Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg^?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg^?1, ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO₂ 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO₂ > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg^?1 hour^?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg^?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.     

Assessing foraging strategies of herbivores in Mediterranean oak woodlands: a review of key issues and selected methodologies

Montados are agro-silvo-pastoral ecosystems, typical of the Southwest Iberian Peninsula, of high socio-economic and conservation importance, where grazing is a dominant activity. Montados are characterized by an open tree canopy of Quercus sp. and a diverse undercover of shrubs and grasslands that constitute the plant food resources for grazing animals. Plant food resources of Montados are highly variable, both spatially and seasonally, in quantity and quality. Reliable and easy to use methods to monitor grazing are necessary to allow proper understanding of foraging strategies of grazing animals and to set sustainable grazing management. We describe the main characteristics of the plant food resources available for grazing animals, striking its variability, and revise the potential of using N-alkanes and saliva proteome methods to assess foraging strategies in Montados. In a scenario of dynamic multiple choices, we discuss the use of n-alkane methodology for the simultaneous estimation of diet composition and voluntary intake and saliva proteome as a mean of increasing the knowledge on diet adjustments.     

Predictive Factors of Sensitivity to Elisidepsin,a Novel Kahalalide F-Derived Marine Compound

Elisidepsin (PM02734, Irvalec^®) is a synthetic marine-derived cyclic peptide of the Kahalalide F family currently in phase II clinical development. Elisidepsin was shown to induce rapid oncosis in ErbB3-expressing cells. Other predictive factors of elisidepsin sensitivity remained unknown. A panel of 23 cancer cell lines of different origin was assessed for elisidepsin cytotoxicity and correlated with mutational state, mRNA and protein expression of selected genes. Elisidepsin showed potent and broad cytotoxic effects in our cancer cell line panel, being active at concentrations ranging from 0.4 to 2 μM that may be relevant for clinical settings. We have shown that elisidepsin is more active in cells harboring epithelial phenotype with high E-cadherin and low vimentin expression. In addition, high ErbB3 and Muc1 expression was correlated with sensitivity to elisidepsin, whereas the presence of KRAS activating mutations was associated with resistance. In DU-PM cells with acquired resistance to elisidepsin, ErbB3 expression was decreased, while Bcl2 was increased. DU-PM cells displayed higher sensitivity to ErbB1-inhibitors suggesting possible cross-talk of ErbB1 and ErbB3 signaling pathways. Combinations of elisidepsin with lapatinib and several chemotherapies including 5-FU and oxaliplatin resulted in synergistic effects that offer the potential of clinical use of elisidepsin in combination settings.     

Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae)

The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. The TSH fraction was the most effective against HSV-1 replication (SI = 15.33), whereas compounds 1 (SI = 2.46) and 2 (SI = 1.95) were less active. The most active fraction and these compounds were also assayed to determine the viral multiplication step(s) upon which they act as well as their potential synergistic effects. The anti-HSV-1 activity detected was mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. In summary, these results suggest that the anti-HSV-1 activity of TSH fraction detected is possibly related to the synergic effects of compounds 1 and 2.     

The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia

Background

Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA. Since the classic osmotic fragility test (COFT) is time-consuming and requires specialized equipment, an easy and less labour-intensive rapid osmotic fragility test (ROFT) has been used in some countries, but its diagnostic value has not yet been investigated.This study aimed to evaluate erythrocyte osmotic fragility in dogs with and without IMHA, to compare results of the classic (COFT) and rapid (ROFT) test and to assess the value of the ROFT as diagnostic test for canine IMHA.Nineteen dogs with IMHA (group 1a), 21 anaemic dogs without IMHA (group 1b), 8 dogs with microcytosis (group 2), 13 hyperlipemic dogs (group 3), 10 dogs with lymphoma (group 4), 8 dogs with an infection (group 5) and 13 healthy dogs (group 6) were included.In all dogs, blood smear examination, in-saline auto-agglutination test, Coombs’ test, COFT and ROFT were performed. In the COFT, OF5, OF50 and OF90 were defined as the NaCl concentrations at which respectively 5, 50 and 90% of erythrocytes were haemolysed.

Results

Compared with healthy dogs, OF5 and OF50 were significantly higher in group 1a (P < 0.001) and OF5 was significantly higher in group 3 (P = 0.0266). The ROFT was positive in 17 dogs with IMHA, 10 hyperlipemic dogs, one anaemic dog without IMHA and one healthy dog.

