Unexpected clobetasol propionate profile in human stratum corneum after topical application in vitro

Purpose. The validity of using drug amount-depth profiles in stratum corneum to predict uptake of clobetasol propionate into stratum corneum and its transport into deeper skin layers was investigated. Methods. In vitro diffusion experiments through human epidermis were carried out using Franz-type glass diffusion cells. A saturated solution of clobetasol propionate in 20% (V/V) aqueous propylene glycol was topically applied for 48 h. Steady state flux was calculated from the cumulative amount of drug permeated vs. time profile. Epidermal partitioning was conducted by applying a saturated drug solution to both sides of the epidermis and allowing time to equilibrate. The tape stripping technique was used to define drug concentration-depth profiles in stratum corneum for both the diffusion and equilibrium experiments. Results. The concentration-depth profile of clobetasol propionate in stratum corneum for the diffusion experiment is biphasic. A logarithmic decline of the drug concentration over the first four to five tape strips flattens to a relatively constant low concentration level in deeper layers. The drug concentration-depth profile for the equilibrium studies displays a similar shape. Conclusions. The shape of the concentration-depth profile of clobetasol propionate is mainly because of the variable partitioning coefficient in different stratum corneum layers.

χ-conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter

The interactions of chi-conopeptide MrIA with the human norepinephrine transporter (hNET) were investigated by determining the effects of hNET point mutations on the inhibitory potency of MrIA. The mutants were produced by site-directed mutagenesis and expressed in COS-7 cells. The potency of MrIA was greater for inhibition of uptake by hNET of [H-3] norepinephrine (K-i 1.89 muM) than [H-3] dopamine (K-i 4.33 muM), and the human dopamine transporter and serotonin transporter were not inhibited by MrIA ( to 7 muM). Of 18 mutations where hNET amino acid residues were exchanged with those of the human dopamine transporter, MrIA had increased potency for inhibition of [H-3] norepinephrine uptake for three mutations ( in predicted extracellular loops 3 and 4 and transmembrane domain (TMD) 8) and decreased potency for one mutation (in TMD6 and intracellular loop (IL) 3). Of the 12 additional mutations in TMDs 2, 4, 5, and 11 and IL1, three mutations (in TMD2 and IL1) had reduced MrIA inhibitory potency. All of the other mutations tested had no influence on MrIA potency. A comparison of the results with previous data for desipramine and cocaine inhibition of norepinephrine uptake by the mutant hNETs reveals that MrIA binding to hNET occurs at a site that is distinct from but overlaps with the binding sites for tricyclic antidepressants and cocaine.

Expression of hNP22 is altered in the frontal cortex and hippocampus of the alcoholic human brain

Background: Human neuronal protein (hNP22) is a gene with elevated messenger RNA expression in the prefrontal cortex of the human alcoholic brain. hNP22 has high homology with a rat protein (rNP22). These proteins also share homology with a number of cytoskeleton-interacting proteins. Methods: A rabbit polyclonal antibody to an 18-amino acid epitope was produced for use in Western and immunohistochemical analysis. Samples from the human frontal and motor cortices were used for Western blots (n = 10), whereas a different group of frontal cortex and hippocampal samples were obtained for immunohistochemistry (n = 12). Results: The hNP22 antibody detected a single protein in both rat and human brain. Western blots revealed a significant increase in hNP22 protein levels in the frontal cortex but not the motor cortex of alcoholic cases. Immunohistochemical studies confirmed the increased hNP22 protein expression in all cortical layers. This is consistent with results previously obtained using Northern analysis. Immunohistochemical analysis also revealed a significant increase of hNP22 immunoreactivity in the CA3 and CA4 but not other regions of the hippocampus. Conclusions: It is possible that this protein may play a role in the morphological or plastic changes observed after chronic alcohol exposure and withdrawal, either as a cytoskeleton-interacting protein or as a signaling molecule.

