Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

Long-term optical variability of PKS 2155-304

Aims: The optical variability of the blazar PKS 2155-304 is investigated to characterise the red noise behaviour at largely different time scales from 20 days to O(>10 yrs). Methods: The long-term optical light curve of PKS 2155-304 is assembled from archival data as well as from so-far unpublished observations mostly carried out with the ROTSE-III and the ASAS robotic telescopes. A forward folding technique is used to determine the best-fit parameters for a model of a power law with a break in the power spectral density function (PSD). The best-fit parameters are estimated using a maximum-likelihood method with simulated light curves in conjunction with the Lomb Scargle Periodogram (LSP) and the first-order Structure Function (SF). In addition, a new approach based upon the so-called Multiple Fragments Variance Function (MFVF) is introduced and compared to the other methods. Simulated light curves have been used to confirm the reliability of these methods as well as to estimate the uncertainties of the best-fit parameters. Results: The light curve is consistent with the assumed broken power-law PSD. All three methods agree within the estimated uncertainties with the MFVF providing the most accurate results. The red-noise behaviour of the PSD in frequency f follows a power law with f^-{\beta}, {\beta}=1.8 +0.1/-0.2 and a break towards f^0 at frequencies lower than f_min=(2.7 +2.2/-1.6 yrs)^-1.Comment: 10 pages, 8 figures, the ROTSE-light curve can be downloaded from http://vizier.cfa.harvard.edu/viz-bin/VizieR?-source=J/A+A/531/A12

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Catching the radio flare in CTA 102 I. Light curve analysis

Context: The blazar CTA 102 (z=1.037) underwent a historical radio outburst in April 2006. This event offered a unique chance to study the physical properties of the jet. Aims: We used multifrequency radio and mm observations to analyze the evolution of the spectral parameters during the flare as a test of the shock-in-jet model under these extreme conditions. Methods: For the analysis of the flare we took into account that the flaring spectrum is superimposed on a quiescent spectrum. We reconstructed the latter from archival data and fitted a synchrotron self-absorbed distribution of emission. The uncertainties of the derived spectral parameters were calculated using Monte Carlo simulations. The spectral evolution is modeled by the shock-in-jet model, and the derived results are discussed in the context of a geometrical model (varying viewing angle) and shock-shock interaction. Results: The evolution of the flare in the turnover frequency-turnover flux density plane shows a double peak structure. The nature of this evolution is dicussed in the frame of shock-in-jet models. We discard the generation of the double peak structure in the turnover frequency-turnover flux density plane purely based on geometrical changes (variation of the Doppler factor). The detailed modeling of the spectral evolution favors a shock-shock interaction as a possible physical mechanism behind the deviations from the standard shock-in-jet model.Comment: 15 pages, 12 figure

Assessment of kinetic model for ceria oxidation for chemical-looping CO2 dissociation

Chemical looping technologies are identified as to have an excellent potential for CO2 capture and fuels synthesis. Oxygen carriers are the fundamental component of a chemical looping process, and the choice of stable and efficient carriers with fast redox kinetics is the key to the successful design of the process. Hence, understanding the reaction kinetics is of paramount importance for the selection of an appropriate oxygen carrier material. This work provides a method for kinetic model selection based on a statistical approach to identify the reaction mechanism. The study experimentally investigates the oxidation kinetics of CeO2-d by CO2 and applies a statistical method for the selection of the best-fitting kinetic model for the reaction. The kinetic study is performed in the temperature range of 700–1000¿°C with a CO2 concentration between 20 and 40¿vol% in the feed. The measured peak rates of CO production on ceria were influenced both by temperature and concentration of reactant. The total CO production was more influenced by the temperature than by CO2 concentration, with a maximum CO yield of 33.66¿ml/g at 1000¿°C and 40% CO2. The identification of the oxidation kinetic model is performed by fitting different reactions models to the measured reaction rates and statistically comparing them using the Residual sum of squares (RSS), Akaike information criterion (AICc) and the F-test for the selection of the best-fitting one. Models corresponding to the nucleation and grain growth reaction mechanism provided a good fit of the data, with the Sestak-Berggren (SB) model showing the best approximation of the measured rate of reaction with an evaluated activation energy of 79.1¿±¿6.5¿kJ/mol for the CO2 oxidation.Peer ReviewedPostprint (author's final draft

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

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

Optical and radio variability of the BL Lac object AO 0235+16: a possible 5-6 year periodicity

New optical and radio data on the BL Lacertae object AO 0235+16 have been collected in the last four years by a wide international collaboration, which confirm the intense activity of this source. The optical data also include the results of the Whole Earth Blazar Telescope (WEBT) first-light campaign organized in November 1997. The optical spectrum is observed to basically steepen when the source gets fainter. We have investigated the existence of typical variability time scales and of possible correlations between the optical and radio emissions by means of visual inspection, Discrete Correlation Function analysis, and Discrete Fourier Transform technique. The major radio outbursts are found to repeat quasi-regularly with a periodicity of about 5.7 years; this period is also in agreement with the occurrence of some of the major optical outbursts, but not all of them.Comment: to be published in A&