ABSTRACT
Groundwater in karst aquifers is frequently tapped for drinking purposes, due to frequent huge volumes of resources. Unfortunately, vulnerability of these aquifers can be high, due to possible fast transfer of recharge water on springs by the karst network. On Gran Sasso Mountain regional aquifer, several springs are subjected to drinking withdrawal and an updated evaluation of their potential is now a fundamental issue to be considered, facing climate change effects, which reflect on variation of discharge regimen and values. To distinguish between different contribution of spring recharge, a tracer test has been carried out on the Vitella d'Oro spring, fed both by the regional aquifer and by a local system exposed to karst features developed in the Rigopiano Conglomerates formation. Thanks to hydrogeological, hydrogeochemical and isotopic data, a conceptual model of spring recharge has been proposed and subsequently validated by the tracer test results. All information confirms the superimposition on the regional base flow, by a relevant contribution of the karst network, influencing the spring discharge in recharge periods. In detail, a fast flow component is responsible for discharge peaks and frequently of turbidity events, having a mean velocity ranging from 30 to 70 m/h in the aquifer. Besides of this fast flow, an additional aliquot of the recharge is due to the same local aquifer, but slower flow clearly identifiable by hydrochemistry and isotopic data. Thanks to these findings, a renewed management of the spring has been suggested, considering the different degrees of aquifer vulnerability (turbidity occurrence) directly related to the discharge regimen.
ABSTRACT
Gemcitabine (2',2'-difluoro-2'-deoxycytidine, or dFdC) is a promising anticancer agent with demonstrated clinical activity in solid tumours currently undergoing clinical trials. Despite extensive studies on the biochemical mechanism of action, cell cycle perturbations induced by dFdC have not yet been thoroughly investigated, apart from the expected inhibition of DNA synthesis. The aim of our study was to clarify whether cell population kinetics is a vital factor in the cytotoxicity of dFdC in single or repeated treatments and in the dFdC-cisplatin combination. Ovarian cancer cells growing in vitro were treated with dFdC for 1 hr in a range of concentrations from 10 nM to 10 microM. Cell kinetics was investigated by DNA-bromodeoxyuridine flow cytometry, using different experimental protocols to measure either the time course of DNA-synthesis inhibition or the fate of cells in G(1), S or G(2)M at the time of dFdC treatment or 24 hr later. A modified sulforhodamine B test was used to assess the growth inhibition caused by dFdC given alone or with cisplatin. Although dFdC promptly inhibited DNA synthesis, cytotoxicity on proliferating cells was not specific for cells initially in the S phase. DNA synthesis was restored after a G(1) block of variable, dose-dependent length, but recycling cells were intercepted at the subsequent checkpoints, resulting in delays in the G(2)M and G(1) phases. The activity of repeated treatment with dFdC + dFdC or dFdC + cisplatin was highly dependent on the interval length between them. These results suggest that the kinetics of cell recycling from a first dFdC treatment strongly affects the outcome of a second treatment with either dFdC itself or cisplatin.
