Pharmacokinetic Study of Nobiletin and Tangeretin in Rat Serum by High-Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry

Nobiletin (NOB) and tangeretin (TAN), two of the main polymethoxylated flavones (PMFs) in citrus, influence a number of key biological pathways in mammalian cells. Although the impacts of NOB and TAN on glucose homeostasis and cholesterol regulation have been investigated in human clinical trials, much information is still lacking about the metabolism and oral bioavailability of these compounds in animals. In this study, NOB and TAN were administered to rats by gavage and intraperitoneal (ip) injection, and the blood serum concentrations of these compounds and their main metabolites were monitored by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). In addition to the administered compounds, two metabolites of TAN and eight metabolites of NOB were detected and measured over 24 h. With identical oral doses, nearly 10-fold higher absorption of NOB occurred compared to TAN. For both compounds, maximum levels of glucuronidated metabolites occurred in the blood serum at later time points (similar to 5-8 h) compared to the earlier T(max) a values for NOB and TAN. In most cases the glucuronides occurred at substantially higher concentrations than the aglycone metabolites. Low levels of NOB and TAN and their metabolites were detectable in rat blood serum even at 24 h after treatment.

NO EVIDENCE of PATHOLOGICAL AUTOIMMUNITY FOLLOWING MYCOBACTERIUM LEPRAE HEAT-SHOCK PROTEIN 65-DNA VACCINATION IN MICE

Heat-shock proteins (HSPs) are currently one of the most promising targets for the development of immunotherapy against tumours and autoimmune disorders. This protein family has the capacity to activate or modulate the function of different immune system cells. They induce the activation of monocytes, macrophages and dendritic cells, and contribute to cross-priming, an important mechanism of presentation of exogenous antigen in the context of MHC class I molecules, These various immunological properties of HSP have encouraged their use in several clinical trials. Nevertheless, an important issue regarding these proteins is whether the high homology among HSPs across different species may trigger the breakdown of immune tolerance and induce autoimmune diseases. We have developed a DNA vaccine codifying the Mycobacterium leprae Hsp65 (DNAhsp65), which showed to be highly immunogenic and protective against experimental tuberculosis. Here, we address the question of whether DNAhsp65 immunization could induce pathological autoimmunity in mice. Our results show that DNAhsp65 vaccination induced antibodies that can recognize the human Hsp60 but did not induce harmful effects in 16 different organs analysed by histopathology up to 210 days after vaccination. We also showed that anti-DNA antibodies were not elicited after DNA vaccination. The results are important for the development of both HSP and DNA-based immunomodulatory agents.

Testes size in leptodactylid frogs and occurrence of multimale spawning in the genus Leptodactylus in Brazil

Although rare, some anurans show multimale spawning. Herein we present data on testes mass relative to body mass for 11 leptodactylids and report multimale spawning in Leptodactylus chaquensis and Leptodactylus podicipinus. Testes mass averaged 4.13% of body mass for L. chaquensis and 0.75% for L. podicipinus. Testes size of both leptodactylid species with multimale spawning show that they are large and close to values recorded for rhacophorid frogs with multimale breeding (0.71-7.79%). Large testes size in frogs with multimale spawning supports the sperm competition hypothesis.

Reproductive biology of an endemic Physalaemus of the Brazilian Atlantic forest, and the trade-of between clutch and egg size in terrestrial breeders of the P. signifer group

Physalaemus crombiei is a small foam-nesting frog endemic to the Atlantic forest. It is a member of the P. signifer group known only from its type locality in Santa Teresa, State of Espírito Santo, and from another locality in the State of Bahia, Brazil. Most Physalaemus species are aquatic breeders, and species in the P. signifer group are the only ones exhibiting a tendency toward terrestrial reproduction in the genus. Here we describe the reproductive period, breeding site and reproductive modes of P. crombiei from a third population in the Atlantic forest, southeastern Brazil. We also investigated reproductive effort and size-fecundity relationships in females. Reproductive traits were compared to other species in the genus Physalaemus, especially those included in the P. signifer group. Physalaemus crombiei is a prolonged breeder, reproducing throughout the year with a peak of activity during the most rainy months (October-March). Males called from the humid forest foor and eggs embedded in foam nests were deposited in the water as well as on the humid foor amidst the leaf litter, or inside fallen leaves or tree holes containing rainwater on the forest foor. As expected, P. crombiei exhibited three alternative reproductive modes, as described for other species of the P. signifer group. The number of eggs produced per female varied from 91 to 250. Female body size is positively correlated both with ovary mass and clutch size (number of eggs per clutch). Variation in the number and size of eggs observed in Physalaemus species may be explained not only by female size, but also by the terrestrial reproductive mode exhibited by the species in the P. signifer group.

Reduction of the memory size in the microprogrammed controllers

In the paper the method of reduction of the memory size in the microprogrammed controllers with sharing codes is discussed. The idea is based on the modification of internal modules and connections of the device. Next, the reduction of the microinstruction length based on the hypergraph theory is performed, thus the total size of the memory is highly reduced. © 2011 IEEE.

Identification of Candida species in the clinical laboratory: A review of conventional, commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so-called non-albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time-consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species. © 2013 John Wiley & Sons A/S.

