Eficacia frente al sangrado gingival de una pasta dental con o-cymen-5-ol / Effectiveness of a toothpaste with o-cymen-5-ol against gingival bleeding

INTRODUCCIÓN: La gingivitis, si no se trata, puede provocar una periodontitis irreversible. Uno de los compuestos destinados a combatirla es el o-cymen-5-ol. OBJETIVO: El objetivo principal de este estudio fue demostrar la respuesta clínica de un dentífrico con o-cymen-5-ol al 0,1% más zinc, aplicado durante 7 días consecutivos al menos 2 veces/día, en pacientes con un índice de sangrado del surco gingival ≥ 25%. Como objetivo secundario se evaluó la tolerancia del producto. MÉTODOS: Estudio prospectivo, aleatorizado, doble ciego y controlado, para evaluar la eficacia de una pasta dental o-cymen-5-ol frente a un dentífrico con triclosán al 0,3% más zinc. Tras la visita basal, los datos se evaluaron a las 38 h., 48 h., 4 días y 7 días. Se emplearon modelos lineales de efectos mixtos, que fueron ajustados a los datos del ensayo para evaluar la respuesta del producto a lo largo del tiempo Resultados: Se incluyó a un total de 49 pacientes. El porcentaje medio de sangrado basal en ambos grupos fue homogéneo. Respecto al inicio del tratamiento, ambos grupos experimentaron una reducción significativa del índice de sangrado a las 38 horas. Esta reducción continuó ampliándose significativamente hasta un 67,5% y un 71,8%, respectivamente, a los 7 días del inicio del tratamiento. CONCLUSIONES: La pasta dental con o-cy-men-5-ol al 0,1% más zinc mejora el índice de sangrado gingival de forma significativa, ya a las 38 horas de aplicación, en individuos con un índice basal ≥25%, de forma similar a una pasta dental con triclosán al 0,3% más zinc

INTRODUCTION: Gingivitis, if not treated, can cause irreversible periodontitis. One of the compounds used to fight it is o-cymen-5-ol. OBJECTIVE: The main objective of this study was to demonstrate the clinical response of a toothpaste with o-cymen-5-ol at 0.1% plus zinc, applied during 7 consecutive days at least twice a day, in patients with a bleeding rate of the gingival sulcus ≥ 25%. As a secondary objective, the tolerance of the product is evaluated. METHODS: A prospective, randomised, double blind and controlled study, to evaluate the effectiveness of a toothpaste with o-cymen-5-ol compared to a toothpaste with triclosan at 0.3% plus zinc. After the baseline visit, the data were evaluated at 38 h, 48 h, 4 days and 7 days. Linear models of mixed effects were used, which were adjusted to the trial data in order to evaluate the response of the product in a study over time. RESULTS: A total of 49 patients were included. The average baseline percentage in both groups was homogeneous. With respect to the start of the treatment, both groups experienced a significant reduction in the bleeding rate at 38 h. This continuous reduction increased significantly up to 67.5% and 71.8%, respectively, at 7 days from the start of the treatment. CONCLUSIONS: Toothpaste with o-cymen-5-ol at 0.1% plus zinc improves the gingival bleeding rate significantly, with just 38 hours of application, in individuals with a baseline rate ≥ 25%, similarly to toothpaste with triclosan at 0.3% plus zinc

Cooperativity between T cell receptor complexes revealed by conformational mutants of CD3epsilon.

The CD3epsilon subunit of the T cell receptor (TCR) complex undergoes a conformational change upon ligand binding that is thought to be important for the activation of T cells. To study this process, we built a molecular dynamics model of the transmission of the conformational change within the ectodomains of CD3. The model showed that the CD3 dimers underwent a stiffening effect that was funneled to the base of the CD3epsilon subunit. Mutation of two relevant amino acid residues blocked transmission of the conformational change and the differentiation and activation of T cells. Furthermore, this inhibition occurred even in the presence of excess endogenous CD3epsilon subunits. These results emphasize the importance of the conformational change in CD3epsilon for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes.

Expression of a modified form of CD4 results in the release of an anti-HIV factor derived from the Env sequence.

We have studied the inhibitory effect of a CD4 chimera (CD4epsilon15) on HIV replication. This chimera is retained in the endoplasmic reticulum and traps the HIV envelope precursor gp160, preventing its maturation. Retroviral expression of the chimera strongly inhibited HIV replication even when it is expressed by only a minority of the T cell population. This protective effect on bystander nontransduced cells is mediated by a soluble factor that we identified as a fragment of HIV gp120 envelope protein and accordingly, we named this factor Env-derived antiviral factor (EDAF). Biochemical and immunoreactivity data show that EDAF is comprised of the gp120 C3-C5 regions and indeed, a recombinant protein bearing this sequence reproduces the anti-HIV properties of EDAF. Surprisingly, three tryptic peptides derived from EDAF are homologous but not identical with the corresponding sequences of the HIV isolate used to generate EDAF. We propose that EDAF results from an alternative intracellular processing of the Env protein provoked by its association to CD4epsilon15 and the selection of the best fitted Env protein sequences contained within the HIV isolate. The presence of EDAF improves the therapeutic potential of the CD4epsilon15 gene and it opens new possibilities for antiviral treatment and vaccine development.

Human TCR that incorporate CD3zeta induce highly preferred pairing between TCRalpha and beta chains following gene transfer.

TCR gene therapy is adversely affected by newly formed TCRalphabeta heterodimers comprising exogenous and endogenous TCR chains that dilute expression of transgenic TCRalphabeta dimers and are potentially self-reactive. We have addressed TCR mispairing by using a modified two-chain TCR that encompasses total human CD3zeta with specificities for three different Ags. Transfer of either TCRalpha:CD3zeta or beta:CD3zeta genes alone does not result in surface expression, whereas transfer of both modified TCR chains results in high surface expression, binding of peptide-MHC complexes and Ag-specific T cell functions. Genetic introduction of TCRalphabeta:zeta does not compromise surface expression and functions of an endogenous TCRalphabeta. Flow cytometry fluorescence resonance energy transfer and biochemical analyses demonstrate that TCRalphabeta:CD3zeta is the first strategy that results in highly preferred pairing between CD3zeta-modified TCRalpha and beta chains as well as absence of TCR mispairing between TCR:CD3zeta and nonmodified TCR chains. Intracellular assembly and surface expression of TCR:CD3zeta chains is independent of endogenous CD3gamma, delta, and epsilon. Taken together, our data support the use of TCRalphabeta:CD3zeta to prevent TCR mispairing, which may provide an adequate strategy to enhance efficacy and safety of TCR gene transfer.