, ion bombardment in a cathodic arc physical vapor deposition system was applied on WC–Co hard metal surfaces aiming to benefit from the diffusion acceleration effect, and to investigate the role of this effect on the surface composition, morphology and corrosion resistance of the materials. Chromium ions obtained via cathodic arc evaporation were accelerated under low (− 150 V) and high (− 1000 V) bias voltages in order to apply coating–bombardment cycles to sample surfaces. Substrate temperatures were measured by an optical pyrometer during the processes. The treated samples were characterized by scanning electron microscopy (SEM) and X-ray diffractometry (XRD). Temperature measurements showed that the sample temperature could be controlled precisely by adjusting the bias voltage. Temperatures in the range of 750–1200 °C were measured during the treatment depending on the duration of the high bias voltage cycles. XRD analysis showed η phase formation in the near surface regions of all treated samples. The amount of the formed η phase was shown to be dependent on the heating–cooling regime that varied with the applied mode of bias. The corrosion behavior of the samples was investigated by immersing treated and untreated samples in a solution of 5% H₃PO₄ containing 1 g/l Zn^{+ 2} for 24 h at 50 °C. The samples were investigated via SEM observations after immersion. Cathodic arc plasma treated samples showed a better resistance to corrosion in this environment.     

Increased sialylation of polymeric immunoglobulin A1: mechanism of selective glomerular deposition in immunoglobulin A nephropathy?

Monoclonal antibodies which recognize antigenic determinants expressed by T-cells and Ig-bearing cells, respectively, allowed lymphocyte subpopulations involved in allograft rejection of muscle transplants to be identified in the teleost fish Dicentrarchus labrax (L.). The monoclonal antibody DLT15 first allowed recognizing T-cells involved in an in vivo antigen-driven cellular response in teleosts. Immunohistochemical studies showed a high density of lymphocytes in allografts and provided evidence of predominance of T-cells. The heterogeneity of the cell populations recognized by the antibodies was evidenced by the different size, cytology, and staining patterns of T-cells and Ig-bearing cells.     

A new tool for studying the molecular architecture of the fungal cell wall: one-step purification of recombinant trichoderma beta-(1-6)-glucanase expressed in Pichia pastoris

We assessed the anesthetic properties of helium and neon at hyperbaric pressures by testing their capacity to decrease anesthetic requirement for desflurane using electrical stimulation of the tail as the anesthetic endpoint (i.e., the minimum alveolar anesthetic concentration [MAC]) in rats. Partial pressures of helium or neon near those predicted to produce anesthesia by the Meyer-Overton hypothesis (approximately 80-90 atm), tended to increase desflurane MAC, and these partial pressures of helium and neon produced convulsions when administered alone. In contrast, the noble gases argon, krypton, and xenon were anesthetic with mean MAC values of (+/- SD) of 27.0 +/- 2.6, 7.31 +/- 0.54, and 1.61 +/- 0.17 atm, respectively. Because the lethal partial pressures of nitrogen and sulfur hexafluoride overlapped their anesthetic partial pressures, MAC values were determined for these gases by additivity studies with desflurane. Nitrogen and sulfur hexafluoride MAC values were estimated to be 110 and 14.6 atm, respectively. Of the gases with anesthetic properties, nitrogen deviated the most from the Meyer-Overton hypothesis. Implications: It has been thought that the high pressures of helium and neon that might be needed to produce anesthesia antagonize their anesthetic properties (pressure reversal of anesthesia). We propose an alternative explanation: like other compounds with a low affinity to water, helium and neon are intrinsically without anesthetic effect.     

