223 research outputs found
Black restoration is a black responsibility: Nigeria and the black leadership imperative
No full textEmerg Infect Dis
No full textControl of fecal-orally transmitted pathogens is inadequate in many developing countries, in particular, in sub-Saharan Africa. Acquired resistance to antimicrobial drugs is becoming more prevalent among Vibrio cholerae, Salmonella enteritidis, diarrheagenic Escherichia coli, and other pathogens in this region. The poor, who experience most of the infections caused by these organisms, bear the brunt of extended illness and exacerbated proportion of deaths brought about by resistance. Improved antimicrobial drug stewardship is an often cited, but inadequately implemented, intervention for resistance control. Resistance containment also requires improvements in infectious disease control, access to and quality assurance of antimicrobial agents, as well as diagnostic facilities. Structural improvements along these lines will also enhance disease prevention and control as well as rational antimicrobial drug use. Additionally, more research is needed to identify low-cost, high-impact interventions for resistance control
A study of the genetic basis of plasmid-borne antimicrobial resistance of uropathogenic Escherichia coli in Southwestern Nigeria
No full textNeospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294.
No full textBACKGROUND
Bumped kinase inhibitors (BKIs) are potential drugs for neosporosis treatment in farm animals. BKI-1294 exposure results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs, the re-emergence of viable tachyzoites following drug removal, and the localization of CDPK1, the molecular target of BKIs.
METHODS
N. caninum tachyzoites and MNCs were studied by TEM and immunofluorescence using antibodies directed against CDPK1, and against NcSAG1 and IMC1 as markers for tachyzoites and newly formed zoites, respectively.
RESULTS
After six days of drug exposure, MNCs lacked SAG1 surface expression but remained intracellular, and formed numerous zoites incapable of disjoining from each other. Following drug removal, proliferation continued, and zoites lacking NcSAG1 emerged from the periphery of these complexes, forming infective tachyzoites after 10 days. In intracellular tachyzoites, CDPK1 was evenly distributed but shifted towards the apical part once parasites were extracellular. This shift was not affected by BKI-1294.
CONCLUSIONS
CDPK1 has a dynamic distribution depending on whether parasites are located within a host cell or outside. During MNC-to-tachyzoite reconversion newly formed tachyzoites are generated directly from MNCs through zoites of unknown surface antigen composition. Further in vivo studies are needed to determine if MNCs could lead to a persistent reservoir of infection after BKI treatment
Vaccine-Linked Chemotherapy Approach: Additive Effects of Combining the Listeria monocytogenes-Based Vaccine Lm3Dx_NcSAG1 With the Bumped Kinase Inhibitor BKI-1748 Against Neospora caninum Infection in Mice.
No full textThe apicomplexan parasite Neospora (N.) caninum causes neosporosis in numerous host species. There is no marketed vaccine and no licensed drug for the prevention and/or treatment of neosporosis. Vaccine development against this parasite has encountered significant obstacles, probably due to pregnancy-induced immunomodulation hampering efficacy, which has stimulated the search for potential drug therapies that could be applied to limit the effects of neosporosis in dams as well as in offspring. We here investigated, in a pregnant neosporosis mouse model, the safety and efficacy of a combined vaccination-drug treatment approach. Mice were vaccinated intramuscularly with 1 × 107 CFU of our recently generated Listeria (L.) monocytogenes vaccine vector expressing the major N. caninum tachyzoite surface antigen NcSAG1 (Lm3Dx_SAG1). Following mating and experimental subcutaneous infection with 1 × 105 N. caninum (NcSpain-7) tachyzoites on day 7 of pregnancy, drug treatments were initiated using the bumped kinase inhibitor BKI-1748 at 20 mg/kg/day for 5 days. In parallel, other experimental groups were either just vaccinated or only treated. Dams and offspring were followed-up until day 25 post-partum, after which all mice were euthanized. None of the treatments induced adverse effects and neither of the treatments affected fertility or litter sizes. Cerebral infection in dams as assessed by real-time PCR was significantly reduced in the vaccinated and BKI-1748 treated groups, but was not reduced significantly in the group receiving the combination. However, in non-pregnant mice, all three treatment groups exhibited significantly reduced parasite burdens. Both, vaccination as well BKI-1748 as single treatment increased pup survival to 44 and 48%, respectively, while the combination treatment led to survival of 86% of all pups. Vertical transmission in the combination group was 23% compared to 46 and 50% in the groups receiving only BKI-treatment or the vaccine, respectively. In the dams, IgG titers were significantly reduced in all treatment groups compared to the untreated control, while in non-pregnant mice, IgG titers were reduced only in the group receiving the vaccine. Overall, vaccine-linked chemotherapy was more efficacious than vaccination or drug treatment alone and should be considered for further evaluation in a more relevant experimental model
PRICE REPORTING in A THIN MARKET
