Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries

<p>Abstract</p> <p>Background</p> <p>Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis.</p> <p>Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A₂(PLA₂). Pancreatitis was induced by administration of TAU or PLA₂from <it>Naja mocambique mocambique </it>into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC₅₀) and maximal responses (E_MAX) were determined. Blood samples were collected for biochemical analysis.</p> <p>Results</p> <p>In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA₂(about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC₅₀nor E_MAXvalues for Ach were altered in pulmonary rings in any group. Similarly, the pEC₅₀and the E_MAXvalues for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the E_MAXfor PHE. The nitrite/nitrate (NO_x^-) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA₂protocol, respectively.</p> <p>Conclusion</p> <p>Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NO_x^-levels as consequence of intense inflammatory responses. Furthermore, the subsensitivity of contractile response to PHE in both mesenteric and pulmonary rings might be due to the complications of this pathological condition in the early stage of pancreatitis.</p

EXPRESSION IN ESCHERICHIA-COLI OF A DOMINANT IMMUNOGEN OF TRYPANOSOMA-CRUZI RECOGNIZED BY HUMAN CHAGASIC SERA

28351952

Improved care of acute exacerbation of chronic obstructive pulmonary disease in two academic emergency departments

Background: Although several chronic obstructive pulmonary disease (COPD) practice guidelines have been published, there is sparse data on the actual emergency department (ED) management of acute exacerbation of COPD (AECOPD). Aims: Our objectives were to examine concordance of ED care of AECOPD in older patients with guideline recommendations and to evaluate whether concordance has improved over time in two academic EDs. Methods: Data were obtained from two cohort studies on AECOPD performed in two academic EDs during two different time periods, 2000 and 2005–2006. Both studies included ED patients, aged 55 and older, who presented with AECOPD, and cases were confirmed by emergency physicians. Data on ED management and disposition were obtained from chart review for both cohorts. Results: The analysis included 272 patients: 72 in the 2000 database and 200 in the 2005–2006 database. The mean age of the patients was 72 years; 50% were women and 80% white. In 2005–2006, overall concordance with guideline recommendations was high (for chest radiography, pulse oximetry, bronchodilators, all ≥ 90%), except for arterial blood gas testing (7% among the admitted) and discharge medication with systemic corticosteroids (42%). Compared to the 2000 data, the use of systemic corticosteroids in the ED improved from 53 to 77% [absolute improvement: 24%, 95% confidence interval (CI): 11–37%], and the use of antibiotics among the patients with respiratory infection symptoms improved from 56 to 78% (absolute improvement: 22%, 95% CI: 6–38%). Conclusions: Overall concordance with guideline-recommended care for AECOPD was high in two academic EDs, and some emergency treatments have improved over time

Correlating structural dynamics and catalytic activity of AgAu nanoparticles with ultrafast spectroscopy and all-atom molecular dynamics simulations

In this study, we investigated hollow AgAu nanoparticles with the goal of improving our understanding of the compositiondependent catalytic activity of theses nanoparticles. AgAu nanoparticles were synthesized via the galvanic replacement method with controlled size and nanoparticle compositions. We studied extinction spectra with UV-Vis spectroscopy and simulations based on Mie theory and the boundary element method, and ultrafast spectroscopy measurements to characterize decay constants and the overall energy transfer dynamics as a function of AgAu composition. Electronphonon coupling times for each composition were obtained from pump-power dependent pump-probe transients. These spectroscopic studies showed how nanoscale surface segregation, hollow interiors and porosity affect the surface plasmon resonance wavelength and fundamental electron-phonon coupling times. Analysis of the spectroscopic data was used to correlate electron-phonon coupling times to AgAu composition, and thus to surface segregation and catalytic activity. We have performed all-atom molecular dynamics simulations of model hollow AgAu core-shell nanoparticles to characterize nanoparticle stability and equilibrium structures, besides providing atomic level views of nanoparticle surface segregation. Overall, the basic atomistic and electron-lattice dynamics of core-shell AgAu nanoparticles characterized here thus aid the mechanistic understanding and performance optimization of AgAu nanoparticle catalysts

Scoping review on vector-borne diseases in urban areas : transmission dynamics, vectorial capacity and co-infection

BACKGROUND: Transmission dynamics, vectorial capacity, and co-infections have substantial impacts on vector-borne diseases (VBDs) affecting urban and suburban populations. Reviewing key factors can provide insight into priority research areas and offer suggestions for potential interventions. MAIN BODY: Through a scoping review, we identify knowledge gaps on transmission dynamics, vectorial capacity, and co-infections regarding VBDs in urban areas. Peer-reviewed and grey literature published between 2000 and 2016 was searched. We screened abstracts and full texts to select studies. Using an extraction grid, we retrieved general data, results, lessons learned and recommendations, future research avenues, and practice implications. We classified studies by VBD and country/continent and identified relevant knowledge gaps. Of 773 articles selected for full-text screening, 50 were included in the review: 23 based on research in the Americas, 15 in Asia, 10 in Africa, and one each in Europe and Australia. The largest body of evidence concerning VBD epidemiology in urban areas concerned dengue and malaria. Other arboviruses covered included chikungunya and West Nile virus, other parasitic diseases such as leishmaniasis and trypanosomiasis, and bacterial rickettsiosis and plague. Most articles retrieved in our review combined transmission dynamics and vectorial capacity; only two combined transmission dynamics and co-infection. The review identified significant knowledge gaps on the role of asymptomatic individuals, the effects of co-infection and other host factors, and the impacts of climatic, environmental, and socioeconomic factors on VBD transmission in urban areas. Limitations included the trade-off from narrowing the search strategy (missing out on classical modelling studies), a lack of studies on co-infections, most studies being only descriptive, and few offering concrete public health recommendations. More research is needed on transmission risk in homes and workplaces, given increasingly dynamic and mobile populations. The lack of studies on co-infection hampers monitoring of infections transmitted by the same vector. CONCLUSIONS: Strengthening VBD surveillance and control, particularly in asymptomatic cases and mobile populations, as well as using early warning tools to predict increasing transmission, were key strategies identified for public health policy and practice

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi