Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room. For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief

Impact of alternative solid state forms and specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletability

YesIn order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity, and specific surface area of single-component, convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures. Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs) may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs, carriers, or binders due to their good compactibility performanceSolid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under Grant No. 07/SRC/B1158

Retrieval of vegetative fluid resistance terms for rigid stems using airborne lidar.

Hydraulic resistance of riparian forests is an unknown but important term in flood conveyance modeling. Lidar has proven to be a very important new data source to physically characterize floodplain vegetation. This research outlines a recent campaign that aims to retrieve vegetation fluid resistance terms from airborne laser scanning to parameterize trunk roughness. Information on crown characteristics and vegetation spacing can be extracted for individual trees to aid in the determining of trunk stem morphology. Airborne lidar data were used to explore the potential to characterize some of the prominent tree morphometric properties from natural and planted riparian poplar zones such as tree position, tree height, trunk location, and tree spacing. Allometric equations of tree characteristics extrapolated from ground measurements were used to infer below-canopy morphometric variables. Results are presented from six riparian-forested zones on the Garonne and Allier rivers in southern and central France. The tree detection and crown segmentation (TDCS) method identified individual trees with 85% accuracy, and the TreeVaW method detected trees with 83% accuracy. Tree heights were overall estimated at both river locations with an RMSE error of around 19% for both methods, but crown diameter at the six sites produced large deviations from ground-measured values of above 40% for both methods. Total height-derived trunk diameters using the TDCS method produced the closest roughness coefficient values to the ground-derived roughness coefficients. The stem roughness values produced from this method fell within guideline values

Different methodologies for calculating crown volume of Platanus hispanica trees by terrestial laser scanner and comparison with classical dendrometric measurements

Terrestrial laser scanners (TLSs) are used in forestry and fruit culture applications to perform a threedimensional geometrical characterization of trees and so make it easier to develop management systems based on that information. In addition, this data can improve the accuracy of dendrometric variable estimations, such as crown volume, obtained by standard methods. The main objective of this paper is to compare classical methods for crown volume estimation with the volumes obtained from the processing of point clouds obtained using a terrestrial laser scanner (TLS) on urban Platanus hispanica trees. This will allow faster quantification of residual biomass from pruning and therefore an improved management in future. The methods applied using TLS data were also evaluated in terms of processing speed. A set of 30 specimens were selected and their main dendrometric parameters (such as diameter breast height, crown diameter, total height, and distance from the crown base to the soil) were manually measured using classical methods. From these dendrometric parameters, the apparent crown volumes were calculated using three geometric models: cone, hemisphere, and paraboloid. Simultaneously, these trees were scanned with a Leica ScanStation2. A laser point cloud was registered for each tree and processed to obtain the crown volumes. Four processing methods were analyzed: (a) convex hull (an irregular polyhedral surface formed by triangles that surround the crown) applied to the whole point cloud that forms the crown; (b) convex hull using slices of 10 cm in height from the top to the base of the crown; (c) XY triangulation in horizontal sections; and (d) voxel discretization. All the obtained volumes (derived from classical methods and TLS) were assessed and compared. The regression equations that compare the volumes obtained by dendrometry and those derived from TLS data showed coefficients of determination (R2) greater than 0.78. The highest R2 (0.89) was obtained in the comparison between the volume calculated using a paraboloid and flat sections, which was also the fastest method. These results show the potential of TLS for predicting the crown volumes of urban trees, such as P. hispanica, to help improve their management, especially the quantification of residual biomass.The authors appreciate the financial support provided by the Spanish Ministry of Science and Innovation in the framework of the Project AGL2010-15334 and by the Generalitat Valenciana in the framework of the Project GV/2012/003.Fernández-Sarría, A.; Martínez, L.; Velázquez Martí, B.; Sajdak, M.; Estornell Cremades, J.; Recio Recio, JA. (2013). Different methodologies for calculating crown volume of Platanus hispanica trees by terrestial laser scanner and comparison with classical dendrometric measurements. Computers and Electronics in Agriculture. 90(1):176-185. https://doi.org/10.1016/j.compag.2012.09.017S17618590

Investigation of the key chemical structures involved in the anticancer activity of disulfiram in A549 non-small cell lung cancer cell line

© 2018 The Author(s). Background: Disulfiram (DS), an antialcoholism medicine, demonstrated strong anticancer activity in the laboratory but did not show promising results in clinical trials. The anticancer activity of DS is copper dependent. The reaction of DS and copper generates reactive oxygen species (ROS). After oral administration in the clinic, DS is enriched and quickly metabolised in the liver. The associated change of chemical structure may make the metabolites of DS lose its copper-chelating ability and disable their anticancer activity. The anticancer chemical structure of DS is still largely unknown. Elucidation of the relationship between the key chemical structure of DS and its anticancer activity will enable us to modify DS and speed its translation into cancer therapeutics. Methods: The cytotoxicity, extracellular ROS activity, apoptotic effect of DS, DDC and their analogues on cancer cells and cancer stem cells were examined in vitro by MTT assay, western blot, extracellular ROS assay and sphere-reforming assay. Results: Intact thiol groups are essential for the in vitro cytotoxicity of DS. S-methylated diethyldithiocarbamate (S-Me-DDC), one of the major metabolites of DS in liver, completely lost its in vitro anticancer activity. In vitro cytotoxicity of DS was also abolished when its thiuram structure was destroyed. In contrast, modification of the ethyl groups in DS had no significant influence on its anticancer activity. Conclusions: The thiol groups and thiuram structure are indispensable for the anticancer activity of DS. The liver enrichment and metabolism may be the major obstruction for application of DS in cancer treatment. A delivery system to protect the thiol groups and development of novel soluble copper-DDC compound may pave the path for translation of DS into cancer therapeutics.This work was supported by grant from British Lung Foundation (RG14–8) and Innovate UK (104022).Published versio

Mapping quantitative trait loci (QTL) in sheep. II. Meta-assembly and identification of novel QTL for milk production traits in sheep

An (Awassi × Merino) × Merino backcross family of 172 ewes was used to map quantitative trait loci (QTL) for different milk production traits on a framework map of 200 loci across all autosomes. From five previously proposed mathematical models describing lactation curves, the Wood model was considered the most appropriate due to its simplicity and its ability to determine ovine lactation curve characteristics. Derived milk traits for milk, fat, protein and lactose yield, as well as percentage composition and somatic cell score were used for single and two-QTL approaches using maximum likelihood estimation and regression analysis. A total of 15 significant (P < 0.01) and additional 25 suggestive (P < 0.05) QTL were detected across both single QTL methods and all traits. In preparation of a meta-analysis, all QTL results were compared with a meta-assembly of QTL for milk production traits in dairy ewes from various public domain sources and can be found on the ReproGen ovine gbrowser http://crcidp.vetsci.usyd.edu.au/cgi-bin/gbrowse/oaries_genome/. Many of the QTL for milk production traits have been reported on chromosomes 1, 3, 6, 16 and 20. Those on chromosomes 3 and 20 are in strong agreement with the results reported here. In addition, novel QTL were found on chromosomes 7, 8, 9, 14, 22 and 24. In a cross-species comparison, we extended the meta-assembly by comparing QTL regions of sheep and cattle, which provided strong evidence for synteny conservation of QTL regions for milk, fat, protein and somatic cell score data between cattle and sheep