Efficacy of a spot-on combination containing 10% w/v imidacloprid and 1% w/v moxidectin for the treatment of troglostrongylosis in experimentally infected cats.

BACKGROUND: Parasitic bronchopneumonia in domestic cats in Europe, which can manifest with moderate to severe clinical signs, is frequently caused by Troglostrongylus brevior. Data on epizootiological and clinical relevance of cat troglostrongylosis have been published in the last decade but treatment options are still limited. Promising effectiveness data have been generated from clinical cases and field trials for a spot-on formulation containing 1% w/v moxidectin and 10% w/v imidacloprid (Advocate®, Elanco Animal Health). Therefore, two studies have been conducted to confirm under experimental conditions the efficacy of moxidectin 1% contained in Advocate® for the treatment of cat troglostrongylosis. METHODS: Sixteen and 20 cats experimentally infected with T. brevior were included in two separate studies, i.e., Study 1 and 2, respectively. Cats were infected with T. brevior third-stage larvae via gastric tube. In both studies cats were randomized to untreated (control, Group 1) and treatment (Group 2) groups. In Study 1 and Study 2, the two groups comprised eight and 10 cats each. Treated cats received Advocate® spot-on twice at a 4-week interval. The primary efficacy criterion was the number of viable adult T. brevior counted at necropsy. Throughout the trial, the fecal shedding of first-stage larvae (L1) was assessed in treated and untreated control cats. RESULTS: The experimental model was successful in both studies, as all cats started shedding T. brevior L1 within 25 days post-infection. At necropsy, T. brevior adults were found in 4/8 and 4/10 cats of the control groups in Study 1 and 2, respectively, while none of the treated cats harbored adult worms. The necropsy worm counts in controls did not meet relevant guideline requirements for adequacy of infection, with fewer than six infected cats in the control groups, thus limiting conclusions on treatment efficacy. The fact that 6/8 and 8/10 control cats in Study 1 and 2, respectively, shed L1 up to necropsy while larval shedding ceased in all treated animals after the first treatment provides supporting evidence on the level of efficacy. No remarkable adverse events were recorded in the two studies. CONCLUSION: These results indicate that Advocate® spot-on is a safe and effective option for treating cats infected by T. brevior.

Ceramide accumulation induces mitophagy and impairs ß-oxidation in PINK1 deficiency.

Energy production via the mitochondrial electron transport chain (ETC) and mitophagy are two important processes affected in Parkinson's disease (PD). Interestingly, PINK1, mutations of which cause early-onset PD, plays a key role in both processes, suggesting that these two mechanisms are connected. However, the converging link of both pathways currently remains enigmatic. Recent findings demonstrated that lipid aggregation, along with defective mitochondria, is present in postmortem brains of PD patients. In addition, an increasing body of evidence shows that sphingolipids, including ceramide, are altered in PD, supporting the importance of lipids in the pathophysiology of PD. Here, we identified ceramide to play a crucial role in PINK1-related PD that was previously linked almost exclusively to mitochondrial dysfunction. We found ceramide to accumulate in mitochondria and to negatively affect mitochondrial function, most notably the ETC. Lowering ceramide levels improved mitochondrial phenotypes in pink1-mutant flies and PINK1-deficient patient-derived fibroblasts, showing that the effects of ceramide are evolutionarily conserved. In addition, ceramide accumulation provoked ceramide-induced mitophagy upon PINK1 deficiency. As a result of the ceramide accumulation, ß-oxidation in PINK1 mutants was decreased, which was rescued by lowering ceramide levels. Furthermore, stimulation of ß-oxidation was sufficient to rescue PINK1-deficient phenotypes. In conclusion, we discovered a cellular mechanism resulting from PD-causing loss of PINK1 and found a protective role of ß-oxidation in ETC dysfunction, thus linking lipids and mitochondria in the pathophysiology of PINK1-related PD. Furthermore, our data nominate ß-oxidation and ceramide as therapeutic targets for PD.

Subiculum as a generator of sharp wave-ripples in the rodent hippocampus.

Sharp wave-ripples (SWRs) represent synchronous discharges of hippocampal neurons and are believed to play a major role in memory consolidation. A large body of evidence suggests that SWRs are exclusively generated in the CA3-CA2 network. In contrast, here, we provide several lines of evidence showing that the subiculum can function as a secondary SWRs generator. SWRs with subicular origin propagate forward into the entorhinal cortex as well as backward into the hippocampus proper. Our findings suggest that the output structures of the hippocampus are not only passively facilitating the transfer of SWRs to the cortex, but they also can actively contribute to the genesis of SWRs. We hypothesize that SWRs with a subicular origin may be important for the consolidation of information conveyed to the hippocampus via the temporoammonic pathway.

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

Canonical goal-selective representations are absent from prefrontal cortex in a spatial working memory task requiring behavioral flexibility.

The prefrontal cortex (PFC)'s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate - after distractions and a delay - to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form - that is differences in the rate, sequence, phase, or covariance of firing. This suggests that such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.

Rapid Target Binding and Cargo Release of Activatable Liposomes Bearing HER2 and FAP Single-Chain Antibody Fragments Reveal Potentials for Image-Guided Delivery to Tumors.

Liposomes represent suitable tools for the diagnosis and treatment of a variety of diseases, including cancers. To study the role of the human epidermal growth factor receptor 2 (HER2) as target in cancer imaging and image-guided deliveries, liposomes were encapsulated with an intrinsically quenched concentration of a near-infrared fluorescent dye in their aqueous interior. This resulted in quenched liposomes (termed LipQ), that were fluorescent exclusively upon degradation, dye release, and activation. The liposomes carried an always-on green fluorescent phospholipid in the lipid layer to enable tracking of intact liposomes. Additionally, they were functionalized with single-chain antibody fragments directed to fibroblast activation protein (FAP), a marker of stromal fibroblasts of most epithelial cancers, and to HER2, whose overexpression in 20-30% of all breast cancers and many other cancer types is associated with a poor treatment outcome and relapse. We show that both monospecific (HER2-IL) and bispecific (Bi-FAP/HER2-IL) formulations are quenched and undergo HER2-dependent rapid uptake and cargo release in cultured target cells and tumor models in mice. Thereby, tumor fluorescence was retained in whole-body NIRF imaging for 32-48 h post-injection. Opposed to cell culture studies, Bi-FAP/HER2-IL-based live confocal microscopy of a high HER2-expressing tumor revealed nuclear delivery of the encapsulated dye. Thus, the liposomes have potentials for image-guided nuclear delivery of therapeutics, and also for intraoperative delineation of tumors, metastasis, and tumor margins.

Efficacy of imidacloprid 10%/moxidectin 1% spot-on formulation (Advocate®) in the prevention and treatment of feline aelurostrongylosis.

BACKGROUND: In three randomized, controlled laboratory efficacy studies, the efficacy in the prevention of patent infections of a topical combination of imidacloprid 10%/moxidectin 1% (Advocate® spot-on formulation for cats, Bayer Animal Health GmbH) against larval stages and immature adults of Aelurostrongylus abstrusus, as well as the treatment efficacy of a single or three monthly treatments against adult A. abstrusus, were evaluated. METHODS: Cats were experimentally inoculated with 300-800 third-stage larvae (L3). Each group comprised 8 animals and the treatment dose was 10 mg/kg bodyweight (bw) imidacloprid and 1 mg/kg bw moxidectin in each study. Prevention of the establishment of patent infections was evaluated by two treatments at a monthly interval at three different time points before and after challenge infection. Curative efficacy was tested by one or three treatments after the onset of patency. Worm counts at necropsy were used for efficacy calculations. RESULTS: In Study 1, the control group had a geometric mean (GM) of 28.8 adult nematodes and the single treatment group had a GM of 3.4 (efficacy 88.3%). In Study 2, the control group had a GM of 14.3, the prevention group had a GM of 0 (efficacy 100%), while the treatment group had a GM of 0.1 (efficacy 99.4%). In Study 3, the GM worm burden in the control group was 32.6 compared to 0 in all three prevention groups (efficacy 100% for all of those groups). CONCLUSIONS: The monthly administration of Advocate® reliably eliminated early larval stages and thereby prevented lung damage from and patent infections with A. abstrusus in cats. Regarding treatment, a single application of Advocate® reduced the worm burden, but it did not sufficiently clear the infection. In contrast, three monthly treatments were safe and highly efficacious against A. abstrusus.