Biochemical and genetic characterization of a gentisate 1, 2-dioxygenase from Sphingomonas sp. strain RW5

A 4,103-bp long DNA fragment containing the structural gene of a gentisate 1,2-dioxygenase (EC 1.13.11.4), gtdA, from Sphingomonas sp. strain RW5 was cloned and sequenced. The gtdA gene encodes a 350-amino-acid polypeptide with a predicted size of 38.85 kDa. Comparison of the gtdA gene product with protein sequences in databases, including those of intradiol or extradiol ring-cleaving dioxygenases, revealed no significant homology except for a low similarity (27%) to the 1-hydroxy-2-naphthoate dioxygenase (phdI) of the phenanthrene degradation in Nocardioides sp. strain KP7 (T. Iwabuchi and S. Harayama, J. Bacteriol. 179:6488-6494, 1997). This gentisate 1,2-dioxygenase is thus a member of a new class of ring-cleaving dioxygenases. The gene was subcloned and hyperexpressed in E. coli. The resulting product was purified to homogeneity and partially characterized. Under denaturing conditions, the polypeptide exhibited an approximate size of 38.5 kDa and migrated on gel filtration as a species with a molecular mass of 177 kDa. The enzyme thus appears to be a homotetrameric protein. The purified enzyme stoichiometrically converted gentisate to maleylpyruvate, which was identified by gas chromatography-mass spectrometry analysis as its methyl ester. Values of affinity constants (Km) and specificity constants (Kcat/Km) of the enzyme were determined to be 15 microM and 511 s-1 M-1 x 10(4) for gentisate and 754 microM and 20 s-1 M-1 x 10(4) for 3, 6-dichlorogentisate. Three further open reading frames (ORFs) were found downstream of gtdA. The deduced amino acid sequence of ORF 2 showed homology to several isomerases and carboxylases, and those of ORFs 3 and 4 exhibited significant homology to enzymes of the glutathione isomerase superfamily and glutathione reductase superfamily, respectively.     

Conjugated linoleic acid decreases hepatic stearoyl-CoA desaturase mRNA expression

Conjugated dienoic derivatives of linoleic acid (CLA) is a collective term for positional and geometric isomers of linoleic acid that occur naturally in foods. The two predominant isomers of CLA are the c9,t11 and t10,c12. One of the effects of CLA is to modify membrane fatty acid composition by decreasing the activity of stearoyl-CoA desaturase enzyme activity. We analyzed the changes of stearoyl-CoA desaturase gene 1 (scd1) mRNA to further define the mechanism for the decrease in Scd enzyme activity by CLA. Mice fed for two weeks with either a fat-free high carbohydrate diet (CHO) or a 5.0% corn oil diet (CO), supplemented with 0.5% CLA had a 45% and 75% decrease respectively, in scd1 mRNA levels in the liver. Consistent with the effects observed in mice, 150 microM CLA suppressed the expression of scd1 mRNA in the H2.35 mouse liver cells by 60%. Further studies with enzymatically prepared c9,t11 isomer showed that the inhibitory effect of CLA on scd1 mRNA expression in H2.35 liver cells was by isomers other than the c9,t11-CLA.     

The Liar, Context and Logical Form

This essay attempts to give substance to the claim that the liar'sparadox shows the truth predicate to be context sensitive. The aim ismodest: to provide an account of the truth predicate's contextsensitivity (1) that derives from a more general understanding ofcontext sensitivity, (2) that does not depend upon a hierarchy ofpredicates and (3) that is able to address the liar's paradox. Theconsequences of achieving this goal are not modest, though. Perhapssurprisingly, for reasons that will be discussed in the last section ofthis essay, a natural account of the truth predicate's contextsensitivity appears to lead naturally to a version of the correspondencetheory of truth according to which the truth predicate can be understoodas a relation holding between a sentence and a salient set of contexts.The plan of this essay is as follows. Section 1 contains a generalaccount of context sensitivity. The purpose of this section is toisolate certain features of context sensitivity and formal methods oftreating them, which we will then apply to the truth predicate. Section 2then outlines two minimal conditions to be satisfied by a truthpredicate. In Section 3, I present a version of the liar paradoxthat results from these conditions and the assumption that the truthpredicate is not context sensitive in the sense described in sectionone. Finally, in section four, I provide what appear to be naturalconsequences of a truth predicate's context sensitivity. Section 4 isadmittedly speculative and points in the direction for future research.