Variations in 123I-metaiodobenzylguanidine (MIBG) late heart mediastinal ratios in chronic heart failure: a need for standardisation and validation

BACKGROUND: There is lack of validation and standardisation of acquisition parameters for myocardial (123)I-metaiodobenzylguanidine (MIBG). This lack of standardisation hampers large scale implementation of (123)I-MIBG parameters in the evaluation of patients with chronic heart failure (CHF). METHODS: In a retrospective multi-centre study (123)I-MIBG planar scintigrams obtained on 290 CHF patients (82% male; 58% dilated cardiomyopathy; New York Heart Association [NYHA classification] > I) were reanalysed to determine the late heart-to-mediastinum ratio (H/M). RESULTS: There was a large variation in acquisition parameters. Multivariate forward stepwise regression showed that a significant proportion (31%, p < 0.001) of the variation in late H/M could be explained by a model containing patient-related variables and acquisition parameters. Left ventricular ejection fraction (p < 0.001), type of collimation (p < 0.001), acquisition duration (p = 0.001), NYHA class (p = 0.028) and age (p = 0.034) were independent predictors of late H/M. CONCLUSIONS: Acquisitions parameters are independent contributors to the variation of semi-quantitative measurements of cardiac (123)I-MIBG uptake. Improved standardisation of cardiac (123)I-MIBG imaging parameters would contribute to increased clinical applicability for this procedur

Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic nonsteroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may be caused by fungal or bacterial microorganisms. Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases. The key intermediate of the paracetamol degradation pathways is hydroquinone. Sometimes, after hydrolysis of this drug, 4- aminophenol is formed, which is a dead-end metabolite. Ibuprofen is metabolized by hydroxylation or activation with CoA, resulting in the formation of isobutylocatechol. The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of over-the-counter antiinflammatory drugs, their sources and the biotransformation and/or biodegradation pathways of these drugs

Earthquake nucleation in weak subducted carbonates

Ocean-floor carbonate- and clay-rich sediments form major inputs to subduction zones, especially at low-latitude convergent plate margins. Therefore, knowledge of their frictional behaviour is fundamental for understanding plate-boundary earthquakes. Here we report results of mechanical tests performed on simulated fault gouges prepared from ocean-floor carbonates and clays, cored during IODP drilling offshore Costa Rica. Clay-rich gouges show internal friction coefficients (that is, the slope of linearized shear stress versus normal stress data) of μint = 0.44 − 0.56, irrespective of temperature and pore-fluid pressure (Pf). By contrast, μint for the carbonate gouge strongly depends on temperature and pore-fluid pressure, with μint decreasing dramatically from 0.84 at room temperature and Pf = 20 MPa to 0.27 at T = 140 °C and Pf = 120 MPa. This effect provides a fundamental mechanism of shear localization and earthquake generation in subduction zones, and makes carbonates likely nucleation sites for plate-boundary earthquakes. Our results imply that rupture nucleation is prompted by a combination of temperature-controlled frictional instability and temperature- and pore-pressure-dependent weakening of calcareous fault gouges

Overproduction of salicylic acid in plants by bacterial transgenes enhances pathogen resistance

After a hypersensitive response to invading pathogens, plants show elevated accumulation of salicylic acid (SA), induced expression of plant defense genes, and systemic acquired resistance (SAR) to further infection by a broad range of pathogens. There is compelling evidence that SA plays a crucial role in triggering SAR. We have transformed tobacco with two bacterial genes coding for enzymes that convert chorismate into SA by a two-step process. When the two enzymes were targeted to the chloroplasts, the transgenic (CSA, constitutive SA biosynthesis) plants showed a 500- to 1,000-fold increased accumulation of SA and SA glucoside compared to control plants. Defense genes, particularly those encoding acidic pathogenesis-related (PR) proteins, were constitutively expressed in CSA plants. This expression did not affect the plant phenotype, but the CSA plants showed a resistance to viral and fungal infection resembling SAR in nontransgenic plants.Ministry of Economic Affairs, the Ministry of Education, Culture and Science, and the Ministry of Agriculture, Nature Management and Fishery in the framework of a research program of the Association of Biotechnology Centres in the Netherlands (ABON)Peer reviewe