Efficacy of a new spot-on formulation of selamectin plus sarolaner against Ancylostoma tubaeforme and Toxocara cati in cats

The efficacy of a new spot-on formulation of selamectin plus sarolaner for cats was evaluated against induced infections with Ancylostoma tubaeforme (hookworm) and Toxocara cati (roundworm). Five laboratory studies were conducted using adult, purpose-bred cats. Four of the studies were designed to evaluate efficacy of the combination against A. tubaeforme, the dose-limiting gastrointestinal nematode species for selamectin. In two of these studies non-interference between selamectin and sarolaner was also evaluated. The fifth study evaluated efficacy of the combination against mixed infections of A. tubaeforme and T. cati. The hookworm isolates in three studies were of US origin, as was the roundworm isolate. In the two remaining studies, cats were inoculated with a hookworm isolate of European origin. Cats were inoculated with 150 (±50) to 200 (±50) infective hookworm larvae 30–42 days prior to treatment and with 400 infective roundworm eggs 60 days prior to treatment. Cats were ranked by pre-treatment faecal egg counts and randomly allocated to different treatment groups. In all studies, cats were treated at the minimum label dose to provide 6.0 mg selamectin per kg bodyweight. All animals were euthanized 7–10 days after treatment for worm counts. Efficacy was calculated based on the reduction of the geometric mean worm counts in the treated groups versus the placebo-treated control groups. The efficacy against adult hookworms was 99.2%, 94.3% and 100% in three of these studies, and was lower in the remaining two studies. The efficacy against T. cati was 100%. Furthermore, non-interference between sarolaner and selamectin was demonstrated. Thus, a single topical application of the new spot-on formulation of selamectin plus sarolaner at the minimum label dose is effective in the treatment of adult hookworm and roundworm infections in cats

Efficacy of a new spot-on formulation of selamectin plus sarolaner against four common tick species infesting cats in Europe

A single application of a new spot-on formulation of selamectin plus sarolaner (Stronghold®Plus, Zoetis) was evaluated for efficacy against the most common tick species infesting cats in Europe. In each of the seven laboratory studies, 16 adult and purpose-bred cats were randomly allocated to one of two treatment groups based on pre-treatment tick counts. Weekly infestations with 50 unfed adult Ixodes ricinus (2 studies), Ixodes hexagonus (1 study), Dermacentor reticulatus (2 studies), or Rhipicephalus sanguineus (2 studies) were scheduled on Days −2, 5, 12, 19, 26 and 33. Cats were treated on Day 0 with the spot-on formulation at the minimum recommended label dose of 6.0 mg selamectin and 1.0 mg sarolaner per kg bodyweight or with a placebo. Ticks were counted 48 h after treatment and after each re-infestation. No treatment-related adverse reactions were recorded in any of the studies. Geometric mean live tick counts were significantly (P ≤ 0.0012) lower in the selamectin/sarolaner-treated group compared to the placebo-treated group at all time-points. Against I. ricinus and I. hexagonus, efficacy was ≥97.2% against existing infestations and ≥97.4% against weekly re-infestations for at least 5 weeks. Treatment was 100% effective against existing R. sanguineus infestations and was ≥95.8% for at least 4 weeks. Against D. reticulatus treatment resulted in ≥94.4% efficacy for at least 4 weeks. Thus, a single application of the new spot-on formulation of selamectin plus sarolaner at the minimum dose provides rapid treatment of existing infestations and is at least one month effective against re-infestation by all relevant European tick species in cats

Identification and safety effects of road user related measures. Deliverable 4.2 of the H2020 project SafetyCube

Safety CaUsation, Benefits and Efficiency (SafetyCube) is a European Commission supported Horizon 2020 project with the objective of developing an innovative road safety Decision Support System (DSS). The DSS will enable policy-makers and stakeholders to select and implement the most appropriate strategies, measures, and cost-effective approaches to reduce casualties of all road user types and all severities. This document is the second deliverable (4.2) of work package 4, which is dedicated to identifying and assessing road safety measures related to road users in terms of their effectiveness. The focus of deliverable 4.2 is on the identification and assessment of countermeasures and describes the corresponding operational procedure and outcomes. Measures which intend to increase road safety of all kind of road user groups have been considered [...continues]

Antimicrobial susceptibility and characterization of outer membrane proteins of Haemophilus ducreyi isolated in Thailand

