Reversal of neuromuscular block in companion animals

ObjectiveTo review the evidence regarding the reversal of neuromuscular block (NMB) in companion animals with emphasis on the development and use of newer agents.Database usedData sources include scientific reviews and original research publications in both human and veterinary literature using Pubmed and Scopus as search data bases. Unpublished and locally published data on reversal of NMB are presented.ConclusionsResidual NMB has been shown to increase morbidity and mortality in humans and needs to be avoided. It can be detected only by adequate neuromuscular monitoring. The proper use of reversal agents avoids residual NMB and recurarization should not occur. Anticholinesterase inhibitors, such as edrophonium and neostigmine have been used to reverse NMB when the need for this has been established. Reversal is influenced by several factors and a number of undesirable side- effects of these drugs have been reported. Sugammadex, a γ-cyclodextrin, which was designed specifically to encapsulate rocuronium, is more rapid in its actions, has fewer side effects and can reverse profound NMB induced by aminosteroidal muscle relaxants.     

In search for the ecological and toxicological relevance of sediment re-mobilisation and transport during flood events

In response to increasing concerns about the potential toxicological impacts of (extreme) flood events, scientists from several disciplines have joined to form the interdisciplinary research project named FLOODSEARCH. FLOODSEARCH is one of the recent Pathfinder Projects supported by the German Excellence Initiative via the Exploratory Research Space at RWTH Aachen (ERS). FLOODSEARCH aims to combine methodologies of hydraulic engineering and ecotoxicology in a new interdisciplinary approach to assess the risks associated with the re-mobilisation of particulate bound contaminants often observed after severe flood events. Impacts of extreme flood events and aspects of re-mobilisation of sediment-bound toxic compounds will be characterised and evaluated in controlled experiments fusing flood simulation technologies with biological effects assessment. The overall goal is to establish a novel and more realistic approach towards flood event testing that can be applied to a number of different questions and species. Specifically, model aquatic species such as rainbow trout (Onchorhynchus mykiss) will be exposed to particle-bound contaminants in flood-like conditions in a specifically designed annular flume that permits monitoring of both physical/chemical and biological parameter. Ultimately, this approach will assist to further our understanding of the potential biological risks associated with increasingly frequent extreme flood events, e.g., as a consequence of climate change, by bridging the gap between the physical (re-)mobilisation of contaminants and resulting toxicological impacts on aquatic organisms. Thus, it is the objective of the project to derive relationships between the hydrodynamic parameters such as velocities and turbulences, the parameters associated to sediment transport such as sediment concentration and grain sizes and the biological parameters.     

Determination of lignans in edible and nonedible parts of pomegranate (Punica granatum L.) and products derived therefrom, particularly focusing on the quantitation of isolariciresinol using HPLC-DAD-ESI/MSn

A method for the characterization and quantitation of phyto-estrogenic lignans from pomegranate (Punica granatum L.) fruits and fruit-derived products by HPLC-DAD-MS(n) was developed. For this purpose, edible and nonedible parts of pomegranate (aril, peel, mesocarp, seed, and twigs), commercial juices, juices produced on pilot-plant scale, and encapsulated dietary supplements were analyzed. In addition to the peel, mesocarp, and twigs, lignans were detected in two juices obtained from entire fruits, four commercial juices, and three encapsulated pomegranate extracts. Isolariciresinol was the predominant lignan with contents of 5.0, 10.5, and 45.8 mg/kg dry matter in processed pomegranate mesocarp, peel, and twigs, respectively. In contrast, due to their low amounts, quantitation of lignans in pomegranate products was impossible. Therefore, contrary to previous assumptions, lignans were found to be less relevant in pomegranate-derived products. However, the byproduct from pomegranate processing may be used for lignan extraction. The method presented allows one to differentiate between pomegranate-derived products obtained from fruits without peels or by dejuicing applying low pressures, which were devoid of lignans, and those obtained from entire fruits applying high pressures, thus containing lignans. Consequently, this study helps to optimize process technology aiming at the recovery of preparations with well-desired compositions, which may reduce the risk of a wide range of diseases, such as certain types of cancer.     

The genome of the African trypanosome Trypanosoma brucei

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.     

Metabolism and persistence of atrazine in several field soils with different atrazine application histories

To assess the potential occurrence of accelerated herbicide degradation in soils, the mineralization and persistence of (14)C-labeled and nonlabeled atrazine was evaluated over 3 months in two soils from Belgium (BS, atrazine-treated 1973-2008; BC, nontreated) and two soils from Germany (CK, atrazine-treated 1986-1989; CM, nontreated). Prior to the experiment, accelerated solvent extraction of bulk field soils revealed atrazine (8.3 and 15.2 μg kg(-1)) in BS and CK soils and a number of metabolites directly after field sampling, even in BC and CM soils without previous atrazine treatment, by means of LC-MS/MS analyses. For atrazine degradation studies, all soils were incubated under different moisture conditions (50% maximum soil water-holding capacity (WHC(max))/slurried conditions). At the end of the incubation, the (14)C-atrazine mineralization was high in BS soil (81 and 83%) and also unexpectedly high in BC soil (40 and 81%), at 50% WHC(max) and slurried conditions, respectively. In CK soil, the (14)C-atrazine mineralization was higher (10 and 6%) than in CM soil (4.7 and 2.7%), but was not stimulated by slurried conditions. The results revealed that atrazine application history dramatically influences its degradation and mineralization. For the incubation period, the amount of extractable atrazine, composed of residues from freshly applied atrazine and residues from former field applications, remained significantly greater (statistical significance = 99.5 and 99.95%) for BS and CK soils, respectively, than the amount of extractable atrazine in the bulk field soils. This suggests that (i) mostly freshly applied atrazine is accessible for a complex microbial community, (ii) the applied atrazine is not completely mineralized and remains extractable even in adapted soils, and (iii) the microbial atrazine-mineralizing capacity strongly depends on atrazine application history and appears to be conserved on long time scales after the last application.     

Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles

Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse. CpG-ODN delivery by gelatin nanoparticles (GNPs) resulted in enhanced cellular uptake in murine and human in vitro studies and was a starting point for the present trial. The aim of this study was to identify an optimal stimulating CpG motif in horses with regard to species specificity on equine bronchoalveolar lavage (BAL) cells, in terms of a possible specific immunomodulation effect (Th2/Th1 shift) by used CpG-ODN. Accordingly, GNPs were evaluated as a delivery system to improve CpG-ODN immunostimulation in equine BAL cells. BAL fluid (BALF) was obtained from seven horses with moderate RAO and from four healthy horses and was subsequently incubated with five different CpG-ODN sequences (from A-, B- and C-class) and one ODN without any CpG motif. Release of three key cytokines (IL-4, IL-10 and IFN-γ) was quantified by ELISA to detect an allergy mediated Th2 immunoresponse (IL-4) as well as a proinflammatory Th1 response (IFN-γ). Due to its specific anti-inflammatory and anti-allergic effects, IL-10 was considered as a beneficial agent in pathophysiology of RAO. Results showed a significant upregulation of IL-10 and IFN-γ on the one hand and a downregulation of IL-4 on the other hand in RAO affected horses. Cell cultures from healthy horses had a significantly stronger response in cytokine release to all the applied stimuli in contrast to RAO derived cells. Comparing all five CpG sequences, A-class 2216 significantly showed the highest immunomodulatory effects on equine BALF cells and, hence, was chosen for follow-up preliminary clinical studies.     

Neuromuscular blockade with rocuronium bromide for ophthalmic surgery in horses

Purpose The production of a central eye to ease surgical access for intraocular surgery is generally dependent on the depth of anesthesia. The aim of this study was to evaluate the eyeball position under muscle relaxation with rocuronium during general anesthesia. Material and methods Twenty horses, body weight 480 ± 62 kg; age 12.6 ± 6.2 years (mean ± SD) were anesthetised for various ophthalmic surgeries. Horses were premedicated with acepromazine, xylazine, and butorphanol intravenously and anesthesia induced with ketamine and diazepam. Anesthesia was maintained with isoflurane in 100% oxygen and 0.6 mL/kg/h of an infusion containing midazolam, ketamine, and xylazine diluted in 500 mL 0.9% NaCl. Horses were mechanically ventilated. Neuromuscular function was assessed with an acceleromyograph (TOF‐Guard^®) and the N. peroneus superficialis was stimulated every 15 s with a train‐of‐four stimulation pattern. A dose of 0.3 mg/kg rocuronium was administered intravenously. The changes in the eyeball position were recorded. Results The dose of 0.3 mg/kg rocuronium produced a 100% neuromuscular block in all horses. Onset time and clinical duration of block was 2.38 ± 2.02 min (range 0.5–8) and 32 ± 18.6 min (range 7.7–76.2), respectively. The globe rotated to central position within 31 ± 2.8 s. The whole iris was visible after 42 ± 7.7 s in all horses. No additional bolus of rocuronium was necessary for any surgery. Conclusion Neuromuscular blockade with rocuronium bromide can be used safely to facilitate ophthalmic surgery in equines.     

Anthropogenic pollutants affect ecosystem services of freshwater sediments: the need for a “triad plus x” approach

Purpose  

Freshwater sediments and their attached microbial communities (biofilms) are essential features of rivers and lakes, providing valuable ecosystem services such as nutrient recycling or self-purification which extend beyond the aquatic environment. Anthropogenic pollutants, whether from the industrial era or as a result of our contemporary lifestyles, can negatively affect these functions with hitherto unknown consequences on ecology, the economy and human health. Thus far, the singular view of the involved disciplines such as ecotoxicology, environmental microbiology, hydrology and geomorphology has prevented a deeper understanding of this emerging issue.     

Gene targeting in stem cells from individuals with osteogenesis imperfecta

Adult stem cells offer the potential to treat many diseases through a combination of ex vivo genetic manipulation and autologous transplantation. Mesenchymal stem cells (MSCs, also referred to as marrow stromal cells) are adult stem cells that can be isolated as proliferating, adherent cells from bones. MSCs can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, making them ideal candidates for a variety of cell-based therapies. Here, we have used adeno-associated virus vectors to disrupt dominant-negative mutant COL1A1 collagen genes in MSCs from individuals with the brittle bone disorder osteogenesis imperfecta, demonstrating successful gene targeting in adult human stem cells.