Effect of Whitening Toothpastes with Different Active Agents on the Abrasive Wear of Dentin Following Tooth Brushing Simulation.

The aim of this research was to evaluate the abrasive dentin wear that can be induced by three commercial whitening toothpastes following a tooth-brushing simulation (TBS) corresponding to a three-month period. Sixty human canines were selected, and the roots were separated from the crowns. Then the roots were randomly divided into six groups (n = 10) and were submitted to TBS using the following slurries: Group 1-deionized water (RDA = 5); Group 2-ISO dentifrice slurry (RDA = 100); Group 3-a regular toothpaste (RDA = 70); Group 4-a charcoal-containing whitening toothpaste; Group 5-a whitening toothpaste containing blue covasorb and hydrated silica; and Group 6-a whitening toothpaste containing microsilica. Following TBS, surface loss and surface roughness changes were evaluated using confocal microscopy. Additionally, surface morphology and mineral content changes were observed using scanning electron microscopy and energy-dispersive X-ray spectroscopy. The deionized water group presented the lowest surface loss (p < 0.05), while the charcoal-containing toothpaste presented the highest surface loss, followed by ISO dentifrice slurry (p < 0.001). Blue-covasorb-containing and regular toothpastes did not present statistically significant differences (p = 0.245), and neither didmicrosilica-containing toothpaste or ISO dentifrice slurry (p = 0.112). The surface height parameters and surface morphology changes of the experimental groups followed the surface loss patterns, while no differences were detected in mineral content after TBS.Although the charcoal-containing toothpaste exhibited the highest abrasive wear to dentin, according to ISO 11609, all the tested toothpastes exhibited appropriate abrasive behavior towards dentin.

Disappearance of Temporal Collinearity in Vertebrates and Its Eventual Reappearance.

It was observed that a cluster of ordered genes (Hox1, Hox2, Hox3…) in the genome are activated in the ontogenetic units (1, 2, 3 …) of an embryo along the Anterior/Posterior axis following the same order of the Hox genes. This Spatial Collinearity (SC) is very strange since it correlates events of very different spatial dimensions. It was later observed in vertebrates, that, in the above ordering, first is Hox1expressed in ontogenetic unit 1, followed later by Hox2 in unit 2 and even later Hox3 in unit 3. This temporal collinearity (TC) is an enigma and even to-day is explored in depth. In 1999 T. Kondo and D. Duboule, after posterior upstream extended DNA excisions, concluded that the Hox cluster behaves 'as if' TC disappears. Here the consideration of TC really disappearing is taken face value and its repercussions are analyzed. Furthermore, an experiment is proposed to test TC disappearance. An outcome of this experiment could be the reappearance (partial or total) of TC.

Physical Laws Shape Up HOX Gene Collinearity.

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC), where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3' to 5' direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior-Posterior axis of the embryo. Expression of Hox1 occurs in E1, Hox2 in E2, Hox3 in E3, etc. Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC, first Hox1 is expressed in E1; later, Hox2 is expressed in E2, followed by Hox3 in E3, etc. Lately, doubt has been raised about whether TC really exists. A biophysical model (BM) was formulated and tested during the last 20 years. According to BM, physical forces are created which pull the Hox genes one after the other, driving them to a transcription factory domain where they are transcribed. The existing experimental data support this BM description. Symmetry is a physical-mathematical property of matter that was explored in depth by Noether who formulated a ground-breaking theory (NT) that applies to all sizes of matter. NT may be applied to biology in order to explain the origin of HGC in animals developing not only along the A/P axis, but also to animals with circular symmetry.

Development and validation of LC-MS/MS method for the determination of UV-filters across human skin in vitro.

