The therapeutic use of Abs in cancer, autoimmunity, transplantation, and other fields is among the major biopharmaceutical advances of the 20th century. Broader use of Ab-based drugs is constrained because of their high production costs and frequent side effects. One promising approach to overcome these limitations is the use of highly diluted Abs, which are produced by gradual reduction of an Ab concentration to an extremely low level. This technology was used to create a group of drugs for the treatment of various diseases, depending on the specificity of the used Abs. Highly diluted Abs to IFN-g (hd-anti-IFN-g) have been demonstrated to be efficacious against influenza and other respiratory infections in a variety of preclinical and clinical studies. In the current study, we provide evidence for a possible mechanism of action of hd-anti-IFN-g. Using high-resolution solution nuclear magnetic resonance spectroscopy, we show that the drug induced conformational changes in the IFN-g molecule. Chemical shift changes occurred in the amino acids located primarily at the dimer interface and at the C-terminal region of IFN-g. These molecular changes could be crucial for the function of the protein, as evidenced by an observed hd-anti-IFN-g-induced increase in the specific binding of IFN-g to its receptor in U937 cells, enhanced induced production of IFN-g in human PBMC culture, and increased survival of influenza A-infected mice.

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In obese humans CT imaging is a validated method for follow up studies of adipose tissue distribution and quantification of visceral and subcutaneous fat. Equivalent methods in murine models of obesity are still lacking. Current small animal micro-CT involves long-term X-ray exposure precluding longitudinal studies. We have overcome this limitation by using a human medical CT which allows very fast 3D imaging (2 sec) and minimal radiation exposure. This work presents novel methods fitted to in vivo investigations of mice model of obesity, allowing (i) automated detection of adipose tissue in abdominal regions of interest, (ii) quantification of visceral and subcutaneous fat.For each mouse, 1000 slices (100µm thickness, 160 µm resolution) were acquired in 2 sec using a Toshiba medical CT (135 kV, 400mAs). A Gaussian mixture model of the Hounsfield curve of 2D slices was computed with the Expectation Maximization algorithm. Identification of each Gaussian part allowed the automatic classification of adipose tissue voxels. The abdominal region of interest (umbilical) was automatically detected as the slice showing the highest ratio of the Gaussian proportion between adipose and lean tissues. Segmentation of visceral and subcutaneous fat compartments was achieved with 2D ½ level set methods. Our results show that the application of human clinical CT to mice is a promising approach for the study of obesity, allowing valuable comparison between species using the same imaging materials and software analysis