Routes to, from and within the subiculum.

The subiculum is one of the major output areas of the hippocampus and has extensive projections to extrahippocampal targets. It is likely to play a pivotal role in the distribution of outgoing information from the hippocampus. The hippocampus, including the subiculum, is important for the formation, consolidation and retrieval of memory. These functions require a network that is flexible enough to encode incoming information and also allows for reliable distribution, storage and integration into previously encoded memories. Finally, relevant information has to be retrieved in a context-specific manner to allow for an appropriate behavioral response. The subiculum as a gateway between the hippocampus and cortex might serve to integrate and process information from the hippocampus proper and its other inputs before conveying it to more permanent storage locations. This review summarizes how the subiculum is embedded into upstream and downstream circuits, describes what is known about the local network topology and discusses cellular and functional properties of subicular cells subtypes. Lastly, it describes how these properties might help to separate information into parallel output streams and distribute it to its multiple target areas.

10-year parasitological examination results (2003 to 2012) of faecal samples from horses, ruminants, pigs, dogs, cats, rabbits and hedgehogs.

The results of coproscopical examinations in domestic animals and hedgehogs carried out as routine diagnostics in the years 2003 to 2012 at the Institute for Parasitology, University of Veterinary Medicine Hannover, Germany, are presented. Of 3475 horse faecal samples, 30.1% contained stages of strongyles and 1.3% eggs of Strongyloides westeri and Parascaris equorum, respectively. The most frequently observed parasite stages in 1416 cattle faecal samples were Eimeria oocysts (21.3%) and strongyle eggs or larvae (15.9%). Dictyocaulus viviparus larvae and Fasciola hepatica eggs were identified in 0.9 and 1.3% of samples. Of 574 bovine faecal samples analysed by carbol-fuchsin staining, 39.9% were positive for Cryptosporidium oocysts. Stages of strongyles were found in 52.4% of sheep (n = 374) and 44.9% of goat faeces (n = 98) and Eimeria oocysts in 41.4 and 32.7% of their faeces, respectively. Of 1848 pig faecal samples, 3.0% contained stages of strongyles, 1.6% eggs of Ascaris suum and 3.3% coccidian (Eimeria or Cystoisospora spp.) oocysts. The most frequently detected helminth eggs in faecal samples of dogs (n = 2731) and cats (n = 903) were Toxocara spp. (2.8 and 3.9%, respectively). Cystoisospora oocysts were identified in 5.6% of dog and 2.4% of cat faeces. Furthermore, 0.7% of the cat samples were positive for small Toxoplasma gondii-like oocysts. The faecal samples of rabbits (n = 434) contained eggs of Passalurus ambiguus (3.0%), strongyles (1.8%) and Trichuris leporis (0.2%) as well as Eimeria oocysts (21.2%). The most abundant nematodes in the samples of hedgehogs (n = 205) were Capillaria spp. (39.5%) and Crenosoma striatum (26.8%); coccidian oocysts were found in 14.2% of the samples.

Activatable bispecific liposomes bearing fibroblast activation protein directed single chain fragment/Trastuzumab deliver encapsulated cargo into the nuclei of tumor cells and the tumor microenvironment simultaneously.

