Field evaluation of the efficacy and safety of emodepside/praziquantel spot-on solution against naturally acquired nematode and cestode infections in domestic cats.

Two controlled, blinded and randomized multi-site clinical field studies evaluated the efficacy and safety of emodepside/praziquantel spot-on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/praziquantel spot-on (Profender, Bayer AG, Leverkusen, Germany). For a positive-control product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/praziquantel spot-on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/praziquantel spot-on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/praziquantel spot-on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/praziquantel spot-on is highly efficacious and safe under field conditions.

Evaluation of the efficacy of emodepside plus praziquantel topical solution against ascarid infections (Toxocara cati or Toxascaris leonina) in cats.

Eleven controlled studies were conducted in the United States and Europe to evaluate the efficacy of a topical solution of emodepside (3 mg/kg)+praziquantel (12 mg/kg) (Profender, Bayer AG, Leverkusen, Germany) against infection with various stages of the ascarid nematodes Toxocara cati and Toxascaris leonina. Infections were induced by administration of larvated ascarid eggs, and stage-specific efficacy was evaluated by treating cats at scheduled intervals post-inoculation. All studies featured random allocation to treatment groups, placebo-treated control animals and assessment of outcome measures by masked personnel. The product (emodepside+praziquantel topical solution) was 100% effective against mature adults and immature adult T. cati. In addition, it was 96.8% effective against third stage larvae and at least 99.4% effective against fourth stage larvae of T. cati, respectively. Efficacy against mature, immature adult and L4 stages of T. leonina exceeded 93.4%, but regulatory "adequacy of infection" criteria were not met in some studies. No adverse reactions to treatment were noted in cats treated with the emodepside+praziquantel topical solution.

Efficacy of a topically administered combination of emodepside and praziquantel against mature and immature Ancylostoma tubaeforme in domestic cats.

This paper reports the efficacy of emodepside/praziquantel spot-on (Profender), Bayer AG, Leverkusen, Germany), a novel broad-spectrum anthelmintic for dermal application, against L4 larvae and immature adult and adult stages of Ancylostoma tubaeforme in cats. The formulation contains 2.14% (w/w) emodepside and 8.58% (w/v) praziquantel, with emodepside being active against gastrointestinal nematodes and praziquantel against cestodes. Five randomized, blinded and controlled laboratory studies demonstrated 100% efficacy of emodepside/praziquantel spot-on against mature A. tubaeforme and an efficacy of >95% and >97%, respectively, against L4 larvae and immature adults (based on worm counts after necropsy) at approximately the minimum proposed dose rate in cats of 3.0 mg emodepside and 12.0 mg praziquantel/kg body weight. No adverse reactions to the treatment were observed. It is concluded that emodepside/praziquantel spot-on is an effective and safe treatment against infections with mature and immature A. tubaeforme. Emodepside/praziquantel spot-on will considerably facilitate the treatment of cats against nematodes and cestodes compared with orally administered preparations.

Evaluation of the efficacy of emodepside+praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats.

Emodepside+praziquantel topical solution was developed to provide broad-spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and praziquantel (12 mg/kg) (Profender, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis, or experimental infections with Echinococcus multilocularis that were placebo-controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+praziquantel topical solution was 100% against D. caninum and T. taeniaeformis, and 98.5- 100% against E. multilocularis. No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+praziquantel topical solution was safe and highly effective against cestode infections.

Effect of a prolonged low-dose lipopolysaccharide infusion on feed intake and metabolism in heifers.

Prolonged infusions of bacterial lipopolysaccharides (LPS) are known to model gram-negative bacterial infections, but the basic mechanisms of the LPS effects on feed intake and metabolism and their potential interdependence are largely unknown. The aim of the present study was to distinguish and to better characterize the feeding suppressive and metabolic effects of LPS. Six heifers were infused intravenously for 100 min with either 1) LPS (2 microg/kg BW) with free access to feed, 2) saline with free access to feed, or 3) saline with feeding restricted to the amount of feed consumed after LPS infusion. Feed intake, body temperature, plasma concentrations of various metabolites and hormones, and the respiratory quotient and heat production were measured. The LPS reduced feed intake and induced pronounced changes in metabolic energy turnover and fat and carbohydrate metabolism that were largely independent of the concomitant feed intake reduction. Some of the metabolic changes were biphasic; the first phase resembled a stress response with increases in plasma glucose and cortisol, and the second phase reflected a beginning energy deficit with low plasma glucose and enhanced lipolysis. The coincidence of a short-term surge of plasma insulin with marked transient decreases in plasma FFA, glycerol, and beta-hydroxybutyrate as well as with the transition from hyper- to hypoglycemia indicates that insulin plays a role in some of the metabolic responses to LPS. The failure of LPS to clearly increase energy expenditure despite the increase in body temperature suggests that anaerobic mechanisms of heat production and, perhaps, a reduced peripheral blood flow contributed to the fever. Many of the initial metabolic responses occurred before and, therefore, independent of, an increase in circulating tumor necrosis factor-alpha.

Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

Morphologic and functional changes in bovine monocytes infected in vitro with the bovine leukaemia virus.

Experiments on the host cell spectrum of bovine leukaemia virus (BLV), a retrovirus closely related to the human T-cell leukaemia virus (HTLV), have yielded conflicting data. Currently, BLV is known to infect B cells, whereas its ability to infect other cell types, e.g. monocytes/macrophages, is doubtful. As monocytes/macrophages may have profound effects on the diversity of the T-cell response, we studied the possibility of in vitro infection, using bovine monocytes and SV40-transformed bovine macrophages. Proviral DNA was detected by nested polymerase chain reaction (PCR) from day 1 until the end of the experiments at either day 5 or day 80, depending on the quantity of virus used for infection. In addition, the infection was associated with morphological changes in infected cells as revealed by electron microscopy. The in vitro infection did not significantly change either the expression of surface antigens (CD11b, CD32, and major histocompatibility complex (MHC) class II) or the amounts of cytokine transcripts (interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, IL-6 and IL-12p40) with or without lipopolysaccharide (LPS) stimulation. The data suggest that BLV can infect monocytes, but the infection does not seem to influence the function or the phenotype of these cells. Infected monocytes may, however, play a role as a viral reservoir in vivo.