Comparative Bioavailability Study of Two 81 mg Coated Tablet Formulations of Acetylsalicylic Acid in Fasting Healthy Volunteers

Introduction: Low-dose acetylsalicylic acid is used as antithrombotic agent and the enteric-coated formulations are widely used to minimize the gastrointestinal side effects. Aim: To compare the bioavailability of two acetylsalicylic acid formulations (Ecasil-81®, 81 mg coated tablet) in fasting healthy volunteers. Methods: Healthy volunteers (n=16) were recruited to a monocentric, open label, randomized, two-way crossover pharmacokinetic study, with seven days washout period between the treatments. They received a single 81 mg oral dose of a test (new formulation) or a standard reference formulation of acetylsalicylic acid (Ecasil-81®) after about 8 h fasting. Blood samples were collected over a period of 36 h. The salicylic acid plasma concentration was evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Noncompartmental pharmacokinetic analysis was performed using the WinNonlin program. Results: The maximum plasma concentration (Cmax) of salicylic acid was 5433 and 5719 ng/mL reached in 3.66 and 4.02 h (tmax) for the test and the reference formulation, respectively. The 90% confidence interval of the ratios of geometric means of Cmax and area under curve of plasma concentration until the last concentration observed (AUC0- last) were within the interval 80-125%. Conclusion: The new acetylsalicylic acid formulation has a bioavailability equivalent to the reference formulation for the rate and the extent of absorption

INR Telemonitoring: Efficacy and Safety of a Telemonitoring Program in 453 Patients

Introdução: A análise do valor de INR em doentes hipocoagulados traz grande sobrecarga aos profissionais de saúde, despesas excessivas ao Serviço Nacional de Saúde (SNS) e perda de qualidade de vida dos doentes que se vêem obrigados a deslocações hospitalares frequentes. Não deveria constituir surpresa que a tecnologia esteja na vanguarda dos cuidados de saúde no século XXI e na área da anticoagulação têm sido desenvolvidos projectos de auto-monitorização do INR através do telefone, telemóvel ou internet. O objectivo deste estudo foi analisar a eficácia e segurança de um sistema de telemonitorização de INR implementado no nosso hospital em 2006. Material e Métodos: Estudo observacional, prospectivo dos 453 doentes incluídos no sistema de telemonitorização de INR desde 2006 até final Novembro 2010. A comunicação entre o doente e os profissionais de saúde é feita através de mensagens do telemóvel num sistema codificado e estandardizado que inclui informação sobre a manutenção ou alteração de terapêutica sempre que necessário e a data da próxima avaliação. Sempre que necessário o doente pode emitir um pedido de ajuda através de um código para o efeito. Na população estudada avaliaram-se os seguintes parâmetros: desistência do projecto de telemonitorização, necessidade de modificação da dose do anticoagulante, pedidos de esclarecimento por parte do doente, complicações hemorrágicas e internamento por INR > 10. Resultados: Da população estudada 53% eram do sexo feminino, idade média = 57 +/- 16. A percentagem dos valores de INR dentro do intervalo terapêutico obtida foi de 83%. Não se registaram desistências do projecto de telemonitorização. A percentagem de doentes com complicações hemorrágicas minor e major durante o follow-up foi de 0,4% e 0,2% respectivamente. Conclusões: O sistema de telemonitorização mostra-se seguro e eficaz no controlo à distância de análise de INR, permitindo controlo eficaz de INR com baixa prevalência de hemorragias major ou minor

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Diminished Self-Chaperoning Activity of the ΔF508 Mutant of CFTR Results in Protein Misfolding

The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and cell biological studies show that the ΔF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the ΔF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-ΔF508 variants exhibited significantly higher folding probabilities than the original NBD1-ΔF508, thereby partially rescuing folding ability of the NBD1-ΔF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of NBD1-ΔF508 are essential information in correcting this pathogenic mutant

Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay

Background: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans.Methods: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice.Results: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience.Conclusions: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy. © 2014 Weber et al.; licensee BioMed Central Ltd

Vitamin C and E Supplementation Effects in Professional Soccer Players Under Regular Training

Exercise training is known to induce an increase in free radical production potentially leading to enhanced muscle injury. Vitamins C and E are well known antioxidants that may prevent muscle cell damage. The purpose of this study was to determine the effects of these supplemental antioxidant vitamins on markers of oxidative stress, muscle damage and performance of elite soccer players. Ten male young soccer players were divided into two groups. Supplementation group (n = 5) received vitamins C and E supplementation daily during the pre-competitive season (S group), while the placebo group (PL group, n = 5) received a pill containing maltodextrin. Both groups performed the same training load during the three-month pre-season training period. Erythrocyte antioxidant enzymes glutathione reductase, catalase and plasma carbonyl derivatives did not show any significant variation among the experimental groups. Similarly, fitness level markers did not differ among the experimental groups. However, S group demonstrated lower lipid peroxidation and muscle damage levels (p < 0.05) compared to PL group at the final phase of pre-competitive season. In conclusion, our data demonstrated that vitamin C and E supplementation in soccer players may reduce lipid peroxidation and muscle damage during high intensity efforts, but did not enhance performance

Chemical diplomacy in male tilapia: urinary signal increases sex hormone and decreases aggression

Androgens, namely 11-ketotestosterone (11KT), have a central role in male fish reproductive physiology and are thought to be involved in both aggression and social signalling. Aggressive encounters occur frequently in social species, and fights may cause energy depletion, injury and loss of social status. Signalling for social dominance and fighting ability in an agonistic context can minimize these costs. Here, we test the hypothesis of a 'chemical diplomacy' mechanism through urinary signals that avoids aggression and evokes an androgen response in receiver males of Mozambique tilapia (Oreochromis mossambicus). We show a decoupling between aggression and the androgen response; males fighting their mirror image experience an unresolved interaction and a severe drop in urinary 11KT. However, if concurrently exposed to dominant male urine, aggression drops but urinary 11KT levels remain high. Furthermore, 11KT increases in males exposed to dominant male urine in the absence of a visual stimulus. The use of a urinary signal to lower aggression may be an adaptive mechanism to resolve disputes and avoid the costs of fighting. As dominance is linked to nest building and mating with females, the 11KT response of subordinate males suggests chemical eavesdropping, possibly in preparation for parasitic fertilizations.info:eu-repo/semantics/publishedVersio