A novel High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of the in vitro skin permeation profile of four UV filters. The sunscreen products contained the following components: octocrylene (OC), ethylhexyl methoxycinnamate (EHMC), diethylamino hydroxybenzoyl hexyl benzonate (DHHB) and ethylhexyl salicylate (EHS). The target compounds were analyzed by HPLC-MS/MS method in positive ionization electrospray (ESI) in Multiple Reaction Monitoring (MRM) mode. The proposed method was validated in terms of the detection (LOD) and quantification limits (LOQ), linearity range, intra- and inter- day precision and accuracy of the analysis. The stability of the target compounds in solutions was also studied. All tests provided satisfactory results illustrating acceptable method performance. Samples were analyzed with simple pretreatment procedure, necessary to achieve solvent change and preconcentration. To evaluate matrix effect, the slopes of the standard regression curves with those of the matrix-matched calibration curves were compared using the Student's t-test. Quantitative evaluation of the test samples was performed using external methanolic calibration curves. Accuracy was found within the range 94.37-108.76%. The method was successfully applied to the analysis of UV filters in samples after permeability studies, in Franz's cells, for 24 h, using human skin. Concentration of sunscreens in the acceptor phase at the timescale of 24 h was very low implying the safety of the products.

Effect of novel charcoal-containing whitening toothpaste and mouthwash on color change and surface morphology of enamel.

PURPOSE: The aim of this in vitro study was to investigate the effectiveness of a novel charcoal-containing whitening toothpaste and a mouthwash on tooth color change and the alterations of enamel that may be induced after toothbrushing, corresponding to a 90-day period. MATERIALS AND METHODS: Forty human canines were used, stained with coffee, and divided into four groups (n = 10) as follows: Group 1 (control) submitted to toothbrushing with deionized water, Group 2 with a regular toothpaste, Group 3 with a whitening toothpaste (1% charcoal), and Group 4 with the same whitening toothpaste in combination with a mouthwash (1% charcoal and 0.5% H2O2). After the treatments, ΔΕ of the teeth was evaluated using an ultraviolet/Vis spectrophotometer, whereas the changes in surface morphology were observed by means of a confocal microscope. RESULTS: The whitening toothpaste increased significantly ΔΕ (40.5%) compared to the control group (P < 0.001). In addition, the tested whitening toothpaste also increased ΔΕ (17.7%) compared to the regular toothpaste (P = 0.023). The whitening toothpaste presented smoother surfaces after toothbrushing, but more heterogeneous with numerous large craters, whereas the whitening mouthwash did not influence surface morphology changes. CONCLUSIONS: Charcoal-containing toothpastes may enhance the whitening of the teeth, but they should be used carefully due to changes that may induce on enamel. The patients should consult a dental professional for proper use. A charcoal-containing mouthwash in combination with whitening toothpastes probably cannot offer additional whitening effect.

Targeted therapy in oncology patients and skin: Pharmaceutical and dermocosmetic management.

BACKGROUND: Numerous oncology patients who receive targeted therapy suffer from the skin adverse effects induced. Novel agents, that is tyrosine kinase inhibitors and RAS-RAF-MEK-ERK pathway, have given good results in patient survival while decreasing the systemic toxicities in comparison to conventional cytotoxic chemotherapy, but are also related to skin adverse effects. AIMS: In this article, we highlighted the importance of specific pharmaceutical and dermocosmetic management of the untoward events of targeted therapy. CONCLUSION: The combination of Oncodermatology, Psychodermatology, Cosmetic Dermatology, Cosmetic Science, Dermatopharmacology and Aesthetic Science can offer a lot for the prevention or early relief of the cutaneous adverse effects in oncology patients receiving targeted therapy.

Physical Forces May Cause the HoxD Gene Cluster Elongation.

Hox gene collinearity was discovered be Edward B. Lewis in 1978. It consists of the Hox1, Hox2, Hox3 ordering of the Hox genes in the chromosome from the telomeric to the centromeric side of the chromosome. Surprisingly, the spatial activation of the Hox genes in the ontogenetic units of the embryo follows the same ordering along the anterior-posterior embryonic axis. The chromosome microscale differs from the embryo macroscale by 3 to 4 orders of magnitude. The traditional biomolecular mechanisms are not adequate to comprise phenomena at so divergent spatial domains. A Biophysical Model of physical forces was proposed which can bridge the intermediate space and explain the results of genetic engineering experiments. Recent progress in constructing instruments and achieving high resolution imaging (e.g., 3D DNA FISH, STORM etc.) enable the assessment of the geometric structure of the chromatin during the different phases of Hox gene activation. It is found that the mouse HoxD gene cluster is elongated up to 5-6 times during Hox gene transcription. These unexpected findings agree with the BM predictions. It is now possible to measure several physical quantities inside the nucleus during Hox gene activation. New experiments are proposed to test further this model.

