Carbenoxolone does not cross the blood brain barrier: an HPLC study

BACKGROUND: Carbenoxolone (CBX) is a widely used gap junctional blocker. Considering several reports indicating that transient gap junctional blockade could be a favourable intervention following injuries to central nervous tissue, and some current enthusiasm in studies using systemic injections of CBX, it is imperative to consider the penetration of CBX into central nervous tissue after systemic administrations. So far, only very indirect evidence suggests that CBX penetrates into the central nervous system after systemic administrations. We thus determined the amounts of CBX present in the blood and the cerebrospinal fluid of rats after intraperitoneal administration, using high performance liquid chromatography RESULTS: CBX was found in the blood of the animals, up to 90 minutes post-injection. However, the cerebrospinal fluid concentration of CBX was negligible. CONCLUSION: Thus, we conclude that, most likely, CBX does not penetrate the blood brain barrier and therefore recommend careful consideration in the manner of administration, when a central effect is desired

Phylogenetically Diverse Mesorhizobium Strains: Effect in the Root Colonization and Development of Tomato Seedlings.

Mesorhizobium contains species widely known as nitrogen-fixing bacteria with legumes, but their ability to promote the growth of non-legumes has been poorly studied. Here, we analyzed the production of indole acetic acid (IAA), siderophores and the solubilization of phosphate and potassium in a collection of 24 strains belonging to different Mesorhizobium species. All these strains produce IAA, 46% solubilized potassium, 33% solubilize phosphate and 17% produce siderophores. The highest production of IAA was found in the strains Mesorhizobium ciceri CCANP14 and Mesorhizobium tamadayense CCANP122, which were also able to solubilize potassium. Moreover, the strain CCANP14 showed the maximum phosphate solubilization index, and the strain CCANP122 was able to produce siderophores. These two strains were able to produce cellulases and cellulose and to originate biofilms in abiotic surfaces and tomato root surface. Tomato seedlings responded positively to the inoculation with these two strains, showing significantly higher plant growth traits than uninoculated seedlings. This is the first report about the potential of different Mesorhizobium species to promote the growth of a vegetable. Considering their use as safe for humans, animals and plants, they are an environmentally friendly alternative to chemical fertilizers for non-legume crops in the framework of sustainable agricultur

Pranlukast Antagonizes CD49f and Reduces Sternness in Triple-Negative Breast Cancer Cells

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clini-cally tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces con-formational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transacti-vation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients

La Problematización: Herramienta para facilitar el aprendizaje auténtico de las ciencias en el nivel elemental

This article presents how the problematization, which was facilitated through the Life’s Replica Project, served as a context for sixth grade students to learn about ecology in an authentic way. It describes how through different activities conducted during one semester, in and out of the classroom, students experienced authentic learning that helped them become aware of their environmental impact and their role in society. The core activities of the project were divided into: a) activities to facilitate problematization, b) learning activities, and c) activities to apply what was learned. Through this project, students investigated a problem, developed a product, and provided a service to their community. Finally, the most important achievements of the project are presented. In conclusion, the problematization is a useful tool to facilitate authentic science learning at the elementary level.En este artículo se presenta cómo la problematización, que se facilitó por medio del Proyecto Réplicas para la Vida, sirvió de contexto para que estudiantes de sexto grado aprendieran de manera auténtica acerca de ecología. Se describe cómo a través de diferentes actividades realizadas durante un semestre, dentro y fuera del salón de clases, los estudiantes experimentaron un aprendizaje auténtico que les ayudó a tomar conciencia de su impacto ambiental y su rol en la sociedad. Las actividades medulares del proyecto se dividieron en: a) actividades para facilitar la problematización, b) actividades de aprendizaje y c) actividades para aplicar lo aprendido. A través de este proyecto los estudiantes investigaron un problema, desarrollaron un producto y prestaron un servicio a su comunidad. Finalmente, se presentan los logros más importantes del proyecto. Se concluye que la problematización es una herramienta útil para facilitar el aprendizaje auténtico de las ciencias en el nivel elemental. &nbsp

Estimation of coupling between oscillators from short time series via phase dynamics modeling: limitations and application to EEG data

We demonstrate in numerical experiments that estimators of strength and directionality of coupling between oscillators based on modeling of their phase dynamics [D.A. Smirnov and B.P. Bezruchko, Phys. Rev. E 68, 046209 (2003)] are widely applicable. Namely, although the expressions for the estimators and their confidence bands are derived for linear uncoupled oscillators under the influence of independent sources of Gaussian white noise, they turn out to allow reliable characterization of coupling from relatively short time series for different properties of noise, significant phase nonlinearity of the oscillators, and non-vanishing coupling between them. We apply the estimators to analyze a two-channel human intracranial epileptic electroencephalogram (EEG) recording with the purpose of epileptic focus localization.Comment: 22 pages, 7 figures, the paper is to be published in Chaos, 2005, vol.15, issue 2, see http://chaos.aip.org

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents

Periodontal Disease and Nuclear and Oxidative DNA Damage

Oral health is an important aspect of the overall health status of an individual. DNA damage has been associated with oral health and dental factors due to the increased of oxidative stress (OxS). DNA damage can produce a wide range of effects on human health. These effects could appear immediately, but others do not become evident much later. Chronic diseases have been study to understand their mechanisms, clinical implications, and the development of secondary disease such as cancer. Periodontitis is one of the most common oral diseases. It is an inflammatory chronic infectious disease, which is characterized by the loss of supporting tissues and tooth loss caused by periodontopathogens and long-term release of reactive oxygen species (ROS); thus, oxidative stress is increased during periodontitis. Oxidative stress can produce DNA damage, including the oxidation of nucleosides, which could cause DNA strand break. This oxidative damage leads the formation of micronuclei (MN) a marker of nuclear damage. Also, oxidative stress increased 8-hydroxy-2′-deoxyguanosine levels which are the most common stable product of oxidative DNA damage

Sustainability Assessment of Alternatives for Heat Generation and Transfer in Saunas

Abstract In the search for renewable energy sources, solar energy appears, among others, as a powerful alternative; mainly for those countries located at Earth's equatorial region. This is the case of a Fresnel device that uses solar radiation to warm-up the air; for instance, within saunas. Authors coined the term sustainable technological innovation to refer to a technological innovation in accordance to the principles of sustainability. The object of this research was comparing the sustainability of a Fresnel Lens Solar Concentration (FLSC) against the sustainability of other twelve alternatives to generate heat. This article assesses the sustainability of fourteen technological options for heat generation and transfer to saunas in the northwest region of Mexico where temperatures often reach above 45 C and where there is a greater potential for exploiting solar energy. Emergy accounting, economic analysis, and global warming potential are the three indicators considered in quantifying sustainability. Results show that infrared ceramic photovoltaic, infrared carbon photovoltaic and infrared metal photovoltaic are the most sustainable systems. The Fresnel device reached the fourth and tenth position, using electricity from photovoltaic and from grid respectively, among all fourteen assessed devices, respectively. Although Fresnel equipment does not release any global warming gases into the atmosphere, or even it demands low amount of nonrenewable resources, 1.40 and 4.47 E17 seJF/yr. it requires high economic investment, 20,800 and 79,600 USD/yr, for the implementation and operation phases, which decrease its sustainability performance compared to twelve other evaluated devices