Quantifying the drivers of the increasing colored organic matter in boreal surface waters.

Long-term monitoring of surface water quality has shown increasing concentrations of colored dissolved organic matter (CDOM) across large parts of the northern latitudes. This has increased purification costs for domestic water works. Appropriate abatement actions require better knowledge of the governing factors for the increase, and this has motivated a growing scientific interest in understanding the factors and mechanisms promoting the CDOM increase. A proposed water color model for an important raw water source for Oslo, Norway, is based on the precipitation's amount and mobile ion concentration. The model explained more than 93% of the temporal variation in CDOM between 1983 and 2008. The model structure was also tested on three adjacent raw water sources and was found to explain 75-82% of the CDOM development throughout the same period. The long-term trend of increasing CDOM was closely related to the decline in sulfate and chloride concentrations in precipitation. Furthermore, interannual fluctuations in CDOM were explained by variation in predominant water flow paths, depending on amounts and intensity of precipitation, both of which are predicted to increase in several parts of the northern latitudes according to climate change scenarios.

Drug-induced lysosomal storage of sulfated glycosaminoglycans. Studies on the underlying structure-activity relationships.

Some immunomodulatory drugs have previously been shown to induce lysosomal storage of sulfated glycosaminoglycans (sGAG) in intact organisms and cultured cells. These compounds consist of a planary aromatic ring system and two symmetric side chains each carrying a protonizable nitrogen. The purpose of this study was to test a larger collection of such compounds for their potencies to induce lysosomal storage of sGAG in cultured fibroblasts of rat cornea. The cells were exposed (72 h) to various compounds differing with respect to the aromatic ring system or the side chains. Lysosomal sGAG-storage was demonstrated by selective cytochemical staining with cuprolinic blue. The threshold concentration, i.e., the concentration necessary to induce cuprolinic blue-positive cytoplasmic inclusions in at least 1% of the cells, was determined for each compound. The threshold concentrations were distributed over a range of 0.3-30 microM. It should be emphasized that the threshold concentration of a given compound is not a constant, but depends on the volume of cell culture medium per surface area of cell monolayer, since the lysosomal accumulation lowers the initial drug concentration in the medium. If the ratio of medium volume:cell monolayer surface is increased as compared with standard cell culture conditions, the threshold concentration will be lowered. The compounds were ranked according to their threshold concentrations as determined under standard conditions. The following conclusions can be drawn from the ranking: the type of the central aromatic ring system and the distance between the ring system and the protonizable nitrogen atoms of the side chains influence the potency to induce lysosomal sGAG-storage. Regarding the ring system, the potency decreases as follows: acridine approximately anthrachinone > fenfluorenone approximately fenfluorene > xanthenone; xanthene > dibenzofuran approximately dibenzothiophene. In intact organisms, these structure-activity relationships may be superimposed by drug metabolism and pharmacokinetic factors.

Lysosomal storage of sulfated glycosaminoglycans in cultured fibroblasts exposed to immunostimulatory acridine derivatives.

The purpose of the present cytological and radiochemical study was to investigate whether the immunomodulatory agent 3,6-bis[2-(diethylamino)ethoxy]acridine (CL-90.100) and three congeners induce lysosomal storage of sulfated glycosaminoglycans (sGAG) in cultured rat corneal fibroblasts. The reason for asking this question was as follows: The four acridine derivatives have molecular similarities with the dicationic amphiphilic compound tilorone, which has previously been shown to cause sGAG storage in cultured cells and in intact rats. The cells were exposed to the drugs for 72 hr. Tilorone served as reference. All acridine derivatives caused cytological alterations which, on the basis of the cytochemical results, were indicative of lysosomal sGAG storage. The threshold concentrations ranged from 0.3 to 0.7 microM. Radiochemical experiments showed that CL-90.100 up to 10 microM induced [35S]GAG storage in a dose-dependent manner, with an EC50 of 2 microM. Concentrations above 10 microM were cytotoxic. Experiments with equimolar concentrations (3 microM) demonstrated that three of the acridine derivatives were more potent and one was less potent than tilorone. Additionally, CL-90.100 was tested on bovine corneal fibroblasts, with cytochemical and radiochemical results similar to those in rat cells. The present findings show that (a) the four acridine derivatives induce lysosomal sGAG storage; (b) the acridine ring, compared with the fenfluorenone ring (tilorone), enhances this potency; and (c) the substituents at the nitrogens can have some influence on the potency to induce sGAG storage.