The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function

Tetracycline antibiotics act by inhibiting bacterial protein translation. Given the bacterial ancestry of mitochondria, we tested the hypothesis that doxycycline—which belongs to the tetracycline class—reduces mitochondrial function, and results in cardiac contractile dysfunction in cultured H9C2 cardiomyoblasts, adult rat cardiomyocytes, in Drosophila and in mice. Ampicillin and carbenicillin were used as control antibiotics since these do not interfere with mitochondrial translation. In line with its specific inhibitory effect on mitochondrial translation, doxycycline caused a mitonuclear protein imbalance in doxycycline-treated H9C2 cells, reduced maximal mitochondrial respiration, particularly with complex I substrates, and mitochondria appeared fragmented. Flux measurements using stable isotope tracers showed a shift away from OXPHOS towards glycolysis after doxycycline exposure. Cardiac contractility measurements in adult cardiomyocytes and Drosophila melanogaster hearts showed an increased diastolic calcium concentration, and a higher arrhythmicity index. Systolic and diastolic dysfunction were observed after exposure to doxycycline. Mice treated with doxycycline showed mitochondrial complex I dysfunction, reduced OXPHOS capacity and impaired diastolic function. Doxycycline exacerbated diastolic dysfunction and reduced ejection fraction in a diabetes mouse model vulnerable for metabolic derangements. We therefore conclude that doxycycline impairs mitochondrial function and causes cardiac dysfunction.     

Advances in on-line drinking water quality monitoring and early warning systems

Significant advances have been made in recent years in technologies to monitor drinking water quality for source water protection, treatment operations, and distribution system management, in the event of accidental (or deliberate) contamination. Reports prepared through the Global Water Research Coalition (GWRC) and United States Environment Protection Agency (USEPA) agree that while many emerging technologies show promise, they are still some years from being deployed on a large scale. Further underpinning their viability is a need to interpret data in real time and implement a management strategy in response. This review presents the findings of an international study into the state of the art in this field. These results are based on visits to leading water utilities, research organisations and technology providers throughout Europe, the United States and Singapore involved in the development and deployment of on-line monitoring technology for the detection of contaminants in water.     

UV/H2O2 Treatment: A Practical Solution for Organic Contaminant Control and Primary Disinfection

PWN's water treatment plant Andijk was commissioned almost 40 years ago. It services water from the IJssel Lake by conventional surface water treatment. In view of taste and odor problems the plant was retrofitted with GAC filtration 25 years ago. The finished water quality still complies with all E.C. and Dutch drinking water standards. Nevertheless an upgrade is desired to avoid the use of chlorine and to extend the barriers against pathogenic micro-organisms and a broad range of organic micropollutants such as pesticides, rocket fuel by-products (NDMA), fuel oxygenates (MTBE), solvents (dioxane), endocrine disruptors, algae toxins, pharmaceuticals, etc. UV/H₂O₂ treatment was selected for both primary disinfection and organic contaminant control. The disinfection requirements were based on a 10^?4 health risk. The required 3 log inactivation for Giardia and Cryptosporidium was achieved by an UV dose lower than 20 mJ/cm². The highest UV dose, 105 mJ/cm², was needed for the inactivation of spores of Sulphite Reducing Clostridia. Reactivation of protozoa was established for UV doses up to 25 mJ/cm², for doses higher than 45 mJ/cm² no reactivation was observed. In view of the raw water concentrations the required organic contaminant degradation was set at 80%. Collimated beam and pilot-plant work showed that the required degradation can be achieved by the proper combination of electric energy and H₂O₂. In a UV reactor optimized for organic contaminant control, UV dose of 540 mJ/cm² (about 0.5 kWh/m³) and 6 mg/L H₂O₂ were needed. Under those conditions pesticides (atrazine), NDMA, MTBE, dioxane, endocrine disruptors (bisphenol A), microcystine and pharmaceuticals (diclofenac, ibuprofen) could be removed up to the required 80%. Bromate formation was absent while formation of primary metabolites was insignificant. The UV dose for organic contaminant control is about five times higher than the dose needed for disinfection. The UV/H₂O₂ process was implemented into the existing treatment train between the sand and GAC filters. In the GAC filters excess H₂O₂ is degraded, nitrite is converted into nitrate and biodegradable reaction products are consumed by bacteria. The full-scale installation with 3 streets of 4 Trojan Swift 16L30 reactors has been in operation since October 2004. Disinfection and organic contaminant control are as expected.     

Inhibitory effects of drinker and nondrinker prototypes on adolescent alcohol consumption.

