Deconvolution of Blood Microarray Data Identifies Cellular Activation Patterns in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a complex spectrum of cellular and molecular characteristics including several dramatic changes in the populations of peripheral leukocytes. These changes include general leukopenia, activation of B and T cells, and maturation of granulocytes. The manifestation of SLE in peripheral blood is central to the disease but is incompletely understood. A technique for rigorously characterizing changes in mixed populations of cells, microarray expression deconvolution, has been applied to several areas of biology but not to SLE or to blood. Here we demonstrate that microarray expression deconvolution accurately quantifies the constituents of real blood samples and mixtures of immune-derived cell lines. We characterize a broad spectrum of peripheral leukocyte cell types and states in SLE to uncover novel patterns including: specific activation of NK and T helper lymphocytes, relationships of these patterns to each other, and correlations to clinical variables and measures. The expansion and activation of monocytes, NK cells, and T helper cells in SLE at least partly underlie this disease's prominent interferon signature. These and other patterns of leukocyte dynamics uncovered here correlate with disease severity and treatment, suggest potential new treatments, and extend our understanding of lupus pathology as a complex autoimmune disease involving many arms of the immune system

Removing Water Droplets In Medical Images Using Textured Spectral Analysis

Some disease in human body is caused by accumulation of water molecules at particular place in an organ or entering of unwanted toxic foreign bodies. This may be in large or in negligible amounts. Many methods like CT, MRI can detect these abnormalities if present in appreciable amount. But if present in small amount, human vision on these scanned images cannot detect them. The visual appearance of moving water droplet is very complex. Each water droplet refracts and reflects both scene radiance and atmospheric illumination toward an observer. Water droplets are randomly distributed in space and move at high velocities. Thus, water droplets produce spatial and temporal intensity fluctuations in videos. Modelling, analysing and detecting these unwanted water molecules may benefit avoiding the negligence of presence of disease. In this paper, the proposed system that detect water molecules in the images of affected organ like lungs automatically .The crux idea is to exploit textural properties of droplets or fluid. To perpetrate this idea, we are aiming to model these droplets by laws of physical science and reveal this through block processing of image pixels. For partially occluded image portions, information of the image may be used to be applied in transform like DCT, blending functions and retrieve it. For fully occluded image, image completion techniques can be used. By using this we can detect the droplets even if they are in micron size

THE INFLUENCE OF EPITHELIAL SODIUM CHANNELS IN ISOLATED GOAT ILEUM SEGMENT; INTERACTION WITH STEROIDS

ABSTRACT: The contractile effect of Acetylcholine (Ach) in the isolated longitudinal ileal muscle of adult goats was studied over a varying concentration range. Ach produced a concentration dependent-response curve indicative of an interaction with muscarinic receptors in the ileum, with a maximum contraction seen at 12 µM. On the other hand, pretreatment with the ENaC blocker, Amiloride (100 µM) substantially reduced the Ach induced contractions by 67.11 %. However, pretreatment with Prednisolone (2mM) restored this effect and the relaxation induced was only 14.26 %. This change was found to be statistically significant. This study emphasizes the importance of ENaC channels in the goat intestinal smooth muscle

Use of amino acids as counterions improves the solubility of the BCS II model drug, Indomethacin

The number of new chemical entities (NCE) is increasing every day after the introduction of combinatorial chemistry and high throughput screening to the drug discovery cycle. One third of these new compounds have aqueous solubility less than 20µg/mL [1]. Therefore, a great deal of interest has been forwarded to the salt formation technique to overcome solubility limitations. This study aims to improve the drug solubility of a Biopharmaceutical Classification System class II (BCS II) model drug (Indomethacin; IND) using basic amino acids (L-arginine, L-lysine and L-histidine) as counterions. Three new salts were prepared using freeze drying method and characterised by FT-IR spectroscopy, proton nuclear magnetic resonance ((1)HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). The effect of pH on IND solubility was also investigated using pH-solubility profile. Both arginine and lysine formed novel salts with IND, while histidine failed to dissociate the free acid and in turn no salt was formed. Arginine and lysine increased IND solubility by 10,000 and 2296 fold, respectively. An increase in dissolution rate was also observed for the novel salts. Since these new salts have improved IND solubility to that similar to BCS class I drugs, IND salts could be considered for possible waivers of bioequivalence

TGFβ2 and TGFβ3 isoforms drive fibrotic disease pathogenesis.

Transforming growth factor-β (TGFβ) is a key driver of fibrogenesis. Three TGFβ isoforms (TGFβ1, TGFβ2, and TGFβ3) in mammals have distinct functions in embryonic development; however, the postnatal pathological roles and activation mechanisms of TGFβ2 and TGFβ3 have not been well characterized. Here, we show that the latent forms of TGFβ2 and TGFβ3 can be activated by integrin-independent mechanisms and have lower activation thresholds compared to TGFβ1. Unlike TGFB1, TGFB2 and TGFB3 expression is increased in human lung and liver fibrotic tissues compared to healthy control tissues. Thus, TGFβ2 and TGFβ3 may play a pathological role in fibrosis. Inducible conditional knockout mice and anti-TGFβ isoform-selective antibodies demonstrated that TGFβ2 and TGFβ3 are independently involved in mouse fibrosis models in vivo, and selective TGFβ2 and TGFβ3 inhibition does not lead to the increased inflammation observed with pan-TGFβ isoform inhibition. A cocrystal structure of a TGFβ2-anti-TGFβ2/3 antibody complex reveals an allosteric isoform-selective inhibitory mechanism. Therefore, inhibiting TGFβ2 and/or TGFβ3 while sparing TGFβ1 may alleviate fibrosis without toxicity concerns associated with pan-TGFβ blockade