Pharmacokinetics and pharmacodynamics of the glucagon-like peptide-1 analog liraglutide in healthy cats

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that induces glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Glucagon-like peptide-1 also increases beta cell mass and satiation while decelerating gastric emptying. Liraglutide is a fatty-acid derivative of GLP-1 with a protracted pharmacokinetic profile that is used in people for treatment of type II diabetes mellitus and obesity. The aim of this study was to determine the pharmacokinetics and pharmacodynamics of liraglutide in healthy cats. Hyperglycemic clamps were performed on days 0 (HGC) and 14 (LgHGC) in 7 healthy cats. Liraglutide was administered subcutaneously (0.6 mg/cat) once daily on days 8 through 14. Compared with the HGC (mean +/- standard deviation; 455.5 +/- 115.8 ng/L), insulin concentrations during LgHGC were increased (760.8 +/- 350.7 ng/L; P = 0.0022), glucagon concentrations decreased (0.66 +/- 0.4 pmol/L during HGC vs 0.5 +/- 0.4 pmol/L during LgHGC; P = 0.0089), and there was a trend toward an increased total glucose infused (median [range] = 1.61 (1.11-2.54) g/kg and 2.25 (1.64-3.10) g/kg, respectively; P = 0.087). Appetite reduction and decreased body weight (9% +/- 3%; P = 0.006) were observed in all cats. Liraglutide has similar effects and pharmacokinetics profile in cats to those reported in people. With a half-life of approximately 12 h, once daily dosing might be feasible; however, significant effects on appetite and weight loss may necessitate dosage or dosing frequency reductions. Further investigation of liraglutide in diabetic cats and overweight cats is warranted. (C) 2015 Elsevier Inc. All rights reserved.

Local order and magnetic field effects on the electronic properties of disordered binary alloys in the quantum site percolation limit

Electronic properties of disordered binary alloys are studied via the calculation of the average Density of States (DOS) in two and three dimensions. We propose a new approximate scheme that allows for the inclusion of local order effects in finite geometries and extrapolates the behavior of infinite systems following finite-size scaling ideas. We particularly investigate the limit of the Quantum Site Percolation regime described by a tight-binding Hamiltonian. This limit was chosen to probe the role of short range order (SRO) properties under extreme conditions. The method is numerically highly efficient and asymptotically exact in important limits, predicting the correct DOS structure as a function of the SRO parameters. Magnetic field effects can also be included in our model to study the interplay of local order and the shifted quantum interference driven by the field. The average DOS is highly sensitive to changes in the SRO properties and striking effects are observed when a magnetic field is applied near the segregated regime. The new effects observed are twofold: there is a reduction of the band width and the formation of a gap in the middle of the band, both as a consequence of destructive interference of electronic paths and the loss of coherence for particular values of the magnetic field. The above phenomena are periodic in the magnetic flux. For other limits that imply strong localization, the magnetic field produces minor changes in the structure of the average DOS. © World Scientific Publishing Company.

Hilbert space of curved βγ systems on quadric cones

We clarify the structure of the Hilbert space of curved βγ systems defined by a quadratic constraint. The constraint is studied using intrinsic and BRST methods, and their partition functions are shown to agree. The quantum BRST cohomology is non-empty only at ghost numbers 0 and 1, and there is a one-to-one mapping between these two sectors. In the intrinsic description, the ghost number 1 operators correspond to the ones that are not globally defined on the constrained surface. Extension of the results to the pure spinor superstring is discussed in a separate work.

Geoffroy's side-necked turtle [Phrynops geoffroanus (Schweigger, 1812), Testudines: Chelidae] as a model for evolutionary ecotoxicology: relationship between environmental contamination, conditions and genetic variability

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Is the internal connection more efficient than external connection in mechanical, biological, and esthetical point of views? A systematic review

This systematic review aimed to evaluate if the internal connection is more efficient than the external connection and its associated influencing factors. A specific question was formulated according to the Population, Intervention, Control, and Outcome (PICO): Is internal connection more efficient than external connection in mechanical, biological, and esthetical point of views? An electronic search of the MEDLINE and the Web of Knowledge databases was performed for relevant studies published in English up to November 2013 by two independent reviewers. The keywords used in the search included a combination of dental implant and internal connection or Morse connection or external connection. Selected studies were randomized clinical trials, prospective or retrospective studies, and in vitro studies with a clear aim of investigating the internal and/or external implant connection use. From an initial screening yield of 674 articles, 64 potentially relevant articles were selected after an evaluation of their titles and abstracts. Full texts of these articles were obtained with 29 articles fulfilling the inclusion criteria. Morse taper connection has the best sealing ability. Concerning crestal bone loss, internal connections presented better results than external connections. The limitation of the present study was the absence of randomized clinical trials that investigated if the internal connection was more efficient than the external connection. The external and internal connections have different mechanical, biological, and esthetical characteristics. Besides all systems that show proper success rates and effectiveness, crestal bone level maintenance is more important around internal connections than external connections. The Morse taper connection seems to be more efficient concerning biological aspects, allowing lower bacterial leakage and bone loss in single implants, including aesthetic regions. Additionally, this connection type can be successfully indicated for fixed partial prostheses and overdenture planning, since it exhibits high mechanical stability.

