Multi-Target Drugs: The Trend of Drug Research and Development

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target–target and drug–drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future

Vortex tracking on visualized temperature fields in a rotating Rayleigh-Benard convection

We established a vortex detection method using instantaneous temperature fields that were visualized using thermochromic liquid crystals (TLCs) to investigate behaviors of vortical structures in a rotating Rayleigh-Benard convection. Experimental testing was performed at a fixed Rayleigh number in water containing encapsulated TLCs. Vortices were recognized as undulations that appear in the horizontal temperature fields, thus making vortex detection with high spatial resolution possible, and this enabled quantitative investigation of the dynamics of vortical structures. Standard template matching was used to detect individual vortices on visualized temperature fields, and two-dimensional curved surface fitting was adopted to remove erroneous detections and to evaluate shapes of local temperature fields corresponding to vortical structures. Additionally, vortex tracking clearly showed geometric advection pattern of vortical structures

Expression of IL-2R, IL-4R, IL-6R on peripheral blood lymphocytes in systemic lupus erythematosus and correlation with disease activity: a prospective study.

AIMS: To study the expression of interleukin-2 receptor (IL-2R), interleukin-4 receptor (IL-4R) and interleukin-6 receptor (IL-6R) on peripheral blood lymphocytes (PBL) in patients with systemic lupus erythematosus (SLE); to correlate the level of expression of these receptors with SLE disease activity. METHODS: Peripheral blood lymphocytes were studied by a high sensitivity flow cytometry technique using monoclonal antibodies directed against CD25 (IL-2R alpha chain), CD122 (IL-2R beta chain), CD124 (IL-4R), and CD126 (IL-6R). SLE disease activity was scored using the SLE Disease Activity Index, C3 and C4 concentrations, anti-dsDNA level, and absolute lymphocyte count. RESULTS: Compared with normal controls, PBL from patients with SLE had a higher percentage of CD25+ cells (median 20.8% v 16.5%) and a lower percentage of CD122+ cells (median 13.1% v 22.4%). The difference in CD122+ cells was greater in the CD122weak population than the CD122strong (natural killer cell) population. The percentages of CD124+ and CD126+ PBLs in patients with SLE and controls were similar. On CD25+ cells, the relative antigenic level of the IL-2R alpha chain was significantly higher in patients with SLE (median 2.01 v 1.81). The relative antigenic levels of CD122+, CD124+ and CD126+ cells were similar in patients and controls. Neither the percentages nor the relative antigenic levels of all of these cytokine receptors were correlated with any of the parameters of disease activity. CONCLUSION: Lymphocyte activation in patients with SLE was evident from the increase in CD25 expression on PBL, with a reciprocal decrease in CD122 expression. As the expression of IL-2R, IL-4R, IL-6R did not correlate with disease activity, it seems that these cytokine/receptor systems do not play a direct role in disease activation in SLE

Levels of IL-12 in the sera of patients with systemic lupus erythematosus (SLE)—relation to Th1- and Th2-derived cytokines

IL-12 is a cytokine that induces Th1-derived cytokines (interferon-gamma (IFN-γ) and IL-2). The significance of IL-12 in human autoimmunity is no clear, and the serum levels of IL-12 in SLE are not clearly established. Therefore, we examined the levels of IL-12 in 39 patients with active SLE, with sandwich ELISA. The levels of IL-12 in patients were significantly higher than in normal subjects. Patients with high levels of IL-12 also had high levels of IFN-γ, while their levels of IL-13 were significantly lower than in patients with normal levels of IL-12. Patients with pulmonary involvement had high levels of IL-12, and steroid therapy decreased the IL-12 level in three patients. In a retrospective study of seven patients, various changes of IL-12 and IL-13 were recognized before disease flare. Thus, in SLE patients, the level of IL-12 was increased and this increase was related to the change of Th1- or Th2-derived cytokines with some organ involvement

Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus

To investigate the production mechanism and proinflammatory role of the cytokine interleukin (IL-18) in lupus nephritis, we investigated the plasma concentrations of IL-18 and nitric oxide (NO) and the release of IL-18 and NO from mitogen-activated peripheral blood monomuclear cells (PBMC), in 35 SLE patients with renal disease (RSLE), 37 patients without renal disease (SLE) and 28 sex- and age-matched healthy control subjects (NC). IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Gene expressions of IL-18 and IL-18 receptor were analysed by RT-PCR. Plasma IL-18 and NO concentrations were significantly higher in RSLE than NC (both P < 0·01). Elevation of plasma IL-18 in RSLE correlated positively and significantly with SLE disease activity index and plasma NO concentration (r = 0·623, P < 0·0001 and r = 0·455, P = 0·017, respectively), and the latter also showed a positive and significant correlation with plasma creatinine (r = 0·410, P = 0·034) and urea (r = 0·685, P < 0·0001). There was no significant difference in gene expressions of IL-18 and IL-18 receptor in PBMC among RSLE, SLE and NC. Percentage increase in culture supernatant IL-18 concentration was significantly higher in RSLE than SLE and NC (both P < 0·05). The basal NO release was significantly higher in RSLE than that in SLE and NC (both P < 0·005). IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE