Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling

Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).     

Entrapment of Humic Acid in a Sol-Gel Matrix—A New Tool for Sorption Studies

Humic substances are natural complexed mixtures of organic compounds originated from the decomposition of plant and animal residues. These compounds are ubiquitous in soils, sediments, surface waters and groundwaters. They contain both hydrophobic and hydrophilic moieties, able to interact with hydrophobic organic contaminants and with heavy metals. These sorption interactions play a crucial role in contaminants fate and transport and their understanding and quantification are essential for modeling and predictions. However, sorption analyses frequently suffer from experimental problems. A novel idea presented in this study is to use sol-gel as an inert matrix to immobilize (entrap) specific, well defined, humic molecules which then be used in sorption studies. We developed a successful procedure for the immobilization of humic acid (HA) in a sol-gel matrix. After gelation and drying, the doped gel was crushed and washed several times, yielding a very stable product. It was then used in a series of batch experiments, studying the sorption of several polycyclic aromatic hydrocarbons (PAHs) with Aldrich HA. The sorption coefficients (K _oc) obtained with the immobilized HA were highly correlated with the values expected based on the hydrophobicity of the contaminants. We concluded that the entrapped HA retained its original properties and that it was accessible to the external contaminants through the pore network.     

Evaluating microbial activity in composts using microcalorimetry

Microcalorimetric isothermal monitoring was carried out for compost and compost-containing growing medium, to provide fingerprints of compost microbial activity at different conditions. Microbial activity is a key property of composts used in agricultural practice. Two aspects are addressed in this study: (1) microcalorimetric evaluation of compost response to glucose as a model stimulating agent; (2) examination of the impact of compost pre-drying and re-wetting on its biological activity.

Addition of glucose solution to the compost involved a strong increase in microbial activity, which was associated with a significant heat evolution without a lag period. In certain cases, this heat evolution was of complicated shape thus manifesting the heterogeneity of microbial populations in composts. Relation between cumulative energy evolved and the amount of added glucose was found to be helpful in distinguishing between aerobic and anaerobic regime of compost microbial activity. As distinct from non-dried compost or growing mixture, glucose addition to samples pre-dried at 65 °C resulted in delayed heat response with initial exponential-like heat evolution. This delay in heat evolution suggests that biological activity was significantly suppressed upon compost drying. Such a temperature-induced inactivation process might also result in dominance of a relatively homogeneous microbial population which survived the heating, thus involving a smooth, exponential-like initial step of the heat evolution. Noteworthy, addition of water (without glucose) to pre-dried compost results in an outburst of activity as compared with non-dried compost. This heat evolution outburst was also characterized by a lag period and an initial exponential-like phase. The heat evolution obtained with pre-dried compost upon water addition was not related to the compost wetting energy but rather reflected the formation of new carbon source due to the changes in compost organic matter upon heating or to the dead biomass of those microbial populations that did not resist the compost heating/drying.     

The Metabolostasis Network and the Cellular Depository of Aggregation-Prone Metabolites

The vital role of metabolites across all branches of life and their involvement in various disorders have been investigated for decades. Many metabolites are poorly soluble in water or in physiological buffers and tend to form supramolecular aggregates. On the other hand, in the cell, they should be preserved in a pool and be readily available for the execution of biochemical functions. We thus propose that a quality-control network, termed “metabolostasis”, has evolved to regulate the storage and retrieval of aggregation-prone metabolites. Such a system should control metabolite concentration, subcellular localization, supramolecular arrangement, and interaction in dynamic environments, thus enabling normal cellular physiology, healthy development, and preventing disease onset. The paradigm-shifting concept of metabolostasis calls for a reevaluation of the traditional view of metabolite storage and dynamics in physiology and pathology and proposes unprecedented directions for therapeutic targets under conditions where metabolostasis is imbalanced.