No full textCitation: Ajewole, K., Schroeder, T. C., & Parcell, J. (2016). PRICE REPORTING in A THIN MARKET. Journal of Agricultural and Applied Economics, 48(4), 345-365. doi:10.1017/aae.2016.19Thin markets create challenges for reporting market information by the U.S. Department of Agriculture (USDA) and for users of the information. This study examines distributions of transactions comprising daily price reports in the U.S. hog market. We determine publicly reported daily prices are sensitive to which packing plants buy hogs. Transaction prices comprising USDA Agricultural Marketing Service price reports are not normally distributed; care must be taken in reporting and interpreting transaction prices. Economically important variations in prices occur because of packer-specific indicators. Daily reported prices are used as base prices in marketing agreements, making variation of even greater importance. Copyright © The Author(s) 2016
Litter Mass and Nutrient Dynamics in a Transformed Rainforest Ecosystem in Southwestern Nigeria
No full textLitter mass and nutrient changes were studied in a tropical rainforest after the original vegetation was converted to a monoculture plantation of teak. (Tectona grandis Lim.) in Akure forest reserve in southwestern Nigeria. The amount of litter and macronutrients N, P, K, Ca and Mg in litterfall were determined and qualified. The difference in the mean annual litterfall of 6,688 kg ha-1 yr-1 and 3,774 kg ha-1 yr-1 for the natural forest and plantation respectively are in the ratio 2:1. The mean monthly litterfall was statistically significant at 5% probability level. Except for N, nutrient recycling from litterfall showed no significant difference between the two ecosystems. The relative content of the nutrient elements in the litterfall were in the order Ca>Mg>K>N>P in the plantation. Result showed that even though there was lot in litterfall as a result of the conversion, such was not enough to adversely affect the nutrient level of litter and overall litter nutrient contribution to the ecosystem. Key words: Teak; Litter mass; Macronutrients; Tropical rainforest DOI: 10.3329/bjsir.v45i4.7380 Bangladesh J. Sci. Ind. Res. 45(4), 351-358, 2010</jats:p
Treatment with BKI-1748 after Toxoplasma gondii systemic dissemination in experimentally infected pregnant sheep improves fetal and lamb mortality and morbidity and prevents congenital infection
No full textAuthor Contributions:
A.H., W.C.V.V., and L.M.O. were responsible for obtaining the funding for this study. R.S.S., I.F., A.H., W.C.V.V., and L.M.O. were involved in designing the study. R.S.S., M.R., and J.M.G. handled animal selection and carried out the breeding program. R.S.S., A.H.L., and A.L.T. were responsible for oocyst infection and drug administration. R.S.S., A.H.L., A.L.T., F.M.D., M.R., and J.M.G. participated in clinical examination of dams and lambs as well as in blood collection of the animals. R.S.S., A.H.L., A.L.T., and F.M.D. conducted necropsies and gathered post-mortem samples for molecular analysis. R.C., M.A.H., K.K.O., and S.L.M.A. evaluated the pharmacokinetic profile of the compound by analysing plasma samples and/or analyzing the results. R.S.S., A.H.L., and A.L.T. performed the study of the immune response and the molecular detection of the parasite. R.S.S., I.F., R.C., M.A.H., K.K.O., AH, WCVV and LMO wrote and/or edited the manuscript. All authors read and approved the final manuscript. Dr. Wesley C. Van Voorhis is the President and co-owner of ParaTheraTech Inc., a company that is developing BKIs for animal health. Dr. Van Voorhis did not perform the experiments, nor interpret the results of the experiments, but he did edit this paper and helped plan the experiments. The other authors declare that they have no competing interests.Drug development for congenital toxoplasmosis is challenging since first-line therapy has a high rate of adverse effects and exhibits suboptimal efficacy. Bumped kinase inhibitors (BKIs), targeting protein kinases with small gatekeeper residues, have been found to be effective against Toxoplasma gondii. The efficacy of BKI-1748 administered later than 2 days post-infection (p.i.), a scenario that may better reflect its real-world use as a therapeutic candidate, has not been investigated in T. gondii-infected pregnant sheep. For this purpose, 19 pregnant sheep were assigned to three experimental groups. Group 1 (G1, n = 8) and group 2 (G2, n = 8) were dosed orally with 10 TgShSp1 sporulated oocysts at 90 days of gestation (dg). Animals from group 3 (G3, n = 3) were simultaneously mock dosed with phosphate-buffered solution (PBS). In G1, BKI-1748 was administered orally from day 7 p.i. (fever and increased serum IFNγ levels) onward, maintaining drug exposure for 20 days (10 doses at 15 mg/kg every 2 days). Treated animals (G1) exhibited significantly lower rectal temperatures (on days 8 and 9 p.i.), serum IFNγ levels (on day 10 p.i.), and specific IgG levels when compared with non-treated animals (G2). At delivery, significantly higher percentages of healthy lambs were found in infected/treated sheep in G1 (73.3%) and in uninfected sheep in G3 (80%) compared with infected/untreated sheep in G2 (31.3%). Concerning congenital transmission, parasite DNA was neither detected in placenta nor target tissues (brain and lungs) from the fetuses/lambs in G1(infected/treated) and G3 (uninfected). By contrast, parasite DNA was detected in all placentas and lambs from G2 (infected/untreated), except for one sheep that aborted on day 13 p.i.Department of Agriculture (Estados Unidos)National Institutes of Health (Estados Unidos)Swiss National Science Foundation (Suiza)European CommissionDepto. de Sanidad AnimalFac. de VeterinariaTRUEpu
Staphylococcus sciuri gene erm(33), encoding inducible resistance to macrolides, lincosamides, and streptogramin B antibiotics, is a product of recombination between erm(C) and erm(A)
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