Potential for early involvement of CYP isoforms in aspects of human cadmium toxicity

This paper investigates the possible link between non-workplace cadmium (Cd) exposure, cytochrome P450 expression and hypertension. We present results of our investigation into the relationships between liver and kidney Cd burdens and the abundance of the CYP isoform 4A11. Our data show associations between non-workplace Cd exposure and changes in the abundance of hepatic and renal cortical CYP4A11. In liver the levels of immunochemically detectable CYP4A11 were positively correlated with tissue Cd content while in contrast CYP4A11 abundance was inversely correlated with kidney Cd burden. These differences are most likely related to the different Cd burden of the tissues. These observations suggest the potential for involvement of Cd as a mediator of CYP4A11 expression in kidney cortex and indicate that elevations in kidney Cd content may be involved in hypertension via alteration of the expression of this particular isoform. Potential mechanisms by which Cd may alter CYP4A11 expression are discussed briefly. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B(RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen

The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.

The Utility of the Human Security Agenda for Policy-makers

The idea of “human security” is gaining attention among policy-makers and security analysts. Little scholarly attention has been given to the questions of why states accept (or reject) a human security agenda or how such an agenda is incorporated into policy practices. The article suggests that a human security approach is most likely to be applied when both humanitarian and national interests combine. Yet when states or organisations adopt a human security approach, they often misjudge the complex and long-term commitment required of such an approach. There is also the potential for such an agenda to be manipulated to justify questionable courses of action. These issues frame an analysis of six recent case studies.

An optical flow-based sensing system for reactive mobile robot navigation

This work discusses the use of optical flow to generate the sensorial information a mobile robot needs to react to the presence of obstacles when navigating in a non-structured environment. A sensing system based on optical flow and time-to-collision calculation is here proposed and experimented, which accomplishes two important paradigms. The first one is that all computations are performed onboard the robot, in spite of the limited computational capability available. The second one is that the algorithms for optical flow and time-to-collision calculations are fast enough to give the mobile robot the capability of reacting to any environmental change in real-time. Results of real experiments in which the sensing system here proposed is used as the only source of sensorial data to guide a mobile robot to avoid obstacles while wandering around are presented, and the analysis of such results allows validating the proposed sensing system.

Uprootedness and the protection of migrants in the International Law of Human Rights

The article attempt to demonstrate the evolution of international law in connected to the subject of the forced immigrants'. The author supported by several texts, cases and resolutions of the regional level, through interamerican court and European court, and the global level, through the international court. It's shown the evolution that occurred in international law in millennium turn over, which recognize the immigrants' rights. However, it's stressed the necessity of the development of those laws connected to the theme e the recognition, from the States; the importance of law's that effort to ensure the respect to human rights relative to the immigrants and their families.

Human Rights promotion in Serbia: a difficult task for the European Union

This article explores the role of the European Union in the human rights protection, implementation and promotion in Serbia. It is clear that the EU demands on democratisation in the region of Western Balkans are crucial to achieve the respect for human rights. The human rights standards as part of the conditionality criteria of the EU is a clear message towards the countries aspiring membership. However, Serbia progress in the field has been difficult due to several internal constraints. This paper aims to uncover the democratisation process of Serbia on its path towards the EU, and its progress (or not) regarding human rights protection and implementation.

Economic sanctions and human rights: an analysis of competing enforcement strategies in Latin America

This article addresses the consequences of economic sanctions for the protection of human rights in Latin America. The literature on sanctions and compliance informs three hypotheses, which investigate the relationship between sanctions and the level of rights protection in two groups of countries: those that were targeted by sanctions and those that were not. Using data from the Political Terror Scale (PTS) and from Freedom House, I find empirical evidence that sanctions do improve the level of protection in countries that were not targeted. This finding can be explained by the deterrent effect attributed to sanctions by the compliance literature, broadly interpreted. The presence of economic sanctions in a given year increases the probability of observing better human rights practices by almost 50%. These results hold for the 12 Latin American countries that were not subject to economic sanctions for the period 1976-2004.

Prevalence of periodontal disease in dogs and owners' level of awareness - a prospective clinical trial

Periodontal disease (PD) is widely known among veterinarians for its high prevalence and serious consequences to the dogs. The objective of this study was to assess the occurrence of PD in dogs that live in the micro-region of Viçosa, treated at the Veterinary Hospital of the Federal University of Viçosa (HVT - Hospital Veterinário da Universidade Federal de Viçosa), as well as to assess how aware of this disease dog owners are. In order to do so, all dogs treated at the HVT from March 10th, 2009 to November 30th, 2009, on alternate days, had their oral cavities examined. Medical history data, such as age, type of food, main complaint and owner consent, halitosis, presence of dental calculus, inflammation and gingival recession and tooth loss, were collected. A prevalence of 88.67% was found for PD in dogs referred to the HVT, and 2.67% were referred due to this disease. Of all the owners who participated in the study, 43.83% knew about periodontal disease and of these 17.46% made use of some type of prevention or treatment. Therefore, periodontal disease is highly prevalent and the owners are not aware of the disease. Thus, a dog owner clarification program on periodontal disease is needed in the area where HVT-UFV operates.

Do we need a “new” international convention that helps to avoid trafficking in organs? Some “criminal (and civil) law aspects” - Convention on Human Rights and Biomedicine – updated or outdated?

Abstract: § 1 «Do we need a “new” international convention that helps to avoid trafficking in organs? Some criminal (and civil) law aspects”» - «Convention on Human Rights and Biomedicine – updated or outdated?». § 2 Some important connections: on the one hand, between the 1997 Council of Europe Convention on Human Rights and Biomedicine; the 2002 Additional Protocol to the Convention on Human Rights and Biomedicine concerning Transplantation of Organs and Tissues of Human Origin; and, on the other hand, the problem of trafficking in organs, tissues and cells and trafficking in human beings for the purpose of the removal organs. Some connections. § 3 The «international undisputed principle». § 4 Trafficking in organs, tissues and cells; and trafficking in human beings for the purpose of the removal organs. Criminal Law and Civil Law. § 5 Promote organ donation. § 6 The necessity to collect reliable data on both trafficking cases. § 7 The necessity for an internationally agreed definition of trafficking in OTC: Convention on Human Rights and Biomedicine – updated or outdated? § 8 The (inter)national and (il)legal organ («tissue and cell») trade: some cases and some conclusions. § 9 Do we need a new international convention to prevent trafficking in organs, tissues and cells (OTC)? § 10 Of course we need a «new» international convention to prevent trafficking in organs, tissues and cells (OTC). § 11 At the present moment, we do not need a «new» international convention to prevent trafficking in human beings for the purpose of the removal organs. § 12 The Portuguese case. § 13 «Final conclusions.» § Resumo: § 1 «Precisamos de uma "nova" convenção internacional que ajude a evitar o tráfico de órgãos? Alguns aspectos de lei criminal (e civil)» - «Convenção sobre Direitos Humanos e Biomedicina - Actualizada ou desactualizada?». § 2 Algumas conexões importantes: por um lado, entre a Convenção do Conselho da Europa de 1997 sobre Direitos Humanos e Biomedicina; o Protocolo Adicional de 2002 à Convenção sobre os Direitos do Homem e da Biomedicina relativo ao transplante de órgãos e tecidos de origem humana, e, por outro lado, o problema do tráfico de órgãos, tecidos e células e tráfico de seres humanos para fins de remoção dos órgãos. § 3 O «indiscutível princípio internacional». § 4 O Tráfico de órgãos, tecidos e células; e o tráfico de seres humanos para fins de remoção dos órgãos. Direito Penal e Direito Civil. § 5 Promover a doação de órgãos. § 6 A necessidade de colectar dados fidedignos sobre os dois casos de tráfico. § 7 A necessidade de uma definição internacionalmente acordada de tráfico de OTC: Convenção sobre Direitos Humanos e Biomedicina - actualizada ou desactualizada? § 8 A (inter)nacional e (il)legal comercialização de órgãos («de tecidos e de células»): alguns casos e algumas conclusões. § 9 Será que precisamos de uma nova convenção internacional para prevenir o tráfico de órgãos, tecidos e células (OTC)? § 10 É claro que precisamos de uma «nova» convenção internacional para prevenir o tráfico de órgãos, tecidos e células (OTC). § 11 No presente momento, não precisamos de uma «nova» convenção internacional para impedir o tráfico de seres humanos para fins de remoção dos órgãos. § 12 O caso Português. § 13 «As conclusões finais.»

