Effect of intraperitioneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

The present study evaluated the acute effect of the intraperitoneal. (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 mu L min(-1) 100 g body weight(-1)) compared to 0.15 M NaCl-treated (890 26 mu L min(-1) 100 g body weight(-1)) and captopril-treated (903 +/- 72 mu L min(-1) 100 g body weight(-1)) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin Id levels are needed to support this suggestion.38121817182

Direct and Inverse Variational Problems on Time Scales: A Survey

We deal with direct and inverse problems of the calculus of variations on arbitrary time scales. Firstly, using the Euler-Lagrange equation and the strengthened Legendre condition, we give a general form for a variational functional to attain a local minimum at a given point of the vector space. Furthermore, we provide a necessary condition for a dynamic integro-differential equation to be an Euler-Lagrange equation (Helmholtz's problem of the calculus of variations on time scales). New and interesting results for the discrete and quantum settings are obtained as particular cases. Finally, we consider very general problems of the calculus of variations given by the composition of a certain scalar function with delta and nabla integrals of a vector valued field.Comment: This is a preprint of a paper whose final and definite form will be published in the Springer Volume 'Modeling, Dynamics, Optimization and Bioeconomics II', Edited by A. A. Pinto and D. Zilberman (Eds.), Springer Proceedings in Mathematics & Statistics. Submitted 03/Sept/2014; Accepted, after a revision, 19/Jan/201

AGUIA: autonomous graphical user interface assembly for clinical trials semantic data services

<p>Abstract</p> <p>Background</p> <p>AGUIA is a front-end web application originally developed to manage clinical, demographic and biomolecular patient data collected during clinical trials at MD Anderson Cancer Center. The diversity of methods involved in patient screening and sample processing generates a variety of data types that require a resource-oriented architecture to capture the associations between the heterogeneous data elements. AGUIA uses a semantic web formalism, resource description framework (RDF), and a bottom-up design of knowledge bases that employ the S3DB tool as the starting point for the client's interface assembly.</p> <p>Methods</p> <p>The data web service, S3DB, meets the necessary requirements of generating the RDF and of explicitly distinguishing the description of the domain from its instantiation, while allowing for continuous editing of both. Furthermore, it uses an HTTP-REST protocol, has a SPARQL endpoint, and has open source availability in the public domain, which facilitates the development and dissemination of this application. However, S3DB alone does not address the issue of representing content in a form that makes sense for domain experts.</p> <p>Results</p> <p>We identified an autonomous set of descriptors, the GBox, that provides user and domain specifications for the graphical user interface. This was achieved by identifying a formalism that makes use of an RDF schema to enable the automatic assembly of graphical user interfaces in a meaningful manner while using only resources native to the client web browser (JavaScript interpreter, document object model). We defined a generalized RDF model such that changes in the graphic descriptors are automatically and immediately (locally) reflected into the configuration of the client's interface application.</p> <p>Conclusions</p> <p>The design patterns identified for the GBox benefit from and reflect the specific requirements of interacting with data generated by clinical trials, and they contain clues for a general purpose solution to the challenge of having interfaces automatically assembled for multiple and volatile views of a domain. By coding AGUIA in JavaScript, for which all browsers include a native interpreter, a solution was found that assembles interfaces that are meaningful to the particular user, and which are also ubiquitous and lightweight, allowing the computational load to be carried by the client's machine.</p

A quantitative view of the transcriptome of Schistosoma mansoni adult-worms using SAGE

<p>Abstract</p> <p>Background</p> <p>Five species of the genus Schistosoma, a parasitic trematode flatworm, are causative agents of Schistosomiasis, a disease that is endemic in a large number of developing countries, affecting millions of patients around the world. By using SAGE (Serial Analysis of Gene Expression) we describe here the first large-scale quantitative analysis of the Schistosoma mansoni transcriptome, one of the most epidemiologically relevant species of this genus.</p> <p>Results</p> <p>After extracting mRNA from pooled male and female adult-worms, a SAGE library was constructed and sequenced, generating 68,238 tags that covered more than 6,000 genes expressed in this developmental stage. An analysis of the ordered tag-list shows the genes of F10 eggshell protein, pol-polyprotein, HSP86, 14-3-3 and a transcript yet to be identified to be the five top most abundant genes in pooled adult worms. Whereas only 8% of the 100 most abundant tags found in adult worms of S. mansoni could not be assigned to transcripts of this parasite, 46.9% of the total ditags could not be mapped, demonstrating that the 3 sequence of most of the rarest transcripts are still to be identified. Mapping of our SAGE tags to S. mansoni genes suggested the occurrence of alternative-polyadenylation in at least 13 gene transcripts. Most of these events seem to shorten the 3 UTR of the mRNAs, which may have consequences over their stability and regulation.</p> <p>Conclusion</p> <p>SAGE revealed the frequency of expression of the majority of the S. mansoni genes. Transcriptome data suggests that alternative polyadenylation is likely to be used in the control of mRNA stability in this organism. When transcriptome was compared with the proteomic data available, we observed a correlation of about 50%, suggesting that both transcriptional and post-transcriptional regulation are important for determining protein abundance in S. mansoni. The generation of SAGE tags from other life-cycle stages should contribute to reveal the dynamics of gene expression in this important parasite.</p

Dicationic Alkylammonium Bromide Gemini Surfactants. Membrane Perturbation and Skin Irritation

