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Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?
Bruno Levecke ,Nathalie De Wilde,Els Vandenhoute,Jozef Vercruysse
PLOS Neglected Tropical Diseases , 2009, DOI: 10.1371/journal.pntd.0000366
Abstract: Background Soil-transmitted helminths, such as Trichuris trichiura, are of major concern in public health. Current efforts to control these helminth infections involve periodic mass treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring the drug efficacy will become indispensible. However, studies comparing detection techniques based on sensitivity, fecal egg counts (FEC), feasibility for mass diagnosis and drug efficacy estimates are scarce. Methodology/Principal Findings In the present study, the ether-based concentration, the Parasep Solvent Free (SF), the McMaster and the FLOTAC techniques were compared based on both validity and feasibility for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In addition, the drug efficacy estimates of quantitative techniques was examined using a statistical simulation. Trichuris eggs were found in 47% of the samples. FLOTAC was the most sensitive technique (100%), followed by the Parasep SF (83.0% [95% confidence interval (CI): 82.4–83.6%]) and the ether-based concentration technique (76.6% [95% CI: 75.8–77.3%]). McMaster was the least sensitive (61.7% [95% CI: 60.7–62.6%]) and failed to detect low FEC. The quantitative comparison revealed a positive correlation between the four techniques (Rs = 0.85–0.93; p<0.0001). However, the ether-based concentration technique and the Parasep SF detected significantly fewer eggs than both the McMaster and the FLOTAC (p<0.0083). Overall, the McMaster was the most feasible technique (3.9 min/sample for preparing, reading and cleaning of the apparatus), followed by the ether-based concentration technique (7.7 min/sample) and the FLOTAC (9.8 min/sample). Parasep SF was the least feasible (17.7 min/sample). The simulation revealed that the sensitivity is less important for monitoring drug efficacy and that both FLOTAC and McMaster were reliable estimators. Conclusions/Significance The results of this study demonstrated that McMaster is a promising technique when making use of FEC to monitor drug efficacy in Trichuris.
Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
Bruno Levecke ,Niko Speybroeck,Robert J. Dobson,Jozef Vercruysse,Johannes Charlier
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001427
Abstract: Background The fecal egg count reduction test (FECRT) is recommended to monitor drug efficacy against soil-transmitted helminths (STHs) in public health. However, the impact of factors inherent to study design (sample size and detection limit of the fecal egg count (FEC) method) and host-parasite interactions (mean baseline FEC and aggregation of FEC across host population) on the reliability of FECRT is poorly understood. Methodology/Principal Findings A simulation study was performed in which FECRT was assessed under varying conditions of the aforementioned factors. Classification trees were built to explore critical values for these factors required to obtain conclusive FECRT results. The outcome of this analysis was subsequently validated on five efficacy trials across Africa, Asia, and Latin America. Unsatisfactory (<85.0%) sensitivity and specificity results to detect reduced efficacy were found if sample sizes were small (<10) or if sample sizes were moderate (10–49) combined with highly aggregated FEC (k<0.25). FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The most discriminatory study design required 200 subjects independent of STH status (including subjects who are not excreting eggs). For this sample size, the detection limit of the FEC method and the level of aggregation of the FEC did not affect the interpretation of the FECRT. Only for a threshold of 90%, mean baseline FEC <150 eggs per gram of stool led to a reduced discriminatory power. Conclusions/Significance This study confirms that the interpretation of FECRT is affected by a complex interplay of factors inherent to both study design and host-parasite interactions. The results also highlight that revision of the current World Health Organization guidelines to monitor drug efficacy is indicated. We, therefore, propose novel guidelines to support future monitoring programs.
Integrating Fasciolosis Control in the Dry Cow Management: The Effect of Closantel Treatment on Milk Production
Johannes Charlier, Miel Hostens, Jos Jacobs, Bonny Van Ranst, Luc Duchateau, Jozef Vercruysse
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043216
Abstract: The liver fluke Fasciola hepatica is a parasite of ruminants with a worldwide distribution and an apparent increasing incidence in EU member states. Effective control in dairy cattle is hampered by the lack of flukicides with a zero-withdrawal time for milk, leaving the dry period as the only time that preventive treatment can be applied. Here, we present the results of a blinded, randomized and placebo-controlled trial on 11 dairy herds (402 animals) exposed to F. hepatica to 1) assess the effect of closantel treatment at dry-off (or 80–42 days before calving in first-calving heifers) on milk production parameters and 2) evaluate if a number of easy-to-use animal parameters is related to the milk production response after treatment. Closantel treatment resulted in a noticeable decrease of anti-F. hepatica antibody levels from 3–6 months after treatment onwards, a higher peak production (1.06 kg) and a slightly higher persistence (9%) of the lactation, resulting in a 305-day milk production increase of 303 kg. No effects of anthelmintic treatment were found on the average protein and fat content of the milk. Milk production responses after treatment were poor in meagre animals and clinically relevant higher milk production responses were observed in first-lactation animals and in cows with a high (0.3–0.5 optical density ratio (ODR)), but not a very high (≥0.5 ODR) F. hepatica ELISA result on a milk sample from the previous lactation. We conclude that in dairy herds exposed to F. hepatica, flukicide treatment at dry-off is a useful strategy to reduce levels of exposure and increase milk production in the subsequent lactation. Moreover, the results suggest that treatment approaches that only target selected animals within a herd can be developed based on easy-to-use parameters.
Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile
Prisca R Hoorens, Manuela Rinaldi, Robert W Li, Bruno Goddeeris, Edwin Claerebout, Jozef Vercruysse, Peter Geldhof
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-140
Abstract: Nine bovine membrane-associated mucins (MUC1, MUC3A, MUC4, MUC12, MUC13, MUC15, MUC16, MUC20 and MUC21) and six secreted mucins (MUC2, MUC5AC, MUC5B, MUC6, MUC7 and MUC19) were identified in the bovine genome. No homologues could be identified for MUC3B, MUC8 and MUC17. In general, domain architecture of the membrane-associated mucins was found to be similar between humans and cattle, while the protein architecture of the gel-forming mucins appeared to be less conserved. Further analysis of the genomic organization indicated that the previously reported bovine submaxillary mucin (BSM) may be part of a larger gene encoding for MUC19. Analysis of the transcription profile showed that the secreted mucins were transcribed from the abomasum onwards, whereas the membrane associated mucins MUC1 and MUC20 were transcribed throughout the whole GI tract. In contrast to humans, MUC5B transcript was found in both the small and large intestine, but was absent in oesophageal tissue.This study provides the first characterization of the mucin gene family in cattle and their transcriptional regulation in the GI tract. The data presented in this paper will allow further studies of these proteins in the physiology of the GI tract in ruminants and their interactions with pathogens.Mucins (MUC) are heavily O-glycosylated proteins that cover all mucosal surfaces. They play an important protective role as they form a physical, chemical and immunological barrier between the environment and the organism. Mucins can be largely divided into 2 structurally different families: the secreted and the membrane (cell surface)-associated mucins [1-4]. In humans, 7 members in the family of the secreted mucins have been identified, which can be further subdivided into gel-forming mucins (MUC2, MUC5AC, MUC5B, MUC6, MUC19) and non-gel-forming mucins (MUC7, MUC8) [5-7]. The membrane-associated mucins, on the other hand, count 11 members (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC13, MUC15, MUC16, MUC17, MUC20 a
Comparison of Individual and Pooled Stool Samples for the Assessment of Soil-Transmitted Helminth Infection Intensity and Drug Efficacy
Zeleke Mekonnen,Selima Meka,Mio Ayana,Johannes Bogers,Jozef Vercruysse,Bruno Levecke
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002189
Abstract: Background In veterinary parasitology samples are often pooled for a rapid assessment of infection intensity and drug efficacy. Currently, studies evaluating this strategy in large-scale drug administration programs to control human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm), are absent. Therefore, we developed and evaluated a pooling strategy to assess intensity of STH infections and drug efficacy. Methods/Principal Findings Stool samples from 840 children attending 14 primary schools in Jimma, Ethiopia were pooled (pool sizes of 10, 20, and 60) to evaluate the infection intensity of STHs. In addition, the efficacy of a single dose of mebendazole (500 mg) in terms of fecal egg count reduction (FECR; synonym of egg reduction rate) was evaluated in 600 children from two of these schools. Individual and pooled samples were examined with the McMaster egg counting method. For each of the three STHs, we found a significant positive correlation between mean fecal egg counts (FECs) of individual stool samples and FEC of pooled stool samples, ranging from 0.62 to 0.98. Only for A. lumbricoides was any significant difference in mean FEC of the individual and pooled samples found. For this STH species, pools of 60 samples resulted in significantly higher FECs. FECR for the different number of samples pooled was comparable in all pool sizes, except for hookworm. For this parasite, pools of 10 and 60 samples provided significantly higher FECR results. Conclusion/Significance This study highlights that pooling stool samples holds promise as a strategy for rapidly assessing infection intensity and efficacy of administered drugs in programs to control human STHs. However, further research is required to determine when and how pooling of stool samples can be cost-effectively applied along a control program, and to verify whether this approach is also applicable to other NTDs.
