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Barend M deC Bronsvoort Alfons Renz Virginia Tchakouté Vincent N Tanya David Ekale Alexander J Trees 《Filaria journal》2005,4(1):1-8
Background
Ivermectin (Mectizan?, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi.Methods
Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin (Ivomec®, Merck and Co. Inc.) at 500 μg/kg or doramectin (Dectamax®, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity.Results
There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels.Conclusion
These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. 相似文献3.
Reactive oxygen species (ROS) have been implicated in many pathologies, including sub- and infertility. Freeze/thawing of sperm samples is routinely performed in the cattle breeding industries in order to perform artificial insemination. This freeze/thaw procedure is known to induce ROS in sperm samples. Lipid peroxidation in fresh and frozen/thawed sperm cells was assessed by mass spectrometric analysis of the main endogenous phospholipid class, phosphatidylcholine, and by fluorescence techniques using the lipid peroxidation reporter probe C11-BODIPY(581/591). Peroxidation as reported by the fluorescent probe, clearly corresponded with the presence of hydroxy- and hydroperoxyphosphatidylcholine in the sperm membranes, which are early stage products of lipid peroxidation. This allowed us, for the first time, to correlate endogenous lipid peroxidation with localization of this process in living sperm cells. Lipid peroxidation was particularly strong in the midpiece and tail of frozen/thawed spermatozoa and significantly less intense in the head. Induction of peroxidation in fresh sperm cells with the lipid soluble ROS tert-butylhydroperoxide gave an even more pronounced effect, demonstrating antioxidant activity in the head of fresh sperm cells. Furthermore, we were able to show that spontaneous peroxidation was not a result of cell death, as only a pronounced subpopulation of living cells showed peroxidation after freeze/thawing. 相似文献
4.
van den Bos EJ Mees BM de Waard MC de Crom R Duncker DJ 《American journal of physiology. Heart and circulatory physiology》2005,289(3):H1291-H1300
Mouse myocardial infarction (MI) models are frequently used research tools. The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore, we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2- or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional shortening as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point, in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, cone-shaped infarcts with reperfusion at the macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice. 相似文献
5.
During bacterial protein synthesis, stalled ribosomes can be rescued by tmRNA, a molecule with both tRNA and mRNA features. The tRNA region of tmRNA has sequence similarity with tRNA(Ala) and also has a clover-leaf structure folded similarly as in canonical tRNAs. Here we propose the L-shape of tmRNA to be stabilized by two tertiary interactions between its D- and T-loop on the basis of phylogenetic and experimental evidence. Mutational analysis clearly demonstrates a tertiary interaction between G(13) and U(342). Strikingly, this in evolution conserved interaction is not primarily important for tmRNA alanylation and for binding to elongation factor Tu, but especially for a proper functioning of SmpB. 相似文献
6.
The pristine rain forest? Remnants of historical human impacts on current tree species composition and diversity 总被引:7,自引:0,他引:7
Barend S. van Gemerden Han Olff † Marc P.E. Parren Frans Bongers 《Journal of Biogeography》2003,30(9):1381-1390
Abstract Aim Tropical rain forests are often regarded as pristine and undisturbed by humans. In Central Africa, community‐wide disturbances by natural causes are rare and therefore current theory predicts that natural gap phase dynamics structure tree species composition and diversity. However, the dominant tree species in many African forests recruit poorly, despite the presence of gaps. To explain this, we studied the disturbance history of a species‐rich and structurally complex rain forest. Location Lowland rain forest in Southern Cameroon. Methods We identified the recruitment conditions of trees in different diameter classes in 16 ha of species‐rich and structurally complex ‘old growth’ rain forest. For the identification of recruitment preference we used independent data on the species composition along a disturbance gradient, ranging from shifting cultivation fields (representing large‐scale disturbance), to canopy gaps and old growth forest. Results In nine of sixteen 1‐ha forest plots the older trees preferred shifting cultivation fields for recruitment while younger trees preferred gaps and closed forest conditions. This indicates that these nine sites once experienced large‐scale disturbances. Three lines of evidence suggest that historical agricultural use is the most likely disturbance factor: (1) size of disturbed and undisturbed patches, (2) distribution of charcoal and (3) historical accounts of human population densities. Main conclusions Present‐day tree species composition of a structurally complex and species‐rich Central African rain forest still echoes historical disturbances, most probably caused by human land use between three to four centuries ago. Human impact on African rain forest is therefore, contrary to common belief, an issue not of the last decades only. Insights in historical use will help to get a more balanced view of the ‘pristine rain forest’, acknowledging that the dualism between ‘old growth’ and ‘secondary’ forest may be less clear than previously thought. 相似文献
7.
