A hydrogeochemical study was carried out on the shallow Catania Plain alluvial aquifer, in eastern Sicily to reconstruct its hydrogeological structure, the meteoric recharge and to assess the ...influence of human activities on groundwater. To characterize the geochemistry of the shallow aquifer, two sampling campaigns were carried out, August–October 2004 and April–May 2005 in 47 sites distributed throughout the plain. The samples were collected and analyzed for physical–chemical parameters and major ions, as well as stable isotopes (δ
18
O and δ
2
H). Alluvial deposits with heterogeneous grain sizes constitute the aquifer. Varying conditions of vertical and horizontal permeability lead to the presence of a multilayered aquifer with different conditions of confinement and partial interconnection among layers. The sampled waters were separated into four groups of different compositions due to the water–rock interaction with the different lithologies present in and around the study area. Maps of electrical conductivity and sulfate show a systematic control of land use, in correspondence with the biggest farms. High sulfate concentration is due to both the natural interaction between local meteoric waters and Etna’s plume and the mixing with groundwater coming from the area where evaporitic rocks of the Gessoso Solfifera formation are present. In addition, anthropogenic contamination cannot be ruled out. A rain gauge network, consisting of 3 sites located at different altitudes, was installed to collect rain waters to determine isotopic data (δ
2
H and δ
18
O) and to measure the monthly rainfall amount. Based on the isotopic composition of sampled waters, it has been established that beyond the direct meteoric recharge, the recharging areas are in the North (Mt. Etna) and the South (Hyblean Plateau).
The mechanism of action of praziquantel (PZQ), the drug of choice against schistosomiasis, is still unclear. Since exposure of schistosomes to the drug is associated with calcium influx and muscular ...contraction, calcium channels have been suggested as the target, although direct combination of PZQ with their subunits was never demonstrated. We report a hitherto unknown effect of PZQ, namely the inhibition of nucleoside uptake, as observed in living worms using radio-isotope labelled adenosine and uridine. This effect is clearly seen in schistosomes but is absent in mammalian cells in culture. Moreover it is a specific pharmacological effect seen exclusively with the active levo-R(-)stereo isomer of the drug, and is shared by at least one benzodiazepine having antischistosomal activity. This novel effect acquires significance given that schistosomes cannot synthesize purine nucleosides de novo. A possible relationship between this novel effect and the known action of PZQ on calcium channels is discussed, since adenosine is known to bind to specific receptors and to behave as an indirect antagonist of calcium release in mammalian cells. If calcium channels were correlated with adenosine receptors also in schistosomes, as they are in mammals, this would support the hypothesis that PZQ-induced calcium influx may be correlated to adenosine receptor blockade.
Praziquantel is the drug of choice for the treatment of all forms of schistosomiasis. This review summarizes the main features of the drug, with special attention being given to those aspects that ...may be of interest to the practicing physician. After a brief mention of the history, the chemistry, the major available brands and their costs, doses and administration schedules are reviewed. Pharmacokinetics and drug interactions are analyzed and the low toxicity and mild side effects are stressed. A major weakness of praziquantel is its relative inefficacy against recent infections, a factor that may occasionally result in low cure rates in hyperendemic areas. Recent findings of schistosome isolates with a decreased sensitivity to praziquantel are discussed in the broader context of a possible emergence of drug resistance.
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 possible.
The corpus compiled for the RIN ConDÉ project consists of twelve reference sources on Norman customary law, from the 13th to the 19th century. Despite dealing with the same subject, the texts in this ...corpus are very heterogeneous in terms of format and structure. The texts were processed with the HTR tool Transkribus; Python and XSLT languages were employed for automated transformations; lemmatization was performed by AnaLog and the data was encoded using the TEI encoding model. Processing the data required a stage of reflection to identify the best means of restoring the structures and reference systems and to devise a set of lemma and part-of-speech tags that would work for texts covering six centuries of linguistic evolution. To make the texts maxi - mally comparable, it was eventually decided to create a three-level structure (part > chapter > section).
The efficacy of praziquantel against a Puerto Rican strain of
Schistosoma mansoni was assessed using both in vivo and in vitro approach. The drug effective dose (50%) in the infected mouse model was ...about 30 times higher when determined against 28-day-old infections than against 7-week-old parasites. Single-sex female infections were also largely refractory to treatment and single-sex male infections moderately refractory, in comparison with bisexual infections. The in vitro approach consisted of overnight exposure of parasite cultures to various drug concentrations, followed by several days of culture in drug-free medium. In vitro results confirmed in vivo data and allowed for the observation of schistosome morphological phenomena after praziquantel exposure. Early worm contraction was observed in all cases, even after exposure to sub-lethal concentrations of praziquantel or upon exposure of the largely refractory 28-day-old schistosomes. In these instances, however, worms resumed movements and normal shape upon drug removal and were able to survive. The inference of these observations on the clinical use of praziquantel and on its mechanism of action is discussed.
The benzodiazepine Ro 11-3128 (methyl-clonazepam) presents several similarities with praziquantel with regard to its anti-schistosomal mode of action, since both drugs cause spastic paralysis, ...calcium influx and tegumental disruption in the parasites. In order to know whether the two compounds share the same binding sites in the schistosomes, we performed in vivo and in vitro competition experiments. We took advantage of the fact that Ro 11-3128 is active against immature Schistosoma mansoni (whereas praziquantel is inactive), and praziquantel is active against S. japonicum (which is insensitive to Ro 11-3128). An excess of praziquantel did not inhibit the activity of Ro 11-3128 against immature S. mansoni and an excess of Ro 11-3128 did not inhibit the activity of praziquantel against S. japonicum, suggesting that the schistosome binding sites of the two drugs are different. On the other hand, cytochalasin D, an agent known to perturb--among other things--calcium channel function, was capable of inhibiting the schistosomicidal activity of both praziquantel and Ro 11-3128, thus adding another element of similarity between the two anti-schistosomal agents. A similar, albeit partial, inhibition of the schistosomicidal activity of the two drugs was exerted by some of the classical calcium channel blockers. Taken together, these results suggest that praziquantel and Ro 11-3128, although binding to different schistosome receptor sites, may use the same basic anti-schistosomal effector mechanisms.
PDF