One hundred strains of Haemophilus ducreyi isolated in Thailand from patients with chancroid were tested by the agar dilution method against 10 antimicrobial agents and typed by outer membrane protein pattern by using sodium dodecyl sulfate gel electrophoresis. All strains produced beta-lactamase and were resistant to tetracycline, kanamycin, and sulfonamides. Most had a decreased susceptibility to trimethoprim (MIC for 50% of the strains [MIC50], 0.5 micrograms/ml) and chloramphenicol (MIC50, 8 micrograms/ml). Strains were susceptible to ciprofloxacin (MIC90, 0.001 micrograms/ml), ceftriaxone (MIC50, 0.0015 micrograms/ml), erythromycin (MIC50, 0.015 micrograms/ml), rosoxacin (MIC50, 0.03 micrograms/ml), and spectinomycin (MIC50, 8 micrograms/ml). The degree of antimicrobial resistance found in Thailand is higher than that reported for H. ducreyi isolated in other regions. Five different outer membrane protein patterns were found by analyzing proteins in the range of 29 to 61 kilodaltons, but 98% of the Thai strains fell into three patterns which did not differ greatly. Outer membrane protein patterns of Thai strains were also seen in strains from other geographic areas. A new outer membrane protein type was found among nine strains isolated in Singapore.</jats:p

The impact of offspring and maternal obesogenic diets on adult offspring oocyte mitochondrial morphology in primordial and preantral follicles.

Diet-induced obesity reduces oocyte quality mainly by impacting oocyte mitochondrial functions. Moreover, maternal obesity is associated with mitochondrial dysfunction in oocytes of their adult offspring. However, these effects were reported only in fully grown oocytes, mainly in the form of abnormal mitochondrial ultrastructure. It is unknown if obesogenic (OB) diets or maternal obesity already impact the primordial and preantral follicles. Considering the long duration and dynamics of folliculogenesis, determining the stage at which oocytes are affected and the extent of the damage is crucial for optimal reproductive management of obese patients and their daughters. Potential interaction between maternal and offspring diet effects are also not described, yet pivotal in our contemporary society. Therefore, here we examined the impact of OB diets on oocyte mitochondrial ultrastructure in primordial and activated preantral follicles in offspring from diet-induced obese or lean mothers. We used an outbred Swiss mouse model to increase the pathophysiological relevance to humans. Female mice were fed control or OB diets for 7 weeks, then mated with control males. Their female offspring were fed control or OB diets after weaning for 7 weeks (2-by-2 factorial design). Adult offspring ovarian sections were examined using transmission electron microscopy. We characterised and classified unique features of oocyte mitochondrial ultrastructure in the preantral follicles. An increase in mitochondrial matrix density was the most predominant change during follicle activation in secondary follicles, a feature that is linked with a higher mitochondrial activity. Maternal obesity increased mitochondrial density already in the primordial follicles suggesting an earlier increase in bioenergetic capacity. Maternal obesity did not induce abberant ultrastructure (abnormalities and defects) in primordial or preantral follicles. In contrast, offspring OB diet increased mitochondrial abnormalities in the primordial follicles. Further investigation of the consequences of these changes on oocyte metabolic regulation and stress levels during folliculogenesis is needed

Maternal metabolic health and fertility : we should not only care about but also for the oocyte!

Metabolic disorders due to obesity and unhealthy lifestyle directly alter the oocyte's microenvironment and impact oocyte quality. Oxidative stress and mitochondrial dysfunction play key roles in the pathogenesis. Acute effects on the fully grown oocytes are evident, but early follicular stages are also sensitive to metabolic stress leading to a long-term impact on follicular cells and oocytes. Improving the preconception health is therefore of capital importance but research in animal models has demonstrated that oocyte quality is not fully recovered. In the in vitro fertilisation clinic, maternal metabolic disorders are linked with disappointing assisted reproductive technology results. Embryos derived from metabolically compromised oocytes exhibit persistently high intracellular stress levels due to weak cellular homeostatic mechanisms. The assisted reproductive technology procedures themselves form an extra burden for these defective embryos. Minimising cellular stress during culture using mitochondrial-targeted therapy could rescue compromised embryos in a bovine model. However, translating such applications to human in vitro fertilisation clinics is not simple. It is crucial to consider the sensitive epigenetic programming during early development. Research in humans and relevant animal models should result in preconception care interventions and in vitro strategies not only aiming at improving fertility but also safeguarding offspring health