Hox Gene Collinearity: From A-P Patterning to Radially Symmetric Animals.

Hox gene collinearity relates the gene order of the Hox cluster in the chromosome (telomeric to centromeric end) with the serial activation of these genes in the ontogenetic units along the Anterior-Posterior embryonic axis. Although this collinearity property is well respected in bilaterians (e.g. vertebrates), it is violated in other animals. The A-P axis is established in the early embryo of the sea urchin. Subsequently, rotational symmetry is superimposed when the vestibula larva is formed. In analogy to the linear A-P case, it is here hypothesized that the circular topology of the ontogenetic modules is associated to the architectural restructuring of the Hox loci where the two discrete ends of the Hox cluster approach each other so that an almost circular DNA contour is created. In the evolutionary process the circular mode undergoes double strand breaks and the generated cluster ends are attached to the open ends of the flanking chromosome. This event may lead to a novel gene ordering associated with an evolutionary innovation. For example, the loss of Hox4 is followed by the formation of a shorter gene circular arrangement. The opening of this contour at the missing Hox4 location and its connection to the chromosomal flanking ends leads to a new diversification namely the creation of the unusual gene order of the sea urchin Hox cluster.

Evolutionary constraints favor a biophysical model explaining hox gene collinearity.

The Hox gene collinearity enigma has often been approached using models based on biomolecular mechanisms. The biophysical model is an alternative approach based on the hypothesis that collinearity is caused by physical forces pulling the Hox genes from a territory where they are inactive to a distinct spatial domain where they are activated in a step by step manner. Such Hox gene translocations have recently been observed in support of the biophysical model. Genetic engineering experiments, performed on embryonic mice, gave rise to several unexpected mutant expressions that the biomolecular models cannot predict. On the contrary, the biophysical model offers convincing explanation. Evolutionary constraints consolidate the Hox clusters and as a result, denser and well organized clusters may create more efficient physical forces and a more emphatic manifestation of gene collinearity. This is demonstrated by stochastic modeling with white noise perturbing the expression of Hox genes. As study cases the genomes of mouse and amphioxus are used. The results support the working hypothesis that vertebrates have adopted their comparably more compact Hox clustering as a tool needed to develop more complex body structures. Several experiments are proposed in order to test further the physical forces hypothesis.

Comparison of models for the collinearity of hox genes in the developmental axes of vertebrates.

Hox gene clusters are very frequent in many animal genomes and their role in development is pivotal. Particularly in vertebrates, intensive efforts have established several properties of Hox clusters. The collinearity of Hox gene expressions (spatial, temporal and quantitative) is a common feature of the vertebrates. During the last decade, genetic engineering experiments have revealed some important facets of collinearity during limb and trunk development in mice. Two models have been proposed to explain all these properties. On one hand the 'two-phases model' makes use of the molecular regulatory mechanisms acting on the Hox genes. On the other hand, the'biophysical model' is based on the signals transduced inside the cell nucleus and the generation of forces which apply on the cluster and lead to a coordinated activation of Hox genes. The two models differ fundamentally and a critical and detailed comparison is presented. Furthermore, experiments are proposed for which the two models provide divergent predictions. The outcome of these experiments will help to decide which of the two models is valid (if any).

Development and validation of an ion-pair RP-HPLC method for the determination of oligopeptide-20 in cosmeceuticals.

Oligopeptide-20 is a growth-factor mimicking peptide used in cosmeceuticals. This article describes the development and validation of an ion-pair reversed-phase liquid chromatography method that allows, after liquid-liquid extraction, the quantification of oligopeptide-20 in cosmetic creams. Chromatographic separation was achieved on a cyanopropyl Hypersil analytical column (100 mm × 2.1 mm i.d., 5 µm particle size), using a mobile phase of acetonitrile-heptafluorobutyric acid (pH=2.5, 9.0 mM) (70:30, v/v) containing 0.045% diethylamine at a flow rate of 0.50 mL min(-1). Ultraviolet (UV) spectrophotometric detection at 225 nm was used. The method had linear calibration curve over the range 1.35-4.95 µg mL(-1) for oligopeptide-20. The intra- and inter-day RSD values were less than 3.3%, while the relative percentage error, %E(r), was less than 1.9. The developed method was applied successfully to the quality control of a cosmetic cream containing 0.003% (w/w) oligopeptide-20.