This prospective study examined the relation between 308 adolescents' images of typical drinkers and nondrinkers and their subsequent alcohol consumption. The results indicate that both images are associated with changes in consumption between ages 16 and 18 but that they operate in different ways. Contrary to previous assumptions, drinker images do not represent goal states for adolescents in that they are more negative than their self-images and nondrinker images and are not correlated with their ideal selves. In contrast, nondrinker images do appear to represent goal states for adolescents who abstain from drinking. Implications for intervention are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enzymatic versus nonenzymatic conversions during the reduction of EDTA-chelated Fe(III) in BioDeNOx reactors

Reduction of EDTA-chelated Fe(III) is one of the core processes in the BioDeNOx process, a chemically enhanced technique for biological NOx removal from industrial flue gases. The capacity of Escherichia coli, three mixed cultures from full scale methanogenic granular sludge reactors, one denitrifying sludge, and a BioDeNOx sludge to reduce Fe(III)EDTA- (25 mM) was determined at 37 and 55 degrees C using batch experiments. Addition of catalytic amounts of sulfide greatly accelerated Fe(III)EDTA- reduction, indicating that biological Fe(III)EDTA- reduction is not a direct, enzymatic conversion but an indirect reduction with involvement of an electron-mediating compound, presumably polysulfides. It is suggested that not thermophilic dissimilatory iron-reducing bacteria but reducers of elemental sulfur or polysulfides are primarily involved in the reduction of EDTA-chelated Fe(III) in BioDeNOx reactors.     

Automatic detection of red lesions in digital color fundus photographs

The robust detection of red lesions in digital color fundus photographs is a critical step in the development of automated screening systems for diabetic retinopathy. In this paper, a novel red lesion detection method is presented based on a hybrid approach, combining prior works by Spencer et al. (1996) and Frame et al. (1998) with two important new contributions. The first contribution is a new red lesion candidate detection system based on pixel classification. Using this technique, vasculature and red lesions are separated from the background of the image. After removal of the connected vasculature the remaining objects are considered possible red lesions. Second, an extensive number of new features are added to those proposed by Spencer-Frame. The detected candidate objects are classified using all features and a k-nearest neighbor classifier. An extensive evaluation was performed on a test set composed of images representative of those normally found in a screening set. When determining whether an image contains red lesions the system achieves a sensitivity of 100% at a specificity of 87%. The method is compared with several different automatic systems and is shown to outperform them all. Performance is close to that of a human expert examining the images for the presence of red lesions.     

Toward automated segmentation of the pathological lung in CT

Conventional methods of lung segmentation rely on a large gray value contrast between lung fields and surrounding tissues. These methods fail on scans with lungs that contain dense pathologies, and such scans occur frequently in clinical practice. We propose a segmentation-by-registration scheme in which a scan with normal lungs is elastically registered to a scan containing pathology. When the resulting transformation is applied to a mask of the normal lungs, a segmentation is found for the pathological lungs. As a mask of the normal lungs, a probabilistic segmentation built up out of the segmentations of 15 registered normal scans is used. To refine the segmentation, voxel classification is applied to a certain volume around the borders of the transformed probabilistic mask. Performance of this scheme is compared to that of three other algorithms: a conventional, a user-interactive and a voxel classification method. The algorithms are tested on 10 three-dimensional thin-slice computed tomography volumes containing high-density pathology. The resulting segmentations are evaluated by comparing them to manual segmentations in terms of volumetric overlap and border positioning measures. The conventional and user-interactive methods that start off with thresholding techniques fail to segment the pathologies and are outperformed by both voxel classification and the refined segmentation-by-registration. The refined registration scheme enjoys the additional benefit that it does not require pathological (hand-segmented) training data.     

Physico-chemical factors affecting the E. coli removal in a rotating biological contactor (RBC) treating UASB effluent

The removal mechanism of E. coli from UASB effluent using a Rotating Biological Contractor (RBC) has been investigated. Preliminary batch experiments in a RBC indicate a first-order removal kinetics. Variation in the dissolved oxygen concentration and E. coli counts over the depth of the RBC has been recorded and indicates that the RBC is not a completely mixed reactor. Therefore batch experiments were carried out in a beaker where the different operating conditions can be controlled. Factors affecting the removal of E. coli via a biofilm system as stirring, dissolved oxygen concentration, pH, and addition of cationic polymer were investigated. The results obtained indicated that the most important removal mechanism of E. coli in the biofilm is the adsorption process, followed by sedimentation. Die-off is a relatively minor removal mechanism in an RBC system. Higher removal rate of E. coli was observed in an aerobic compared to an anaerobic biofilm system. Variation of dissolved oxygen concentration (3.3-8.7 mgl(-1)) and pH-values between 6.5 and 9.3 did not exert any significant effect on the removal rate of the E. coli by the heterotrophic biofilm. A rapid adsorption of E. coli to the biofilm occurred during the first days after adding the cationic polymer, after which the adsorption slowed down.