Blood calcium concentration and performance in periparturient and early lactating dairy cows is influenced by plant bioactive lipid compounds

Previous studies ex vivo suggested that plant bioactive lipid compounds (PBLC) can increase ruminal calcium absorption. Therefore, we hypothesized that PBLC feeding around calving may potentially counteract hypocalcemia and support performance in postpartum dairy cows. The corresponding aim of the study was to investigate the effect of PBLC feeding on blood minerals in Brown Swiss (BS) and hypocalcemia-susceptible Holstein Friesian (HF) cows during the period from d −2 to 28 relative to calving and on milk performance until d 80 of lactation. A total of 29 BS cows and 41 HF cows were divided each into a control (CON) and PBLC treatment group. The latter was supplemented with 1.7 g/d menthol-rich PBLC from 8 d before expected calving to 80 d postpartum. Milk yield and composition, body condition score and blood minerals were measured. Feeding PBLC induced a significant breed × treatment interaction for iCa, supporting that PBLC increased iCa exclusively in HF cows; the increase was 0.03 mM over the whole period and 0.05 mM from d 1 to 3 after calving. Subclinical hypocalcemia was seen in one BS-CON and 8 HF-CON cows and 2 BS-PBLC and 4 HF-PBLC cows. Clinical milk fever was detected only in HF cows (2 HF-CON and one HF-PBLC). Other tested blood minerals, such as sodium, chloride, and potassium, as well as blood glucose, were neither affected by PBLC feeding nor breed, nor were their 2-way interactions, except for higher sodium levels in PBLC cows on d 21. Body condition score showed no effect of treatment, except for a lower body condition score in BS-PBLC compared with BS-CON at d 14. Dietary PBLC increased milk yield, milk fat yield, and milk protein yield at 2 consecutive dairy herd improvement test days. As indicated by treatment × day interactions, energy-corrected milk yield and milk lactose yield were increased by PBLC on the first test day only, and milk protein concentration decreased from test d 1 to test d 2 in CON only. The concentrations of fat, lactose, and urea, as well as somatic cell count, were not affected by treatment. The weekly milk yield over the first 11 wk of lactation was 29.5 kg/wk higher for PBLC versus CON across breeds. It is concluded that the applied PBLC induced a small but measurable improvement of calcium status in HF cows in the study period and had additional positive effects on milk performance in both breeds

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni, Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy

<p>Abstract</p> <p>Background</p> <p>Miltefosine, which is the first oral drug licensed for the treatment of leishmaniasis, was recently reported to be a promising lead compound for the synthesis of novel antischistosomal derivatives with potent activity <it>in vivo </it>against different developmental stages of <it>Schistosoma mansoni</it>. In this paper an <it>in vitro </it>study was carried out to investigate whether it has a biocidal activity against the aquatic stages of <it>Schistosoma mansoni </it>and its snail intermediate host, <it>Biomphalaria alexandrina </it>, thus being also a molluscicide. Additionally, to see whether miltefosine can have a broad spectrum antischistosomal activity, a similar <it>in vitro </it>study was carried out on the adult stage of <it>Schistosoma haematobium</it>, the second major human species, its larval stages and snail intermediate host, <it>Bulinus truncutes</it>. This was checked by scanning electron microscopy.</p> <p>Results</p> <p>Miltefosine proved to have <it>in vitro </it>ovicidal, schistolarvicidal and lethal activity on adult worms of both <it>Schistosoma </it>species and has considerable molluscicidal activity on their snail hosts. Scanning electron microscopy revealed several morphological changes on the different stages of the parasite and on the soft body of the snail, which further strengthens the current evidence of miltefosine's activity. This is the first report of mollusicidal activity of miltefosine and its <it>in vitro </it>schistosomicidal activity against <it>S.haematobium</it>.</p> <p>Conclusions</p> <p>This study highlights miltefosine not only as a potential promising lead compound for the synthesis of novel broad spectrum schistosomicidal derivatives, but also for molluscicidals.</p

Anthelmintic activity of medicinal plants used in Côte d'Ivoire for treating parasitic diseases

Natural products play an important role in the discovery and development of new pharmaceuticals. In the present study, we assessed the anthelmintic properties of medicinal plants used in Cote d'Ivoire. Ethanolic extracts from 50 medicinal plants were tested in vitro against trematodes (Echinostoma caproni, Schistosoma mansoni) and nematodes (Ancylostoma ceylanicum, Heligmosomoides bakeri, Trichuris muris). Active extracts were evaluated for their cytotoxicity and followed up in vivo in mice harbouring adult S. mansoni, E. caproni and T. muris at single oral doses of 400 or 800 mg/kg. All extracts tested were active against at least one helminths species. Ten of the 65 extracts tested (15.4%) in vitro revealed activity against all helminths tested. Of 65 extracts tested in vitro at a concentration of 2 mg/ml, all caused death of schistosomula and 34.4% and 39.1% were lethal against adult S. mansoni and E. caproni 72 h post-incubation, respectively. The highest activity against A. ceylanicum in vitro was observed with Sclerocarya birrea at 2 mg/ml, which resulted in death of adult worms and inhibition of activity of third-stage larvae (L3). Of the extracts, 41.5% completely inhibited movement of H. bakeri L3 at minimal lethal concentration (MLC) values of 20-200 mug/ml 48 h post-incubation, and 15.4% paralysed adult H. bakeri at 200 mug/ml 72 h after incubation. Of the extracts, 19% resulted in death of adult T. muris at MLC values of 10-100 mug/ml. In vivo, none of the extracts tested revealed activity against E. caproni. Olax subscorpioidea achieved total and female worm burden reductions of 60% and 84%, respectively in S. mansoni-infected mice. Combretum mucronatum was the most active extracts in vivo against T. muris with a worm burden reduction of 85.3%. In conclusion, several of the medicinal plants used in Cote d'Ivoire are active against different helminths, hence might play a role in the treatment of helminthiases. Further studies are necessary to isol the active components from these extract