Photoprotective effects of bucillamine against UV-induced damage in an SKH-1 hairless mouse model

UVB exposure of skin results in various biologic responses either through direct or indirect damage to DNA and non-DNA cellular targets via the formation of free radicals, reactive oxygen species (ROS) and inflammation. Bucillamine [N-(2-mercapto-2-methylpropionyl)-l-cysteine] is a cysteine-derived compound that can replenish endogenous glutathione due to its two donatable thiol groups, and functions as an antioxidant. In this study, we investigated the effects of bucillamine on UVB-induced photodamage using the SKH-1 hairless mouse model. We have demonstrated that UVB exposure (two consecutive doses, 230 mJ cm(-2)) on the dorsal skin of SKH-1 mice induced inflammatory responses (edema, erythema, dermal infiltration of leukocytes, dilated blood vessels) and p53 activation as early as 6 h after the last UVB exposure. Bucillamine pretreatment (20 mg kg(-1) of body weight, administered subcutaneously) markedly attenuated UVB-mediated inflammatory responses and p53 activation. We have also demonstrated that the stabilization and upregulation of p53 by UVB correlated with phosphorylation of Ser-15 and Ser-20 residues of p53 protein and that bucillamine pretreatment attenuated this effect. We propose that bucillamine has potential to be effective as a photoprotective agent for the management of pathologic conditions elicited by UV exposure.     

Activity-stability parameterization of homogeneous green oxidation catalysts

Small-molecule synthetic homogeneous-oxidation catalysts are normally poorly protected from self-destruction under operating conditions. Achieving design control over both activity and half-life is important not only in advancing the utility of oxidation catalysts, but also in minimizing hazards associated with their use and disposal. Iron(III)-TAML (tetraamido-macrocyclic ligand) oxidant catalysts rapidly activate H(2)O(2) for numerous significant processes, exhibiting high and differing activity and varying half-lives depending upon the TAML design. A general approach is presented that allows for the simultaneous determination of the second-order rate constant for the oxidation of a targeted substrate by the active catalyst (k(II)) and the rate constant for the intramolecular self-inactivation of the active catalyst (k(i)). The approach is valid if the formation of the active catalyst from its resting state and the primary oxidizing agent, measured by the second-order rate constant k(I), is fast and the catalyst concentration is very low, such that bimolecular inactivation pathways can be neglected. If the oxidation process is monitored spectrophotometrically and is set up to be incomplete, the kinetic trace can be analyzed by using the equation ln(lnA(t))/A(infnity)=ln(k(II)/k(i)[Fe(III)](tot)-k(i)t, from which k(II) and k(i) can be determined. Here, A(t) and A(infinity) are absorbances at time t and at the end of reaction (t=infinity), respectively, and [Fe(III)](tot) is the total catalyst concentration. Several tools were applied to examine the validity of the approach by using a variety of different Fe(III)-TAML catalysts, H(2)O(2) and tBuOOH as oxidizing agents, and the dyes safranine O and orange II as target substrates. Learning how catalyst activities (k(II)) and catalyst half-lives (k(i)) can be controlled by ligand design is an important step in creating green catalysts that will not persist in the environment after they have achieved their purpose.     

Ratio vectors of fourth degree polynomials

Let p(x) be a polynomial of degree 4 with four distinct real roots r₁<r₂<r₃<r₄. Let x₁<x₂<x₃ be the critical points of p, and define the ratios , k=1,2,3. For notational convenience, let σ₁=u, σ₂=v, and σ₃=w. (u,v,w) is called the ratio vector of p. We prove necessary and sufficient conditions for (u,v,w) to be a ratio vector of a polynomial of degree 4 with all real roots. Most of the necessary conditions were proven in an earlier paper. The main results of this paper involve using the theory of Groebner bases to prove that those conditions are also sufficient.