C Feuerstein R Peretti-Renucci M Savasta B Scatton M Manier A Dubois J Thibault N Mons M Geffard 《Analytical cellular pathology》1989,1(3):153-171
Major technical progress in the development of computer-based image analysis systems has made possible the entry of autoradiographic and immunohistochemical techniques into a new era where quantification via densitometry and morphometry has become easily accessible. In this context, quantitative biochemical data can be adapted to anatomical and histological resolution. This adaptation is most efficient in the neuroscience fields because of the huge importance of cellular communication via neuronal networks in the nervous system. Therefore, any experimental approach to the brain which considers the brain as a 'black box' appears now as very crude. In fact, subtle heterogeneity in the distribution of biochemical markers can now be demonstrated, as illustrated here by the use of quantitative autoradiography of D1 and D2 dopaminergic receptors in the striatum of the mammalian brain. Also, local adaptive changes resulting from chronic blockade of the dopaminergic input can be detected after repeated treatments with dopaminergic antagonists selective for D1 or D2 receptors or with surgical lesioning of the dopaminergic nigrostriatal pathway. The resulting plastic changes are unevenly distributed throughout the striatal target organ and vary according to the mode of suppressing the dopaminergic flow: direct destruction of the dopaminergic pathway or selective pharmacological manipulation without physical elimination of the dopaminergic cells themselves. All these results are discussed and reviewed in light of the most recent reports in this field. 相似文献
8.
Structural variation and functional importance of a D-loop-T-loop interaction in valine-accepting tRNA-like structures of plant viral RNAs 下载免费PDF全文
de Smit MH Gultyaev AP Hilge M Bink HH Barends S Kraal B Pleij CW 《Nucleic acids research》2002,30(19):4232-4240
Valine-accepting tRNA-like structures (TLSs) are found at the 3′ ends of the genomic RNAs of most plant viruses belonging to the genera Tymovirus, Furovirus, Pomovirus and Pecluvirus, and of one Tobamovirus species. Sequence alignment of these TLSs suggests the existence of a tertiary D-loop–T-loop interaction consisting of 2 bp, analogous to those in the elbow region of canonical tRNAs. The conserved G18·Ψ55 pair of regular tRNAs is found to covary in these TLSs between G·U (possibly also modified to G·Ψ) and A·G. We have mutated the relevant bases in turnip yellow mosaic virus (TYMV) and examined the mutants for symptom development on Chinese cabbage plants and for accumulation of genetic reversions. Development of symptoms is shown to rely on the presence of either A·G or G·U in the original mutants or in revertants. This finding supports the existence and functional importance of this tertiary interaction. The fact that only G·U and A·G are accepted at this position appears to result from steric and energetic limitations related to the highly compact nature of the elbow region. We discuss the implications of these findings for the various possible functions of the valine-accepting TLS. 相似文献
9.
Lina Gonzlez Gordon Paul R. Bessell Egbe F. Nkongho Victor N. Ngwa Vincent N. Tanya Melissa Sander Lucy Ndip Kenton L. Morgan Ian G. Handel Stella Mazeri Barend MdeC Bronsvoort Robert F. Kelly 《PLoS neglected tropical diseases》2022,16(3)
BackgroundCrimean-Congo Haemorrhagic Fever (CCHF) is a tick-borne viral zoonotic disease distributed across several continents and recognized as an ongoing health threat. In humans, the infection can progress to a severe disease with high fatality, raising public health concerns due to the limited prophylactic and therapeutic options available. Animal species, clinically unaffected by the virus, serve as viral reservoirs and amplifier hosts, and can be a valuable tool for surveillance. Little is known about the occurrence and prevalence of Crimean-Congo Haemorrhagic Fever Virus (CCHFV) in Cameroon. Knowledge on CCHFV exposure and the factors associated with its presence in sentinel species are a valuable resource to better understand transmission dynamics and assess local risks for zoonotic disease emergence.Methods and findingsWe conducted a CCHFV serological survey and risk factor analysis for animal level seropositivity in pastoral and dairy cattle in the North West Region (NWR) and the Vina Division (VD) of the Adamawa Region in Cameroon. Seroprevalence estimates were adjusted for sampling design-effects and test performance. In addition, explanatory multivariable logistic regression mixed-effects models were fit to estimate the effect of animal characteristics, husbandry practices, risk contacts and ecological features on the serological status of pastoral cattle. The overall seroprevalence was 56.0% (95% CI 53.5–58.6) and 6.7% (95% CI 2.6–16.1) among pastoral and dairy cattle, respectively. Animals going on transhumance had twice the odds of being seropositive (OR 2.0, 95% CI 1.1–3.8), indicating that animal movements could be implicated in disease expansion. From an ecological perspective, absolute humidity (OR 0.6, 95% CI 0.4–0.9) and shrub density (OR 2.1, 95% CI 1.4–3.2) were associated with seropositivity, which suggests an underlying viral dynamic connecting vertebrate host and ticks in a complex transmission network.ConclusionsThis study demonstrated high seroprevalence levels of CCHFV antibodies in cattle in Cameroon indicating a potential risk to human populations. However, current understanding of the underlying dynamics of CCHFV locally and the real risk for human populations is incomplete. Further studies designed using a One Health approach are required to improve local knowledge of the disease, host interactions and environmental risk factors. This information is crucial to better project the risks for human populations located in CCHFV-suitable ecological niches. 相似文献
10.
Wanda M. Admiraal Everlina M. Vlaar Vera Nierkens Frits Holleman Barend J. C. Middelkoop Karien Stronks Irene G. M. van Valkengoed 《PloS one》2013,8(7)