The homeostatic chemokine CCL21 predicts mortality in aortic stenosis patients and modulates left ventricular remodeling

BACKGROUND: CCL21 acting through CCR7, is termed a homeostatic chemokine. Based on its role in concerting immunological responses and its proposed involvement in tissue remodeling, we hypothesized that this chemokine could play a role in myocardial remodeling during left ventricular (LV) pressure overload. METHODS AND RESULTS: Our main findings were: (i) Serum levels of CCL21 were markedly raised in patients with symptomatic aortic stenosis (AS, n = 136) as compared with healthy controls (n = 20). (ii) A CCL21 level in the highest tertile was independently associated with all-cause mortality in these patients. (iii) Immunostaining suggested the presence of CCR7 on macrophages, endothelial cells and fibroblasts within calcified human aortic valves. (iv). Mice exposed to LV pressure overload showed enhanced myocardial expression of CCL21 and CCR7 mRNA, and increased CCL21 protein levels. (v) CCR7-/- mice subjected to three weeks of LV pressure overload had similar heart weights compared to wild type mice, but increased LV dilatation and reduced wall thickness. CONCLUSIONS: Our studies, combining experiments in clinical and experimental LV pressure overload, suggest that CCL21/CCR7 interactions might be involved in the response to pressure overload secondary to AS

Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases

The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, GBA and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural occurrence of 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and 13C6-labelled GlcChol as internal standard. In cells the inhibition of GBA increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol. Similarly, in GBA2-deficient mice GlcChol is reduced. Depletion of GlcCer by inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation reactions are highly dependent on local availability of suitable acceptors. In conclusion, mammalian tissues contain GlcChol formed by transglucosylation through β-glucosidases using GlcCer as donor. Our findings reveal a novel metabolic function for GlcCer.Bio-organic SynthesisMedical Biochemistr

Helminth eggs removal in water reclamation: disc filtration as an effective barrier

Increasing reuse of reclaimed water for unrestricted agricultural and landscape irrigation is raising considerable concern for human health protection due to the potential spread and contact with human parasites and pathogens. Parasites pose a significant public health concern and the removal of helminth eggs is becoming a crucial treatment step when providing safe reclaimed water. Although laboratory tests conducted so far indicate that microscreens can efficiently remove helminth eggs, convincing evidence was missing on the ability of full-scale processes to achieve such objective. This paper presents the results of a demonstration project conducted to validate the efficiency and the reliability of a gravity microscreening filtration process using the Hydrotech Discfilter, with a 10-μm pore size cloth, as a physical barrier for removing parasitic helminth eggs in full scale water reclamation plants. Tests were conducted at the Baix Llobregat Water Reclamation Plant in Barcelona (Spain) in May-June 2007. About 2 million helminth eggs of the Trichuris suis species were added to reclaimed water (7.6 m3 close recirculation system) and subsequently filtered through a Hydrotech Discfilter with 10-μm pore size cloth. A total of 68 samples of reclaimed water (34 influent samples of 20L, and 34 effluent samples of 100L) were analyzed using an adaptation of the Bailenger modified method, as recommended by WHO in “Wastewater analysis for agricultural use” by Ayres & Mara. Several changes to the modified method were applied at the Faculty of Pharmacy of the University of Barcelona, to improve the method recovery efficiency. Those adaptations resulted in an absolute recovery efficiency of up to 80-90%, considerably larger than the 30-74% recovery achieved by the recommended Bailenger modified method. Those recovery improvements were achieved by using a sample volume higher than that recommended, by omitting the grease extraction step, by analyzing total water sample volumes, and by counting all the helminth eggs present in a McMaster chamber. Results clearly showed that the Hydrotech Discfilter effluent had no helminth eggs, regardless of the helminth egg concentrations entering the filter (10–3200 eggs/20L), with the exception of one sample in which a 1egg/100L concentration was detected. Those results also confirm the high efficiency (up to 4.2 ulog for 100L samples) and reliability (3.5 ulog for 100L samples in 90% of the cases) of the parasitic helminth eggs retention process that takes places on the filter cloth. Those results illustrate the safety of the reclaimed water obtained, with parasitic helminth egg concentrations 10 times lower than the limit recommended by WHO guidelines (2006) and that established by the Spanish RD 1620/2007 (1 egg/10L). In summary, the Hydrotech Discfilter functions as an effective and reliable barrier against helminth eggs. Its small footprint, its low energy consumption and its simple operation and maintenance requirements make it a competitive and attractive technology for water reclamation and reuse. The full study report has been published by Veolia and is available at http://www.veoliawaterst.es.Peer ReviewedPostprint (published version

Helminth eggs removal in water reclamation: disc filtration as an effective barrier

