Gehring-Hayman theorem for conformal deformations

We study conformal deformations of a uniform space that satisfies the Ahlfors Q-regularity condition on balls of Whitney type. We verify the Gehring–Hayman Theorem by using a Whitney Covering of the space.

Assessment of the potential skin irritation of lysine-derivative anionic surfactants using mouse fibroblast and human keratinocytes as an alternative to animal testing

Purpose. The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants. Methods. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6, and the human keratinocyte cell line NCTC 2544, using the MTT assay and uptake of the vital dye neutral red 24 h after dosing (NRU). Results. Lysine-derivative surfactants showed higher IC50s than did commercial anionic irritant compounds such as sodium dodecyl sulphate, proving to be no more harmful than amphoteric betaines. The aggressiveness of the surfactants depended upon the size of their constituent counterions: surfactants associated with lighter counterions showed a proportionally higher aggressivity than those with heavier ones. Conclusions. Synthetic lysine-derivative anionic surfactants are less irritant than commercial surfactants such as sodium dodecyl sulphate and Hexadecyltrimethylammonium bromide and are similar to Betaines. These surfactants may offer promising applications in pharmaceutical and cosmetic preparations, representing a potential alternative to commercial anionic surfactants as a result of their low irritancy potential.

Comparative sensitivity of tumor and non-tumor cell lines as reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC50-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

The curcumin analog DM-1 induces apoptotic cell death in melanoma

The main difficulty in the successful treatment of metastatic melanoma is that this type of cancer is known to be resistant to chemotherapy. Chemotherapy remains the treatment of choice, and dacarbazine (DTIC) is the best standard treatment. The DM-1 compound is a curcumin analog that possesses several curcumin characteristics, such as antiproliferative, antitumor, and antimetastatic properties. The objective of this study was to evaluate the signaling pathways involved in melanoma cell death after treatment with DM-1 compared to the standard agent for melanoma treatment, DTIC. Cell death was evaluated by flow cytometry for annexin V and iodide propide, cleaved caspase 8, and TNF-R1 expression. Hoechst 33342 staining was evaluated by fluorescent microscopy; lipid peroxidation and cell viability (MTT) were evaluated by colorimetric assays. The antiproliferative effects of the drugs were evaluated by flow cytometry for cyclin D1 and Ki67 expression. Mice bearing B16F10 melanoma were treated with DTIC, DM-1, or both therapies. DM-1 induced significant apoptosis as indicated by the presence of cleaved caspase 8 and an increase in TNF-R1 expression in melanoma cells. Furthermore, DM-1 had antiproliferative effects in this the same cell line. DTIC caused cell death primarily by necrosis, and a smaller melanoma cell population underwent apoptosis. DTIC induced oxidative stress and several physiological changes in normal melanocytes, whereas DM-1 did not significantly affect the normal cells. DM-1 antitumor therapy in vivo showed tumor burden decrease with DM-1 monotherapy or in combination with DTIC, besides survival rate increase. Altogether, these data confirm DM-1 as a chemotherapeutic agent with effective tumor control properties and a lower incidence of side effects in normal cells compared to DTIC.

Oral findings in Midline Syndrome: a case report and literature review

We describe a female patient with a midline syndrome. The patient presents agenesis of the corpus callosum, encephalocele, iris coloboma, hypertelorism, submucosal cleft palate and dental anomalies. Despite being very characteristic, her phenotypical traits do not coincide exactly with those reported to date in the literature. The karyotype and the molecular cytogenetic study do not show mutations. We identify the presence of dental anomalies in the mother and other family members, not being identified MSX1 and PAX9 mutations that could the related with their etiology. Despite the fact that dental agenesis has been related to a large number of other malformation syndromes and congenital conditions, dental anomalies have only rarely been mentioned when reporting midline syndromes. These dental phenotypical traits, present in the patient and her family, could be considered part of the midline syndrome in carriers as well as in the patients.

An epidemiological study of dental agenesis in a primary health area in Spain: estimated prevalence and associated factors

Objectives: To evaluate the prevalence of dental agenesis and its possible association with other developmental dental anomalies and systemic entities. Setting and Sample Population: Descriptive transversal study, for which 1518 clinical records, of patients visited by the Odontological Service of the Primary Health Centre of Cassà de la Selva (Girona-Spain) between December 2002 and February 2006 were reviewed. The data were recorded in relation to the oral and dental anomalies and the associated systemic entities, between the ones referred as concomitant in literature. Results: Values of 9.48% (7.25% excluding the third molars) for dental agenesis and 0.39% for oligodontia were obtained. The presence of dental agenesis concomitant with some other forms of oral and dental anomalies was observed. Attention must be drawn to the fact that a greater number of concomitant systemic entities were observed in those patients that presented a severe phenotypical pattern of dental agenesis. Conclusions: The results of the present study do not differ from the ones reported in studies of similar characteristics among Occidental and Spanish populations. The relationship observed between certain systemic entities and developmental dental anomalies suggest a possible common genetic etiology

Unraveling the "pressure effect" in nucleation

The influence of the pressure of a chemically inert carrier gas on the nucleation rate is one of the biggest puzzles in the research of gas-liquid nucleation. Experiments can show a positive effect, a negative effect, or no effect at all. The same experiment may show both trends for the same substance depending on temperature, or for different substances at the same temperature. We show how this ambiguous effect naturally arises from the competition of two contributions: nonisothermal effects and pressure-volume work. Our model clarifies seemingly contradictory experimental results and quantifies the variation of the nucleation ability of a substance in the presence of an ambient gas. Our findings are corroborated by molecular dynamics simulations and might have important implications since nucleation in experiments, technical applications, and nature practically always occurs in the presence of an ambient gas.