Physical forces may cause Hox gene collinearity in the primary and secondary axes of the developing vertebrates.

The features of spatial and temporal Hox gene collinearity along the anteroposterior and secondary axes of vertebrate development have been extensively studied. However, the understanding of these features remains problematic. Some genetic engineering experiments were performed and the consequent modifications of the Hoxd gene expressions in the vertebrate limb and trunk were presented. A two-phases model was proposed to describe the above results but still many data cannot be explained. In the present work a different mechanism is put forward in order to deal with the above experiments. This alternative mechanism (coined biophysical model), is based on the hypothesis that physical forces decondense and 'loop out' the chromatin fiber causing the observed Hox gene collinearity phenomena at the early stages of axonal development. The two models are compared in detail. The biophysical model adequately explains the data even in cases where the results are characterized as unexpected. Furthermore, the biophysical model predicts that the Hox gene expressions are entangled in space and time and this coupling is compatible with the data of the early developmental stages. Additional experiments are proposed for a direct test of this model.

A biophysical mechanism may control the collinearity of Hoxd genes during the early phase of limb development.

A biophysical model has been proposed which deals with the observed collinearity of Hox gene expressions in developing vertebrate limbs. It is assumed that physical forces gradually dislocate the genes of the Hoxd cluster from inside the chromosome territory into the interchromosome domain, where the genes are activated. In particular, the action of Coulomb electric forces has been estimated in detail. Genetic engineering experiments (deletions, duplications and transpositions) were recently reported for Hoxd expression during limb development. Here, we analyse these results and show that the biophysical model explains them successfully.

Pulling forces acting on Hox gene clusters cause expression collinearity.

The development of normal patterns along the primary and secondary vertebrate axes depends on the regularity of early Hox gene expression. During initial stages, these expression events form a sequential pattern of partially overlapping domains along the anteroposterior axis in coincidence with the 3' to 5' order of the genes in the Hox cluster (spatial collinearity). In addition, the genes are activated one after the other in the 3' to 5'order (temporal collinearity). These features are poorly understood within the framework of Molecular Genetics. A model was proposed according to which physical forces act on Hox clusters as a result of signaling from morphogen gradients. The model can explain the collinearity of Hox gene expression along the primary and secondary body axes. The increase in the concentration of morphogen is accordingly followed by an increase of the force acting on the cluster. The genes are sequentially translocated, in the 3' to 5' order, toward the interchromosome domain where they are exposed to transcription factors for activation. The above geometrodynamic approach reproduces most collinearity data. Recent experiments verify the above prediction of sequential 3' to 5' Hox gene translocations in the interchromosome domain. Furthermore, it seems that these translocations, combined with cluster decondensations, are caused by attractive forces acting on the 3' end of the cluster and pulling the genes out of the chromosome territory. Additional experiments are proposed in order to specify the origin of the forces.

A cluster translocation model may explain the collinearity of Hox gene expressions.

A model is proposed that deals with the observed collinearities (spatial, temporal and quantitative) of Hox gene expression during pattern formation along the primary and secondary axes of vertebrates. In particular, in the proximodistal axis of the developing limb, it is assumed that a morphogen gradient is laid down with its source at the distal tip of the bud. The extracellular signals in every cell of the morphogenetic field are transduced and uniformly amplified so that molecules are produced in the nucleus with appropriate physicochemical properties. These molecules can exert a concentration-dependent force on the Hox cluster. It is assumed that, before activation, the Hox cluster is packaged as an elongated rigid body inside the chromatin and is covered by a coat that prevents the transcription factors reaching the genes of the cluster. The transcription factors are confined to the interchromatin domain and their density decreases with their distance from the chromatin surface. A gradual increase in the extracellular morphogen concentration causes a corresponding increase in the number of the nuclear molecules and the resulting bigger force pushes the Hox cluster toward the interchromatin domain. The step-by-step translocations of the Hox cluster initiate the consecutive exposure of genes to their transcription factors. The model explains how gene activation is triggered and it describes spatial, temporal and quantitative collinearities at the initial stages of gene expression. Some recent experiments of Hox deletions and duplications are accounted for by the model.