Increasing reuse of reclaimed water for unrestricted agricultural and landscape irrigation is raising considerable concern for human health protection due to the potential spread and contact with human parasites and pathogens. Parasites pose a significant public health concern and the removal of helminth eggs is becoming a crucial treatment step when providing safe reclaimed water. Although laboratory tests conducted so far indicate that microscreens can efficiently remove helminth eggs, convincing evidence was missing on the ability of full-scale processes to achieve such objective. This paper presents the results of a demonstration project conducted to validate the efficiency and the reliability of a gravity microscreening filtration process using the Hydrotech Discfilter, with a 10-μm pore size cloth, as a physical barrier for removing parasitic helminth eggs in full scale water reclamation plants. Tests were conducted at the Baix Llobregat Water Reclamation Plant in Barcelona (Spain) in May-June 2007. About 2 million helminth eggs of the Trichuris suis species were added to reclaimed water (7.6 m3 close recirculation system) and subsequently filtered through a Hydrotech Discfilter with 10-μm pore size cloth. A total of 68 samples of reclaimed water (34 influent samples of 20L, and 34 effluent samples of 100L) were analyzed using an adaptation of the Bailenger modified method, as recommended by WHO in “Wastewater analysis for agricultural use” by Ayres & Mara. Several changes to the modified method were applied at the Faculty of Pharmacy of the University of Barcelona, to improve the method recovery efficiency. Those adaptations resulted in an absolute recovery efficiency of up to 80-90%, considerably larger than the 30-74% recovery achieved by the recommended Bailenger modified method. Those recovery improvements were achieved by using a sample volume higher than that recommended, by omitting the grease extraction step, by analyzing total water sample volumes, and by counting all the helminth eggs present in a McMaster chamber. Results clearly showed that the Hydrotech Discfilter effluent had no helminth eggs, regardless of the helminth egg concentrations entering the filter (10–3200 eggs/20L), with the exception of one sample in which a 1egg/100L concentration was detected. Those results also confirm the high efficiency (up to 4.2 ulog for 100L samples) and reliability (3.5 ulog for 100L samples in 90% of the cases) of the parasitic helminth eggs retention process that takes places on the filter cloth. Those results illustrate the safety of the reclaimed water obtained, with parasitic helminth egg concentrations 10 times lower than the limit recommended by WHO guidelines (2006) and that established by the Spanish RD 1620/2007 (1 egg/10L). In summary, the Hydrotech Discfilter functions as an effective and reliable barrier against helminth eggs. Its small footprint, its low energy consumption and its simple operation and maintenance requirements make it a competitive and attractive technology for water reclamation and reuse. The full study report has been published by Veolia and is available at http://www.veoliawaterst.es.Peer Reviewe

Helminth eggs removal in water reclamation: disc filtration as an effective barrier

Increasing reuse of reclaimed water for unrestricted agricultural and landscape irrigation is raising considerable concern for human health protection due to the potential spread and contact with human parasites and pathogens. Parasites pose a significant public health concern and the removal of helminth eggs is becoming a crucial treatment step when providing safe reclaimed water. Although laboratory tests conducted so far indicate that microscreens can efficiently remove helminth eggs, convincing evidence was missing on the ability of full-scale processes to achieve such objective. This paper presents the results of a demonstration project conducted to validate the efficiency and the reliability of a gravity microscreening filtration process using the Hydrotech Discfilter, with a 10-μm pore size cloth, as a physical barrier for removing parasitic helminth eggs in full scale water reclamation plants. Tests were conducted at the Baix Llobregat Water Reclamation Plant in Barcelona (Spain) in May-June 2007. About 2 million helminth eggs of the Trichuris suis species were added to reclaimed water (7.6 m3 close recirculation system) and subsequently filtered through a Hydrotech Discfilter with 10-μm pore size cloth. A total of 68 samples of reclaimed water (34 influent samples of 20L, and 34 effluent samples of 100L) were analyzed using an adaptation of the Bailenger modified method, as recommended by WHO in “Wastewater analysis for agricultural use” by Ayres & Mara. Several changes to the modified method were applied at the Faculty of Pharmacy of the University of Barcelona, to improve the method recovery efficiency. Those adaptations resulted in an absolute recovery efficiency of up to 80-90%, considerably larger than the 30-74% recovery achieved by the recommended Bailenger modified method. Those recovery improvements were achieved by using a sample volume higher than that recommended, by omitting the grease extraction step, by analyzing total water sample volumes, and by counting all the helminth eggs present in a McMaster chamber. Results clearly showed that the Hydrotech Discfilter effluent had no helminth eggs, regardless of the helminth egg concentrations entering the filter (10–3200 eggs/20L), with the exception of one sample in which a 1egg/100L concentration was detected. Those results also confirm the high efficiency (up to 4.2 ulog for 100L samples) and reliability (3.5 ulog for 100L samples in 90% of the cases) of the parasitic helminth eggs retention process that takes places on the filter cloth. Those results illustrate the safety of the reclaimed water obtained, with parasitic helminth egg concentrations 10 times lower than the limit recommended by WHO guidelines (2006) and that established by the Spanish RD 1620/2007 (1 egg/10L). In summary, the Hydrotech Discfilter functions as an effective and reliable barrier against helminth eggs. Its small footprint, its low energy consumption and its simple operation and maintenance requirements make it a competitive and attractive technology for water reclamation and reuse. The full study report has been published by Veolia and is available at http://www.veoliawaterst.es.Peer Reviewe