Molecular targeting plays a significant role in cancer diagnosis and therapy. However, the heterogeneity of tumors is a limiting obstacle for molecular targeting. Consequently, clinically approved drug delivery systems such as liposomes still rely on passive targeting to tumors, which does not address tumor heterogeneity. In this work, we therefore designed and elucidated the potentials of activatable bispecific targeted liposomes for simultaneous detection of fibroblast activation protein (FAP) and the human epidermal growth factor receptor 2 (HER2). The bispecific liposomes were encapsulated with fluorescence-quenched concentrations of the near-infrared fluorescent dye, DY-676-COOH, making them detectable solely post processing within target cells. The liposomes were endowed with a combination of single chain antibody fragments specific for FAP and HER2 respectively, or with the FAP single chain antibody fragment in combination with Trastuzumab, which is specific for HER2. The Trastuzumab based bispecific formulation, termed Bi-FAP/Tras-IL revealed delivery of the encapsulated dye into the nuclei of HER2 expressing cancer cells and caused cell death at significantly higher rates than the free Trastuzumab. Furthermore, fluorescence imaging and live microscopy of tumor models in mice substantiated the delivery of the encapsulated cargo into the nuclei of target tumor cells and tumor stromal fibroblasts. Hence, they convey potentials to address tumor plasticity, to improve targeted cancer therapy and reduce Trastuzumab resistance in the future. STATEMENT OF SIGNIFICANCE: This work demonstrates the design of activatable bispecific liposomes aimed to target HER2, a poor prognosis tumor marker in many tumor types, and fibroblast activation protein (FAP), a universal tumor marker overexpressed on tumor fibroblasts and pericytes of almost all solid tumors. Encapsulating liposomes with a quenched concentration of a NIRF dye which only fluoresced after cellular degradation and activation enabled reliable visualization of the destination of the cargo in cells and animal studies. Conjugating single chain antibody fragments directed to FAP, together with Trastuzumab, a humanized monoclonal antibody for HER2 resulted in the activatable bispecific liposomes. In animal models of xenografted human breast tumors, the remarkable ability of the bispecific probes to simultaneously deliver the encapsulated dye into the nuclei of target tumor cells and tumor fibroblasts could be demonstrated. Hence, the bispecific probes represent model tools with high significance to address tumor heterogeneity and manage Trastuzumab resistance in the future.

Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency.

PINK1 is mutated in Parkinson's disease (PD), and mutations cause mitochondrial defects that include inefficient electron transport between complex I and ubiquinone. Neurodegeneration is also connected to changes in lipid homeostasis, but how these are related to PINK1-induced mitochondrial dysfunction is unknown. Based on an unbiased genetic screen, we found that partial genetic and pharmacological inhibition of fatty acid synthase (FASN) suppresses toxicity induced by PINK1 deficiency in flies, mouse cells, patient-derived fibroblasts, and induced pluripotent stem cell-derived dopaminergic neurons. Lower FASN activity in PINK1 mutants decreases palmitate levels and increases the levels of cardiolipin (CL), a mitochondrial inner membrane-specific lipid. Direct supplementation of CL to isolated mitochondria not only rescues the PINK1-induced complex I defects but also rescues the inefficient electron transfer between complex I and ubiquinone in specific mutants. Our data indicate that genetic or pharmacologic inhibition of FASN to increase CL levels bypasses the enzymatic defects at complex I in a PD model.

A fast and effective determination of the biodistribution and subcellular localization of fluorescent immunoliposomes in freshly excised animal organs.

