The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its over expression in several types of cancers coupled with its ability to promote tumor growth and metastasis. In order to identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines which demonstrated potent inhibition of AXL in vitro (IC50 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

Background:

Transfusion-transmissible malaria (TTM) is a major concern in malaria endemic countries. A study was therefore conducted to know sero-prevalence of malaria in blood donors and the risk of TTM to multi-transfused patients at our hospital.

Materials and Methods:

Study subjects were: eligible blood donors (n = 1000), donors deferred due to history of fever in the last 3 months (n = 100), and multi-transfused patients (n = 200). Screening for malaria was done by slide microscopy, immunochromatographic rapid diagnostic test (RDT) for malaria antigen, and anti-malaria antibody by enzyme linked immunosorbent assay.

Results:

Malaria antibody prevalence in eligible donors and donors with history of fever, thalassemia patients, and in other multi-transfused patients was 16.9%, 22%, 6%, and 15%, respectively. None of the donors were positive for malaria on microscopic examination. None of the blood donors except one donor with history of fever, tested positive with RDT.

Conclusion:

Malaria antibody prevalence in blood donors at our center is high. As blood units donated by such donors have high-risk potential, special processing may be undertaken to reduce the risk of TTM.

Very few studies in humans have investigated the laboratory evidences suggestive of transfusion-associated immunologic changes. In this prospective study, we examined the effects of perioperative blood transfusion on immune response, by measuring various cytokines production, namely, interferon-gamma (IFN-γ), interleukin-10 (IL-10), and Fas Ligand (FasL). A total of 40 patients undergoing neurosurgery were randomly allocated into four groups: (a) no transfusion, (b) allogeneic non-leukofiltered transfusion, (c) prestorage leukofiltered transfusion, (d) autologous transfusion. Samples were collected before operation (day 0) and postoperative days (post-op) 1, 7, and 14. IFN-γ and IL-10 production capacity was measured in supernatant after whole blood culture and serum FasL levels in patients’ sera using commercially available ELISA kits. Change in ratios (cytokine value after PHA stimulation/control value) of IFN-γ and IL-10 and percentage change from baseline for serum FasL levels across different transfusion groups during the sampling period were calculated. There was an increase in IL-10 production in patients receiving allogeneic non-leukofiltered transfusion on days 1 and 7 (mean ratio 2.22 (± 2.16), 4.12 (± 1.71), 4.46 (± 1.97) on days 0, 1, and 7, respectively). Similarly there was a significant (P<0.05) decrease in IFN-γ production in patients who received allogeneic non-leukofiltered red cell transfusion on post-op days 1, 7, and 14 (mean ratio 6.88 (± 4.56), 2.53 (± 0.95), 3.04 (± 1.38) and 2.58 (± 1.48) on day 0, 1, 7, and 14, respectively). Serum FasL production was increased across all patients till 7th day except for ‘no transfusion’ group and this increase was most significant in the non-leukofiltered group. We conclude that one time transfusion leads to quantitative changes in levels of these cytokines largely through interplay of Th2/Th1 pathways in allogeneic nonleukofiltered blood transfusion; however, soluble mediators like FasL which are also present in autologous and leukofiltered blood products may contribute toward minor immunologic effect in these settings.

Background:

Despite the wide range of methods available for measurement of hemoglobin, no single technique has emerged as the most appropriate and ideal for a blood donation setup.

Materials and Methods:

A prospective study utilizing 1014 blood samples was carried out in a blood donation setting for quality evaluation of four methods of hemoglobin estimation along with cost analysis: Hematology cell analyzer (reference), HCS, CuSO4 method and HemoCue.

Results:

Mean value of HemoCue (mean ± SD = 14.7 ± 1.49 g/dl) was higher by 0.24 compared to reference (mean ± SD = 13.8 ± 1.52 g/dl) but not statistically significant ( P > 0.05). HemoCue proved to be the best technique (sensitivity 99.4% and specificity 84.4%) whereas HCS was most subjective with 25.2% incorrect estimations. CuSO4 proved to be good with 7.9% false results. Comparative cost analysis of each method was calculated to be 35 INR/test for HemoCue, 0.76 INR /test for HCS and 0.06-0.08 INR /test for CuSO4.

Conclusion:

CuSO4 method gives accurate results, if strict quality control is applied. HemoCue is too expensive to be used as a primary screening method in an economically restricted country like India.