Conclusions

Osmotic fragility was increased in the majority of dogs with IMHA and in dogs with hyperlipidemia, but not in dogs with microcytosis, lymphoma or an infection. Although more detailed information was obtained about the osmotic fragility by using the COFT, the COFT and ROFT gave similar results. The ROFT does not require specialized equipment, is rapid and easy to perform and can be used easily in daily practice. Although, the ROFT cannot replace other diagnostic tests, it may be a valuable additional tool to diagnose canine IMHA.     

Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine

Brucella melitensis Rev 1 is the best vaccine available for the prophylaxis of small ruminant brucellosis and, indirectly, for reducing human brucellosis. However, Rev 1 shows anomalously high rates of spontaneous dissociation from smooth (S) to rough (R) bacteria, the latter being inefficacious as vaccines. This S-R instability results from the loss of the O-polysaccharide. To overcome this problem, we investigated whether some recently described mechanisms promoting mutations in O-polysaccharide genes were involved in Rev 1 S-R dissociation. We found that a proportion of Rev 1 R mutants result from genome rearrangements affecting the wbo O-polysaccharide loci of genomic island GI-2 and the wbkA O-polysaccharide glycosyltransferase gene of the wbk region. Accordingly, we mutated the GI-2 int gene and the wbk IS transposase involved in those arrangements, and found that these Rev 1 mutants maintained the S phenotype and showed lower dissociation levels. Combining these two mutations resulted in a strain (Rev 2) displaying a 95% decrease in dissociation with respect to parental Rev 1 under conditions promoting dissociation. Rev 2 did not differ from Rev 1 in the characteristics used in Rev 1 typing (growth rate, colonial size, reactivity with O-polysaccharide antibodies, phage, dye and antibiotic susceptibility). Moreover, Rev 2 and Rev 1 showed similar attenuation and afforded similar protection in the mouse model of brucellosis vaccines. We conclude that mutations targeting genes and DNA sequences involved in spontaneous O-polysaccharide loss enhance the stability of a critical vaccine phenotype and complement the empirical stabilization precautions taken during S Brucella vaccine production.     

Optimal Management Practices for Nitrogen Application in Corn Cultivated During Summer and Fall in the Tropics

Optimal management practices for nitrogen (N) fertilization is well defined for corn (Zea mays) cultivated during summer (“summer” corn), but not for corn cultivated during the fall (“fall” corn) in the tropics. Two experiments were carried out to evaluate N rates (50, 100, 200, and 300 kg N ha^?1), N application timing (pre-planting – PP, V2–V3, and V5–V6) and N split application, once (at PP, V3, and V6), two (at V3+ V6) and three times (at PP+ V3+ V6) in corn cultivated during summer (2014/2015) and fall (2015/2016). Data on corn grain yield (CGY), weight of 1000-grains, leaf N content and values of soil-plant analyses development (SPAD) were collected and analyzed using univariate, multivariate (principal component analysis, PCA) and regression analysis. Results showed that corn growth was affected by N rates and splitting. Corn cultivated during summer presented higher CGY and weight-1000 g than corn cultivated during the fall. The highest yields were obtained with higher N rates on “summer” corn (125 kg N ha^?1) than “fall” corn (50 kg N ha^?1). Split N-application at vegetative growth stages, V3+ V6, or PP+ V2+ V6, provided higher yields for “summer” corn, while only PP application was a reliable period of N fertilization for “fall” corn. The finding is that corn cultivated during the fall presented a lower response to N and no obvious advantages to split N fertilization when compared to corn cultivated during summer. These optimal management practices for N fertilization in corn production in the tropics depend on soil water availability.     

Recombinant human lactoferrin and iron transport across Caco-2 monolayers: effect of heat treatment on the binding to cells

Recombinant human lactoferrin (rhLF) from Aspergillus awamori bound to Caco-2 cell membranes in a saturable manner. The dissociation constant for the apo form was (Kd)=2.2 x 10(-7) M; however, the specific binding of the iron-saturated rhLF and of lactoferrin from human milk (hLF) was too low to calculate the binding parameters. Recombinant human lactoferrin subjected to heat treatment did not lose the ability to bind to cell membranes except at high temperature and long time treatments (85 and 89 degrees C for 40 min) for which there was a slight decrease in the binding. No significant differences have been found in the transport of iron bound to rhLF or to hLF across Caco-2 cell monolayers. Nevertheless, the amount of iron-saturated hLF transported across Caco-2 monolayers was significantly higher than that of rhLF. For both lactoferrins, the amount of intact protein in the lower chamber was about 4.5% of the total radioactivity transported, indicating the degradation of lactoferrin in the passage across Caco-2 cells.