Capital Intelectual: sua divulgação no setor bancário em Portugal

The importance of intangible resources has increased dramatically in recent years comparing to tangible ones. The economy in which we live is the result of competitive pressures that have imposed the implementation of business at an international level as well as a requirement in the application of sophisticated technologies that allow us to follow this fast evolution. In this age of information and innovation organizations will only survive if they are inserted in a global network of strategic relations, generically called as the network economy by Lev (2003). The service sector has stood out against the more traditional sectors of the economy. The intensive use of knowledge and a strong customer orientation created a new reality in today’s organizations: a growing importance attached to innovation, to the quality of products and services offered, to the information and communication technologies adopted, and to the creativity and particular abilities of human resources. The concept of intangible assets is more common in an accounting language and intellectual capital is most often applied in the context of management, being associated with a more comprehensive, multidimensional approach, representing all the knowledge that the institution owns and that it applies in the form of expertise, the creativity and organizational competencies that lead to innovation and to the sustained attainment of future economic benefits. An analysis of the scope of intellectual capital is fundamental to take more appropriate management decisions so that a more appropriate accounting treatment could be given by the accounting standardization organizations. This study intends to analyse the practices of information disclosure of the intellectual capital in the banking sector in Portugal, complementing the analysis of the disclosure of intangible assets in the context of accounting standards with the disclosure of intellectual capital in the context of organizational management. In particular, our main aims are to identify the extent of disclosure of intellectual capital made by banks in Portugal and also to identify the factors that determine such a disclosure. The disclosure in the context of accounting standards will be studied by checking the disclosure of intangible assets through the items listed in the International Accounting Standard 38 developed by the International Accounting Standards Board. The context of management was analysed by means of creating a voluntary disclosure index based on assumptions of the model Intellectus, developed by the Centro de Investigación sobre la Sociedad del Conocimiento – Instituto de Administración de Empresas (CIC-IADE) of the Universidad Autónoma of Madrid, and of the model Intellectual Capital Statement (made in Europe) (InCaS), both promoted by the European Commission and that we have adapted to the banking sector. When analysing the disclosure of intangible assets based on the context of accounting standards and the voluntary disclosure of intellectual capital, this study has tried to raise awareness about the importance of issuing reports on the intellectual capital as an alternative tool to take management decisions in the existing organizations and reflects the transparency and legitimacy that these institutions seek through a more extensive and more detailed information disclosure of their intellectual capital. Based on a complimentarily of economic theories, together with social and political theories, we tried to check the extent, evolution and tendencies of the compulsory disclosure of intangible assets and of the voluntary disclosure of the intellectual capital analysed in the period 2001-2011. Banks characteristics were also analysed in order to deduce those factors that determine or promote a larger disclosure in this sector. Based on these objectives, we adopted a longitudinal approach to explore the extent and the development of the disclosure of intangible assets as well as the factors that have determined it. Furthermore, we sought to assess the impact of the adoption of IAS 38 in the financial statements of the organizations in this sector. The disclosure index created on the basis of the disclosure requirements stated in IAS 38 from IASB was applied to the consolidated financial statements of the seventeen banks that rendered their statements in Portugal from 2001 to 2009. Since the information disclosed in the context of accounting standards may not have an important role as a management tool once it was not able to reflect what really contributes to the competitiveness and organizational growth, the voluntary disclosure of the intellectual capital was analysed according to the information obtained from the 2010 annual individual reports of the banks operating in Portugal in that year and from their respective websites in 2011. We tried to analyse the extent of the voluntary disclosure of the intellectual capital and of each of its components, human capital, structural capital and relational capital. The comparative analysis of their annual reports and their web pages allowed us to assess the incidence of the disclosure and discover what channel the banking sector focuses on when disclosing their intellectual capital. Also in this analysis the study of the disclosure determinants has allowed us to conclude about the influence of particular characteristics in the voluntary disclosure of the intellectual capital. The results of the analysis to the extent of the disclosure of intangible assets in the consolidated financial statements of the banking groups in Portugal in the period 2001-2009 have shown an average information disclosure of 0.24. This information disclosure evolved from an average value of 0.1940 in 2001 to 0.2778 in 2009. The average value is 0.8286 if it is only considered the disclosure of the intangible assets that the banks possessed. The evolution of this index means an increase in the average disclosure from 0.7852 in 2001 to 0.8788 in 2009. From the first results that are related to the extent of the disclosure of intangible assets in the financial statements, we can verify that the banking groups present a low disclosure level of these resources. However, when considering the disclosure of only the intangible assets that each institution owns, the disclosure level appears to be in compliance with the disclosure requirements for this sector. An evolution in the disclosure of intangible assets for the period considered was confirmed, showing an increase in the information disclosure of intangible assets in 2005, the year in which the accounting rules for intangible assets changed. The analysis that focused on the disclosure in the context of management tried to understand the extent, the incidence and the determinants of the voluntary information disclosure of intellectual capital in the annual reports of 2010 and on their web pages in 2011, studying the 32 banks operating in Portugal in this period. The average voluntary disclosure of the intellectual capital in the 2010 annual reports is 0.4342 while that in web pages is 0.2907. A review of the components of the intellectual capital allowed us to assess the importance that the banks confer to each of these components. The data obtained show that the relational capital, and more specifically the business capital, is the most disclosed component by banks in Portugal both in the annual reports and in their institutional web pages, followed by the structural capital and, finally, by the human capital. The disclosure of the human capital and the structural capital is higher in the annual reports than that in the websites, while the relational capital is more disclosed in the websites than in the annual reports. The results have also shown that the banks make a complementary use of both sources when disclosing information about their structural capital and relational capital but they do not show any information about their human capital in their websites. We tried to prove the influence of factors that could determine the accounting disclosure and the voluntary disclosure of the intellectual capital in this sector. The change in the IASB accounting rules as from January 1st 2005 gave a greater disclosure of accounting information of intangible assets in the financial statements of banks. The bank size and corporate governance measures have statistically proved to have an influence on the extent of the accounting disclosure of intangible assets and on the voluntary disclosure of the intellectual capital. Economic and financial variables such as profitability, operating efficiency or solvency were not determinants of information disclosure. The instability that the banking sector has experienced in economic and financial indicators in recent years as a result of the global financial markets imbalance has worsen indicators such as profitability, efficiency and solvency and caused major discrepancies in the economic situation between banks in Portugal. This empirical analysis has contributed to confront the disclosure required by accounting rules performed in the financial statements of organizations with that performed in the main disclosure media which is available for entities and which is increasingly requested in the process of taking management decisions. It also allowed us to verify whether there is homogeneity between institutions in the fulfilment of the requirements for information disclosure of intangible assets. However, as for voluntary disclosure of intellectual capital, there are large disparities in the disclosure extent between organizations. Regardless of this sector specific characteristics, the voluntary disclosure of intellectual capital made by banks in Portugal follows the trends in other sectors and the practices adopted in other countries, namely regarding the amount of information disclosed, the incidence of the disclosure on the indicators of relational capital and the importance of variables such as size as determinants of disclosure of intellectual capital. For a further knowledge in this field, we created a specific index for the banking sector, considering appropriate indicators for an incisive, comprehensive analysis in order to consider the most relevant indicators of intellectual capital components. Besides, confronting the analysis of disclosure in the context of accounting standards with the study of voluntary disclosure brought a new analysis approach to the research on intellectual capital disclosure. With this study, we have also intended to raise greater awareness of the need for harmonization in the intellectual capital disclosure on the part of the regulatory banking authority by means of a demanding, consistent and transparent report of intellectual capital with simple, clear, objective indicators so that those interested in disclosing intellectual capital information in the organizations in this sector may obtain more harmonized and comparable information. A research on the disclosure quality of intellectual capital, together with the application of other analysis methodologies in this sector, might be a promising approach for future research. Applying the voluntary disclosure index to the same sector in other countries may also contribute to the knowledge of disclosure practices in different geographical environments. We highlight the relevance of further studies contributing to the harmonization and consistency in the presentation of an intellectual capital report so as to enable organizations to disclose the resources that contribute most to their competitiveness and growth.

Mechatronic system for ABO human blood typing

In medical emergency situations, when a patient needs a blood transfusion, the universal blood type O− is administered. This procedure may lead to the depletion of stock reserves of O− blood. Nowadays, there is no commercial equipment capable of determining the patient's blood type in situ, in a fast and reliable process. Human blood typing is usually performed through the manual test, which involves a macroscopic observation and interpretation of the results by an analyst. This test, despite of having a fast response time, may lead to human errors, which sometimes can be fatal to the patient. This paper presents the development of an automatic mechatronic prototype for determining human blood typing (ABO and Rh systems) through image processing techniques. The prototype design takes into account the characteristics of reliability of analysis, portability, and response time allowing the system to be used in emergency situations. The developed prototype performs blood and reagents mixture acquires the resultant image and processes the data (based on image processing techniques) to determine the sample blood type. It was tested in a laboratory, using cataloged samples of blood types, provided by the Portuguese Institute of Blood and Transplantation. Hereafter, it is expected to test and validate the prototype in clinical environments.