Use of platelet-rich plasma in the treatment of deep corneal ulcers induced in rabbits.clinical and histomorphometric evaluation

The repair process induced corneal ulcer in rabbits using platelet-rich plasma in the form of eyedrop or clot was clinically evaluated and compared. Sixty rabbits were divided into four groups of 15 animals, denominated platelet group (PG), clot group (CLG), control group (CG), and amniotic control group (AG). Experimental groups were then subdivided into three groups (M4, M7, M30), corresponding to the end of the evaluation period. There were no differences between treatments regarding ocular sensitivity, chemosis and ocular secretion. The groups treated with PRP either as eyedrop or a clot showed less opacity than the animals treated only with amniotic membrane at the moment of the final evaluation. The presence of corneal ulcers in the groups treated with PRP showed lower intensity than the other groups. Histomorphometric examination showed that corneal epithelization in the initial phase of the lesion was greater when using PRP. The use of amniotic membrane promoted corneal epithelial and stromal thickness, as well as synergism when associated to PRP.

Inbreeding, Average Relatedness Coefficient and Effective Population Size In Jaffarabadi Buffaloes Raised In Brazil

The major aim of this study was to evaluate the inbreeding (F), average relatedness coefficient (AR) and effective population size (Ne) in the Jaffarabadi buffalo breed from Brazil. Pedigree information of 1,272 animals born from 1966 was used. The effective population size was calculated in two ways: first, computed via individual increase in inbreeding and second estimated by individual increase in coancestry. The known generation numbers were 1.24, 1.76 and 2.64 for complete, equivalent and maximum generation, respectively. The effective size computed via individual increase in coancestry was small with a value of 10.82 +/- 1.29. The effective size computed by individual increase in inbreeding (10.40 +/- 3.69) was very similar but a little smaller than the previous reported value. The average values of F and AR for the population reference (1,059) were 4.22 and 12.5 percent. The mean of F for inbred animals (319) was 14.0%. The F and AR means were 5.7 and 13.3% for animals with at least 1.5 known equivalent generation and 9.3 and 15.97% for individuals having at least 2.5 equivalent generations known. It was found 78 matings between half sibs (6.14%) and 67 matings (5.27%) between parent-offspring. The estimated inbreeding increase per generation by considering maximum generation, complete generation and equivalent generation were 1.21%, 5.18% and 3.57%, respectively. Considering the uncompleted pedigree, the estimated inbreeding for the reference population could be underestimated.

Positioning and number of nutritional levels in dose-response trials to estimate the optimal-level and the adjustment of the models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Drivers of clutch-size in Fork-tailed Flycatchers (Tyrannus savana) at temperate and tropical latitudes in South America

Many species of birds exhibit a latitudinal gradient in annual reproductive investment, laying more eggs and producing more nestlings at higher latitudes. However, few studies have evaluated the mechanisms that underlie such patterns and such differences in grassland birds specifically. We monitored nests of Fork-tailed Flycatchers (Tyrannus savana) over two breeding seasons at a tropical site in Bolivia (in 2010-11 and 2011-12) and three breeding seasons at a southern temperate site in Argentina (2010-11, 2011-12 and 2012-13), testing two hypotheses explaining variation in clutch-size among populations: the food-limitation hypothesis and the nest-predation hypothesis. Mean clutch-size and mean brood-size were significantly larger at the temperate study site than at the tropical site. Availability of arthropod food per individual bird was significantly higher at the temperate site. There was no relationship, positive or negative, between rates of nest predation and either clutch- or brood-size, and thus no support for the nest-predation hypothesis. We conclude that food availability explains much of the latitudinal variation in clutch-size in this species. We discuss avenues for future research on the mechanisms underlying geographical variation in the life histories of Neotropical birds.

Natural enemies depend on remnant habitat size in agricultural landscapes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Voice disorders in teachers: clinical, videolaryngoscopical, and vocal aspects

Dysphonia is more prevalent in teachers than among the general population. The objective of this study was to analyze clinical, vocal, and videolaryngoscopical aspects in dysphonic teachers. Ninety dysphonic teachers were inquired about their voice, comorbidities, and work conditions. They underwent vocal auditory-perceptual evaluation (maximum phonation time and GRBASI scale), acoustic voice analysis, and videolaryngoscopy. The results were compared with a control group consisting of 90 dysphonic nonteachers, of similar gender and ages, and with professional activities excluding teaching and singing. In both groups, there were 85 women and five men (age range 31-50 years). In the controls, the majority of subjects worked in domestic activities, whereas the majority of teachers worked in primary (42.8%) and secondary school (37.7%). Teachers and controls reported, respectively: vocal abuse (76.7%; 37.8%), weekly hours of work between 21 and 40 years (72.2%; 80%), under 10 years of practice (36%; 23%), absenteeism (23%; 0%), sinonasal (66%; 20%) and gastroesophageal symptoms (44%; 22%), hoarseness (82%; 78%), throat clearing (70%; 62%), and phonatory effort (72%; 52%). In both groups, there were decreased values of maximum phonation time, impairment of the G parameter in the GRBASI scale (82%), decrease of F0 and increase of the rest of acoustic parameters. Nodules and laryngopharyngeal reflux were predominant in teachers; laryngopharyngeal reflux, polyps, and sulcus vocalis predominated in the controls. Vocal symptoms, comorbidities, and absenteeism were predominant among teachers. The vocal analyses were similar in both groups. Nodules and laryngopharyngeal reflux were predominant among teachers, whereas polyps, laryngopharyngeal reflux, and sulcus were predominant among controls.

Can the `yin and yang` BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry?

Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. Besides the initial positive clinical results; the effects of rTMS are stilt mixed. Therefore new toots to assess the effects of plasticity non-invasively might be useful to predict its therapeutic effects and design novel therapeutic approaches using rTMS. In this paper we propose that brain-derived neurotrophic factor (BDNF) might be such a tool. Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the `yin and yang` BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS. (C) 2008 Elsevier Ltd. All rights reserved.