BACKGROUND: Preclinical research implementing fluorescence-based approaches is inevitable for drug discovery and technology. For example, a variety of contrast agents developed for biomedical imaging are usually evaluated in cell systems and animal models based on their conjugation to fluorescent dyes. Biodistribution studies of excised organs are often performed by macroscopic imaging, whereas the subcellular localization though vital, is often neglected or further validated by histological procedures. Available systems used to define the subcellular biodistribution of contrast agents such as intravital microscopes or ex vivo histological analysis are expensive and not affordable by the majority of researchers, or encompass tedious and time consuming steps that may modify the contrast agents and falsify the results. Thus, affordable and more reliable approaches to study the biodistribution of contrast agents are required. We developed fluorescent immunoliposomes specific for human fibroblast activation protein and murine endoglin, and used macroscopic fluorescence imaging and confocal microscopy to determine their biodistribution and subcellular localization in freshly excised mice organs at different time points post intravenous injection. RESULTS: Near infrared fluorescence macroscopic imaging revealed key differences in the biodistribution of the respective immunoliposomes at different time points post injection, which correlated to the first-pass effect as well as the binding of the probes to molecular targets within the mice organs. Thus, a higher accumulation and longer retention of the murine endoglin immunoliposomes was seen in the lungs, liver and kidneys than the FAP specific immunoliposomes. Confocal microscopy showed that tissue autofluorescence enables detection of organ morphology and cellular components within freshly excised, non-processed organs, and that fluorescent probes with absorption and emission maxima beyond the tissue autofluorescence range can be easily distinguished. Hence, the endoglin targeting immunoliposomes retained in some organs could be detected in the vascular endothelia cells of the organs. CONCLUSIONS: The underlying work represents a quick, effective and more reliable setup to validate the macroscopic and subcellular biodistribution of contrast agents in freshly excised animal organs. The approach will be highly beneficial to many researchers involved in nanodrug design or in fluorescence-based studies on disease pathogenesis.

Exploring Possibilities for Transforming Established Subscription-based Scientific Journals into Open Access Journals. Present Situation, Transformation Criteria, and Exemplary Implementation within Trans-O-MIM.

BACKGROUND: Based on today's information and communication technologies the open access paradigm has become an important approach for adequately communicating new scientific knowledge. OBJECTIVES: Summarizing the present situation for journal transformation. Presenting criteria for adequate transformation as well as a specific approach for it. Describing our exemplary implementation of such a journal transformation. METHODS: Studying the respective literature as well as discussing this topic in various discussion groups and meetings (primarily of editors and publishers, but also of authors and readers), with long term experience as editors and /or publishers of scientific publications as prerequisite. RESULTS: There is a clear will, particularly of political and funding organizations, towards open access publishing. In spite of this, there is still a large amount of scientific knowledge, being communicated through subscription-based journals. For successfully transforming such journals into open access, sixteen criteria for a goal-oriented, stepwise, sustainable, and fair transformation are suggested. The Tandem Model as transformation approach is introduced. Our exemplary implementation is done in the Trans-O-MIM project. It is exploring strategies, models and evaluation metrics for journal transformation. As instance the journal Methods of Information in Medicine will apply the Tandem Model from 2017 onwards. CONCLUSIONS: Within Trans-O-MIM we will reach at least nine of the sixteen criteria for adequate transformation. It was positive to implement Trans-O-MIM as international research project. After first steps for transforming Methods have successfully been made, challenges will remain, among others, in identifying appropriate incentives for open access publishing in order to support its transformation.

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset.

Cell-specific synaptic plasticity induced by network oscillations.

Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner.

Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.

Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.

Functional Diversity of Subicular Principal Cells during Hippocampal Ripples.

Cortical and hippocampal oscillations play a crucial role in the encoding, consolidation, and retrieval of memory. Sharp-wave associated ripples have been shown to be necessary for the consolidation of memory. During consolidation, information is transferred from the hippocampus to the neocortex. One of the structures at the interface between hippocampus and neocortex is the subiculum. It is therefore well suited to mediate the transfer and distribution of information from the hippocampus to other areas. By juxtacellular and whole-cell-recordings in awake mice, we show here that in the subiculum a subset of pyramidal cells is activated, whereas another subset is inhibited during ripples. We demonstrate that these functionally different subgroups are predetermined by their cell subtype. Bursting cells are selectively used to transmit information during ripples, whereas the firing probability in regular firing cells is reduced. With multiple patch-clamp recordings in vitro, we show that the cell subtype-specific differences extend into the local network topology. This is reflected in an asymmetric wiring scheme where bursting cells and regular firing cells are recurrently connected among themselves but connections between subtypes exclusively exist from regular to bursting cells. Furthermore, inhibitory connections are more numerous onto regular firing cells than onto bursting cells. We conclude that the network topology contributes to the observed functional diversity of subicular pyramidal cells during sharp-wave associated ripples. SIGNIFICANCE STATEMENT: Memory consolidation is dependent on hippocampal activity patterns, so called hippocampal ripples. During these fast oscillations, memory traces are transferred from the hippocampus to the neocortex via the subiculum. We investigated the role of single cells in the subiculum during ripples and found that, dependent on their subtype, they are preferentially activated or inhibited. In addition, these two subtypes, the bursting and regular firing type, are differentially integrated into the local network: inhibitory cells are more densely connected to regular firing cells, and communication between regular and bursting cells is unidirectional. Together with earlier findings on different preferential target regions of these subtypes, we conclude that memory traces are guided to target regions of the activated cell type.