Solving the multiobjective environmental/economic dispatch problem using weighted sum and ε-constraint strategies and a predictor-corrector primal-dual interior point method

This paper proposes a technique for solving the multiobjective environmental/economic dispatch problem using the weighted sum and ε-constraint strategies, which transform the problem into a set of single-objective problems. In the first strategy, the objective function is a weighted sum of the environmental and economic objective functions. The second strategy considers one of the objective functions: in this case, the environmental function, as a problem constraint, bounded above by a constant. A specific predictor-corrector primal-dual interior point method which uses the modified log barrier is proposed for solving the set of single-objective problems generated by such strategies. The purpose of the modified barrier approach is to solve the problem with relaxation of its original feasible region, enabling the method to be initialized with unfeasible points. The tests involving the proposed solution technique indicate i) the efficiency of the proposed method with respect to the initialization with unfeasible points, and ii) its ability to find a set of efficient solutions for the multiobjective environmental/economic dispatch problem.

Integration of R&D and new product development: case studies of Brazilian high-tech firms

One of the aspects that influence good performance of new product development (NPD) at high-tech companies is the integration of research and development (R&D) and the other functions involved with NPD. The objective of this paper is to examine why Brazilian medium and large sized high-tech companies are different with respect to the integration of R&D with NPD. An analysis of case studies was conducted at five Brazilian high-tech firms. Among the results, collectivism, which is characteristic of the Brazilian organisational culture, was seen to manifest itself in companies through the adoption of cross-functional teams; the valorisation of personal relations, which is stimulated by physical proximity; and project managers’ ample participation in different functions involving NPD.

Influence of the starting time of preslaughter feed withdrawal on welfare of pigs and pork quality

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mineral element and heavy metal poisoning in animals

Mineral elements are essential to animal health, survival and production because they are part of physiological, structural, catalytic and regulatory organism functions. Therefore, they should be present in diet. However, these minerals when ingested in excessive doses due to errors in balancing mineral supplements and/or complete ration, intake of plants with high mineral concentration, resulting from addition of fertilizers, herbicides, insecticides and fungicides in pasture or tillage where plants and/or grains will be used to feed animals, decomposition of urban and industrial wastes, leaks and accidental spills of pollutants may result in accumulation of toxic mineral elements in the environment poisoning the animals and may lead them to death. However, toxic doses, physiological changes during poisoning, symptoms and mineral concentration in tissues of poisoned animals to confirm diagnosis are not completely known. Thus, this study reviews mineral element doses that some authors considered toxic for animals intake, as its concentration in tissues of poisoned animals and its physiological effects, symptoms, diagnostic procedures and treatment for poisoning by cadmium, lead, copper, chromium, iodine, manganese, molybdenum, selenium and zinc.

Influence of sanitization on the physico-chemical and microbiological quality of organic and conventional broccoli

The present study was carried out in order to evaluate the effect of chlorinated and ozonized water on the physico-chemical characteristics of broccoli, produced under organic and conventional cultivation procedures. Organic and conventional broccolis were subjected to two sanitation treatments, using chlorine and ozone, and were kept under cold storage for seven days. Analyses of pH, titrable acidity, soluble solids and weight loss were performed and the content of Cu, Mn and Zn was determined. In addition, the presence of pesticides was verified. The results show no influence of the cultivation method or the sanitation treatment on sample weight loss. Cultivation methods and sanitizing treatments affected broccoli pH, titratable acidity, and soluble solids during the evaluation period. No differences regarding the metal content on organic and conventional broccoli were observed. Furthermore, the presence of organochlorine compounds, nor other pesticides, was not detected both in organic and conventional vegetables.

Relationship between sweet orange yield and intensity of Citrus Variegated Chlorosis

Citrus Variegated Chlorosis (CVC) is currently present in approximately 40% of citrus plants in Brazil and causes an annual loss of around 120 million US dollars to the Brazilian citrus industry. Despite the fact that CVC has been present in Brazil for over 20 years, a relationship between disease intensity and yield loss has not been established. In order to achieve this, an experiment was carried out in a randomized block design in a 3 x 2 factorial scheme with 10-year-old Natal sweet orange. The following treatments were applied: irrigation with 0, 50 or 100% of the evapotranspiration of the crop, combined with natural infection or artificial inoculation with Xylella fastidiosa, the causal agent of CVC. The experiment was evaluated during three seasons. A negative exponential model was fitted to the relationships between yield versus CVC severity and yield versus Area Under Disease Progress Curve (AUDPC). In addition, the relationship between yield versus CVC severity and canopy volume was fitted by a multivariate exponential model. The use of the AUDPC variable showed practical limitations when compared with the variable CVC severity. The parameter values in the relationship of yieldCVC severity were similar for all treatments unlike in the multivariate model. Consequently, the yieldCVC intensity relationship (with 432 data points) could be described by one single model: y = 114.07 exp(-0.017 x), where y is yield (symptomless fruit weight in kg) and x is disease severity (R2 = 0.45; P < 0.01).

Natural intracellular peptides can modulate the interactions of mouse brain proteins and thimet oligopeptidase with 14-3-3e and calmodulin

Protein interactions are crucial for most cellular process. Thus, rationally designed peptides that act as competitive assembly inhibitors of protein interactions by mimicking specific, determined structural elements have been extensively used in clinical and basic research. Recently, mammalian cells have been shown to contain a large number of intracellular peptides of unknown function. Here, we investigate the role of several of these natural intracellular peptides as putative modulators of protein interactions that are related to Ca2+-calmodulin (CaM) and 14-3-3 epsilon, which are proteins that are related to the spatial organization of signal transduction within cells. At concentrations of 1-50 mu M, most of the peptides that are investigated in this study modulate the interactions of CaM and 14-3-3 epsilon with proteins from the mouse brain cytoplasm or recombinant thimet oligopeptidase (EP24.15) in vitro, as measured by surface plasmon resonance. One of these peptides (VFDVELL; VFD-7) increases the cytosolic Ca2+ concentration in a dose-dependent manner but only if introduced into HEK293 cells, which suggests a wide biological function of this peptide. Therefore, it is exciting to suggest that natural intracellular peptides are novel modulators of protein interactions and have biological functions within cells.

Additional scaled solutions to Richards' equation for infiltration and drainage

Warrick and Hussen developed in the nineties of the last century a method to scale Richards' equation (RE) for similar soils. In this paper, new scaled solutions are added to the method of Warrick and Hussen considering a wider range of soils regardless of their dissimilarity. Gardner-Kozeny hydraulic functions are adopted instead of Brooks-Corey functions used originally by Warrick and Hussen. These functions allow to reduce the dependence of the scaled RE on the soil properties. To evaluate the proposed method (PM), the scaled RE was solved numerically using a finite difference method with a fully implicit scheme. Three cases were considered: constant-head infiltration, constant-flux infiltration, and drainage of an initially uniform wet soil. The results for five texturally different soils ranging from sand to clay (adopted from the literature) showed that the scaled solutions were invariant to a satisfactory degree. However, slight deviations were observed mainly for the sandy soil. Moreover, the scaled solutions deviated when the soil profile was initially wet in the infiltration case or when deeply wet in the drainage condition. Based on the PM, a Philip-type model was also developed to approximate RE solutions for the constant-head infiltration. The model showed a good agreement with the scaled RE for the same range of soils and conditions, however only for Gardner-Kozeny soils. Such a procedure reduces numerical calculations and provides additional opportunities for solving the highly nonlinear RE for unsaturated water flow in soils. (C) 2011 Elsevier B.V. All rights reserved.

Mapping of risk and susceptibility of shallow-landslide in the city of Sao Paulo, Brazil

In the city of Sao Paulo, where about 11 million people live, landslides and flooding occur frequently, especially during the summer. These landslides cause the destruction of houses and urban equipment, economic damage, and the loss of lives. The number of areas threatened by landslides has been increasing each year. The objective of this article is to analyze the probability of risk and susceptibility to shallow landslides in the Limoeiro River basin, which is located at the head of the Aricanduva River basin, one of the main hydrographic basins in the city of Sao Paulo. To map areas of risk, we created a cadastral survey form to evaluate landslide risk in the field. Risk was categorized into four levels based on natural and anthropogenic factors: R1 (low risk), R2 (average risk), R3 (high risk), and R4 (very high risk). To analyze susceptibility to shallow landslides, we used the SHALSTAB (Shallow Landsliding Stability) mathematical model and calculated the Distribution Frequency (DF) of the susceptibility classes for the entire basin. Finally, we performed a joint analysis of the average Risk Concentration (RC) and Risk Potential (RP). We mapped 14 risk sectors containing approximately 685 at-risk homes, more than half of which presented a high (R3) or very high (R4) probability of risk to the population. In the susceptibility map, 41% of the area was classified as stable and 20% as unconditionally unstable. Although the latter category accounted a smaller proportion of the total area, it contained a concentration (RC) of 41% of the mapped risk areas with a risk potential (RP) of 12%. We found that the locations of areas predicted to be unstable by the model coincided with the risk areas mapped in the field. This combination of methods can be applied to evaluate the risk of shallow landslides in densely populated areas and can assist public managers in defining areas that are unstable and inappropriate for occupation. (C) 2012 Elsevier B.V. All rights reserved.