A Role for Eosinophils in the Intestinal Immunity against Infective Ascaris suum Larvae
Dries Masure,Johnny Vlaminck,Tao Wang,Koen Chiers,Wim Van den Broeck,Jozef Vercruysse,Peter Geldhof
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002138
Abstract: The aim of this study was to explore the mechanisms of resistance against invading Ascaris suum larvae in pigs. Pigs received a low dose of 100 A. suum eggs daily for 14 weeks. This resulted in a >99% reduction in the number of larvae that could migrate through the host after a challenge infection of 5000 A. suum eggs, compared to na?ve pigs. Histological analysis at the site of parasite entry, i.e. the caecum, identified eosinophilia, mastocytosis and goblet cell hyperplasia. Increased local transcription levels of genes for IL5, IL13, eosinophil peroxidase and eotaxin further supported the observed eosinophil influx. Further analysis showed that eosinophils degranulated in vitro in response to contact with infective Ascaris larvae in the presence of serum from both immune and na?ve animals. This effect was diminished with heat-inactivated serum, indicating a complement dependent mechanism. Furthermore, eosinophils were efficient in killing the larvae in vitro when incubated together with serum from immune animals, suggesting that A. suum specific antibodies are required for efficient elimination of the larvae. Together, these results indicate an important role for eosinophils in the intestinal defense against invading A. suum larvae.
The Intestinal Expulsion of the Roundworm Ascaris suum Is Associated with Eosinophils, Intra-Epithelial T Cells and Decreased Intestinal Transit Time
Dries Masure,Tao Wang,Johnny Vlaminck,Sarah Claerhoudt,Koen Chiers,Wim Van den Broeck,Jimmy Saunders,Jozef Vercruysse,Peter Geldhof
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002588
Abstract: Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections.
Equivalences between categories of modules and categories of comodules
Joost Vercruysse
Mathematics , 2006,
Abstract: We show the close connection between appearingly different Galois theories for comodules introduced recently in [J. G\'omez-Torrecillas and J. Vercruysse, Comatrix corings and Galois Comodules over firm rings, arXiv:math.RA/0509106.] and [R. Wisbauer, On Galois comodules (2004), to appear in Comm. Algebra.]. Furthermore we study equivalences between categories of comodules over a coring and modules over a firm ring. We show that these equivalences are related to Galois theory for comodules.
Quasi-co-Frobenius corings as Galois comodules
Joost Vercruysse
Mathematics , 2008,
Abstract: We compare several quasi-Frobenius-type properties for corings that appeared recently in literature and provide several new characterizations for each of these properties. By applying the theory of Galois comodules with a firm coinvariant ring, we can characterize a locally quasi-Frobenius (quasi-co-Frobenius) coring as a locally projective generator in its category of comodules.
Hopf algebras---Variant notions and reconstruction theorems
Joost Vercruysse
Mathematics , 2012,
Abstract: Hopf algebras are closely related to monoidal categories. More precise, $k$-Hopf algebras can be characterized as those algebras whose category of finite dimensional representations is an autonomous monoidal category such that the forgetful functor to $k$-vectorspaces is a strict monoidal functor. This result is known as the Tannaka reconstruction theorem (for Hopf algebras). Because of the importance of both Hopf algebras in various fields, over the last last few decades, many generalizations have been defined. We will survey these different generalizations from the point of view of the Tannaka reconstruction theorem.
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