Susceptibility of Adult Cat Fleas (Siphonaptera: Pulicidae) to Insecticides and Status of Insecticide Resistance Mutations at the Rdl and Knockdown Resistance Loci.

The susceptibility of 12 field-collected isolates and 4 laboratory strains of cat fleas, Ctenocephalides felis was determined by topical application of some of the insecticides used as on-animal therapies to control them. In the tested field-collected flea isolates the LD50 values for fipronil and imidacloprid ranged from 0.09 to 0.35 ng/flea and 0.02 to 0.19 ng/flea, respectively, and were consistent with baseline figures published previously. The extent of variation in response to four pyrethroid insecticides differed between compounds with the LD50 values for deltamethrin ranging from 2.3 to 28.2 ng/flea, etofenprox ranging from 26.7 to 86.7 ng/flea, permethrin ranging from 17.5 to 85.6 ng/flea, and d-phenothrin ranging from 14.5 to 130 ng/flea. A comparison with earlier data for permethrin and deltamethrin implied a level of pyrethroid resistance in all isolates and strains. LD50 values for tetrachlorvinphos ranged from 20.0 to 420.0 ng/flea. The rdl mutation (conferring target-site resistance to cyclodiene insecticides) was present in most field-collected and laboratory strains, but had no discernible effect on responses to fipronil, which acts on the same receptor protein as cyclodienes. The kdr and skdr mutations conferring target-site resistance to pyrethroids but segregated in opposition to one another, precluding the formation of genotypes homozygous for both mutations.

Efficacy of Emodepside/Praziquantel Spot-on (Profender®) against adult Aelurostrongylus abstrusus Nematodes in Experimentally Infected Cats.

The adulticidal efficacy of a topical combination of emodepside 2.1 % (w/v) plus praziquantel 8.6 % (w/v) (Profender® spot-on for cats, Bayer) against adult Aelurostrongylus abstrusus nematodes was evaluated in two randomised, placebo-controlled laboratory efficacy studies. Each study involved 16 cats experimentally inoculated with L3 (800 and 600 each in studies no. 1 and 2, respectively) and randomised into two study groups of 8 cats each after onset of patency. While cats in the treatment group in study no. 1 received a single spot-on application at the minimum therapeutic dose (3 mg/kg emodepside and 12 mg/kg praziquantel), cats in study no. 2 were treated twice with an interval of 14 days. The faecal output of first stage larvae was monitored throughout the study. Necropsy was conducted 4 or 5 weeks after the (first) treatment and the worm counts were used for efficacy calculations. The control groups showed a geometric mean of the total worm count (live and dead worms) of 28.8 (study no. 1) and 17.6 (study no. 2), respectively. All control animals were infected. While the single treatment in study no. 1 resulted in a reduction of the total worm burden by 73.0 % (p = 0.0070), the treatment protocol in study no. 2 was 99.2 % effective (p = 0.0035). Based on live worm counts, the efficacy in study no. 2 was 100 % (p = 0.0030). It is concluded that two applications of Profender® spot-on given two weeks apart represent a safe and highly efficacious treatment regime against feline aelurostrongylosis.