Dicationic alkylammonium bromide gemini surfactants represent a class of amphiphiles potentially effective as skin permeation enhancers. However, only a limited number of studies has been dedicated to the evaluation of the respective cytotoxicity, and none directed to skin irritation endpoints. Supported on a cell viability study, the cytotoxicity of gemini surfactants of variable tail and spacer length was assessed. For this purpose, keratinocyte cells from human skin (NCTC 2544 cell line), frequently used as a model for skin irritation, were employed. The impact of the different gemini surfactants on the permeability and morphology of model vesicles was additionally investigated by measuring the leakage of calcein fluorescent dye and analyzing the NMR spectra of 31P, respectively. Detail on the interaction of gemini molecules with model membranes was also provided by a systematic differential scanning calorimetry (DSC) and molecular dynamics (MD) simulation. An irreversible impact on the viability of the NCTC 2544 cell line was observed for gemini concentrations higher than 25 mM, while no cytotoxicity was found for any of the surfactants in a concentration range up to 10 mM. A higher cytotoxicity was also found for gemini surfactants presenting longer spacer and shorter tails. The same trend was obtained in the calorimetric and permeability studies, with the gemini of longest spacer promoting the highest degree of membrane destabilization. Additional structural and dynamical characterization of the various systems, obtained by 31P NMR and MD, provide some insight on the relationship between the architecture of gemini surfactants and the respective perturbation mechanism

Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

Influence of Ecto-Nucleoside Triphosphate Diphosphohydrolase Activity on Trypanosoma cruzi Infectivity and Virulence

The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, an endemic zoonosis present in some countries of South and Central Americas. The World Health Organization estimates that 100 million people are at risk of acquiring this disease. The infection affects mainly muscle tissues in the heart and digestive tract. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed, which makes a strong case for the development of new drugs to treat the disease. In this work we evaluate a family of proteins called Ecto-Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) as new chemotherapy target to block T. cruzi infection in mammalian cells and in mice. We have used inhibitors and antibodies against this protein and demonstrated that T. cruzi Ecto-NTPDases act as facilitators of infection in mammalian cells and virulence factors in mice model. Two of the drugs used in this study (Suramin and Gadolinium) are currently used for other diseases in humans, supporting the possibility of their use in the treatment of Chagas disease

High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro

Background: Dogs are commonly affected by hyperglycemic conditions. Hyperglycemia compromises the immune response and favors bacterial infections; however, reports on the effects of glucose on neutrophil oxidative metabolism and apoptosis are conflicting in humans and rare in dogs. Considering the many complex factors that affect neutrophil oxidative metabolism in vivo, we investigated in vitro the specific effect of high concentrations of glucose on superoxide production and apoptosis rate in neutrophils from healthy dogs.Results: The capacity of the neutrophils to reduce tetrazolium nitroblue decreased significantly in the higher concentration of glucose (15.13 ± 9.73% (8 mmol/L) versus 8.93 ± 5.71% (16 mmol/L)). However, there were no changes in tetrazolium nitroblue reduction at different glucose concentrations when the neutrophils were first activated with phorbol myristate acetate. High concentrations of glucose did not affect the viability and apoptosis rate of canine neutrophils either with or without prior camptothecin stimulation. This study provides the first evidence that high concentrations of glucose inhibit the oxidative metabolism of canine neutrophils in vitro in a manner similar to that which occurs in humans, and that the decrease in superoxide production did not increase the apoptosis rate.Conclusions: A high concentration of glucose reduces the oxidative metabolism of canine neutrophils in vitro. It is likely that glucose at high concentrations rapidly affects membrane receptors responsible for the activation of NADPH oxidase in neutrophils; therefore, the nonspecific immune response can be compromised in dogs with acute and chronic hyperglycemic conditions. © 2013 Bosco et al.; licensee BioMed Central Ltd

Anti-inflammatory and analgesic potential of hydrolyzed extract of Agave sisalana Perrine ex Engelm., Asparagaceae

The hemolytic, anti-inflammatory and antinociceptive properties from hydrolyzed extract Agave sisalana Perrine ex Engelm., Asparagaceae (HEAS) was evaluated classic inflammation models. Male Swiss mice and male Wistars rats received HEAS (500 mg/kg) in two administration p.o. and i.p. in saline solution 0.9%. The acid hydrolysis inhibited the hemolytic action of saponins due to the retreat of side chain sugar. The treatment of the ear induced oedema by xylene with HEAS significantly reduced in two routes 13 +/- 1.5 and 10 +/- 0.63 mg, respectively, p.o. and i.p., in comparison with controls 27 1.5 saline and 13.5 +/- 1.2 AAS. The HEAS also diminished edema induced by carrageenin 43 +/- 1.58 mg (p.o.) and 17 +/- 1.26 mg (i.p.), when compared with control groups 52 +/- 1.58 mg (saline) and 10.05 +/- 1.58 (indomethacin). HEAS showed analgesic effects in abdominal constrictions 30.7% (p.o.), 88.7% (i.p.) comparable to that produced by (AAS) 70.6%. However in granuloma cotton pellet a chronic model of inflammation just the i.p. pathway decreased granulomatous tissue (20.4 +/- 1.32 mg) compared with controls 30.5 +/- 2.53 mg (saline) and 20.2 +/- 2.18 mg (dexamethasone). These data suggest that HEAS has anti-inflammatory and analgesic activity on acute and chronic processes.20337638