Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma

BACKGROUND: Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. HYPOTHESIS: Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. ANIMALS: Fourteen dogs with splenic HSA. METHODS: A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. RESULTS: All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. CONCLUSIONS AND CLINICAL IMPORTANCE: IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.     

Prevalence and identification of fungal DNA in the small intestine of healthy dogs and dogs with chronic enteropathies

Limited information is available about the prevalence and phylogenetic classification of fungal organisms in the gastrointestinal tract of dogs. Also, the impact of fungal organisms on gastrointestinal health and disease is not well understood. The aim of this study was to evaluate the prevalence of fungal DNA in the small intestine of healthy dogs and dogs with chronic enteropathies. Small intestinal content was analyzed from 64 healthy and 71 diseased dogs from five different geographic locations in Europe and the USA. Fungal DNA was amplified with panfungal primers targeting the internal transcriber spacer (ITS) region. PCR amplicons were subjected to phylogenetic analysis. Fungal DNA was detected in 60.9% of healthy dogs and in 76.1% of dogs with chronic enteropathies. This prevalence was not significantly different between the two groups (p=0.065). Fungal DNA was significantly more prevalent in mucosal brush samples (82.8%) than in luminal samples (42.9%; p=0.002). Sequencing results revealed a total of 51 different phylotypes. All sequences belonged to two phyla and were classified as either Ascomycota (32 phylotypes) or Basidiomycota (19 phylotypes). Three major classes were identified: Saccharomycetes, Dothideomycetes, and Hymenomycetes. The most commonly observed sequences were classified as Pichia spp., Cryptococcus spp., Candida spp., and Trichosporon spp. Species believed to be clinically more important were more commonly observed in diseased dogs. These results indicate a high prevalence and diversity of fungal DNA in the small intestine of both healthy dogs and dogs with chronic enteropathies. The canine gastrointestinal tract of diseased dogs may harbor opportunistic fungal pathogens.     

Pathogenicity determinants in smut fungi revealed by genome comparison

Biotrophic pathogens, such as the related maize pathogenic fungi Ustilago maydis and Sporisorium reilianum, establish an intimate relationship with their hosts by secreting protein effectors. Because secreted effectors interacting with plant proteins should rapidly evolve, we identified variable genomic regions by sequencing the genome of S. reilianum and comparing it with the U. maydis genome. We detected 43 regions of low sequence conservation in otherwise well-conserved syntenic genomes. These regions primarily encode secreted effectors and include previously identified virulence clusters. By deletion analysis in U. maydis, we demonstrate a role in virulence for four previously unknown diversity regions. This highlights the power of comparative genomics of closely related species for identification of virulence determinants.     

Wind dispersal of oribatid mites as a mode of migration

Oribatid mites are important colonizers of young soils, but little is known about their immigration pathways. In this study, one often-stated hypothesis was tested quantitatively: that wind is an important dispersal pathway. The aim was (1) to detect wind dispersal in oribatid mites (using sticky traps at different heights above ground level) and to determine factors influencing wind dispersal, (2) to investigate whether oribatids can survive wind dispersal and immigrate by wind into young soils (using mini-pitfall traps in test plots with oribatid-free substrate, active immigration being prohibited) and (3) to find out whether those oribatids are able to colonize young soils (using soil cores from the test plots). The results demonstrate (1) that mainly arboreal oribatid species were dispersed by wind - even at 160 m height - and can therefore be spread over large distances. Nevertheless, about 10% of the wind-dispersed oribatid mites belonged to species able to live in the soil and may therefore be potential colonizers of young soils. The number of specimen and species transported by wind was the highest close to the soil surface and the number of dispersed individuals was mainly influenced by seasonality and humidity. The results also suggest that the probability of a soil oribatid being dispersed by wind depends on its original microhabitat (tree habitats > soil surface > deeper soil layers) and its body weight. It was also shown that soil-dwelling oribatid mites survived wind dispersal and immigrated by wind into the test plots and that colonization of the test plots took at least 2 months longer than immigration. However, colonization success was low during the first 2 years of investigation and only Trichoribates incisellus was found several times in the nutrient-poor substrate. Therefore, wind dispersal is an important migration pathway, especially for arboreal oribatids. We suggest that immigration into young soils most likely occurs by repeated short-distance dispersal. Only some species are able to survive the hostile conditions of wind dispersal as well as of pioneer soils, but those that do are potentially the founders of new populations.     

Analyzing the effect of stepping stones on target patch colonisation in structured landscapes for Eurasian lynx

With habitat loss and fragmentation having become two of the major threats to the viability of species, the question of how to manage landscapes for species conservation has attracted much attention. In this context, the planning of stepping stones has been proposed to increase connectivity in fragmented landscapes. We present a simulation study with a neutral landscape approach to assess the effects of stepping stones on colonization success. To that end, we used a spatially explicit, calibrated population model of the European lynx (Lynx lynx) coupled with structured landscapes, in which we could control the landscape parameters of dispersal habitat coverage and contagion, as well as the number and size of stepping stones available for breeding. In general, we found that colonization success increased with increasing habitat coverage but decreased with increasing habitat contagion, while the introduction of stepping stones had significant effects in critical situations. Especially at low to medium dispersal habitat coverage and high disperser mortality, stepping stones had a positive effect on colonization success when they were large enough to produce new dispersers, but negative effects when they were small and located in a way that dispersers would be distracted from more suitable breeding habitat patches. The latter clearly constituted a shading effect and argues for a thorough consideration of the trade-offs related to stepping stone size and location when implementing stepping stones as a conservation measure, especially when the number of individuals of conservation concern is low.     

Quantification of stress sensitive markers in single fecal samples do not accurately predict excretion of these in the pig

All feces produced during 24 h were collected from five pigs and cortisol and immunoreactive cortisol metabolites (CICM), and IgA were quantified. Within pigs, the concentrations of CICM and IgA varied extensively between random samples obtained from a single fecal dropping, and deviated in most cases significantly from the true concentration measured in total fecal output (CV 6.7-130%). The CICM and IgA contents varied considerably (CV 8.1-114%) within and between individual fecal droppings from the same pig compared to the total fecal excretion. In conclusion, single random samples could not be used to reliably quantify the total fecal concentration or excretion of CICM or IgA in pigs. Analyses of all feces collected during shorter periods than 24 h did not provide an accurate estimate of the daily excretion of CICM. Thus, the concentration of stress sensitive molecules in random single fecal samples as an indicator of animal welfare should be interpreted with prudence.     

Ecosystem services in Swedish forests

We identify, describe qualitatively, quantify biophysically and, if possible, monetarily valuate the most important ecosystem services in Swedish forests. Existing Swedish and Nordic research and statistics within this area are reviewed and used to develop a first framework for the valuation of ecosystem services in Swedish forests. We base our analysis on the CICES framework and the Cascade-model. Despite the rather long occurrence and use of the concept of ecosystem services, we do not yet have enough information on the status and economic value of services in Swedish forests. The value of the forest ecosystem services is at best an indication of the different multifunctional objectives that should be met in the management of the Swedish forests. The five most central ecosystem services in Swedish forests according to annual flow are timber and pulpwood, bioenergy, game, climate regulation and recreation and training, each estimated to have a monetary value of several billion SEK. The different ecosystem services in multipurpose forests interact with each other and may lead to conflicts between use and conservation. We identified a number of trade-offs and synergies between services focusing on the five above ecosystem services.