Design and Development of a Medical Image Databank for Assisting Studies in Radiomics

Journal of Digital Imaging - CompreHensive Digital ArchiVe of Cancer Imaging - Radiation Oncology (CHAVI-RO) is a multi-tier WEB-based medical image databank. It supports archiving de-identified...     

Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase

Background and purpose:

Nitric oxide (NO) promotes angiogenesis by activating endothelial cells. Thalidomide arrests angiogenesis by interacting with the NO pathway, but its putative targets are not known. Here, we have attempted to identify these targets.

Experimental approach:

Cell-based angiogenesis assays (wound healing of monolayers and tube formation in ECV304, EAhy926 and bovine arterial endothelial cells), along with ex vivo and in vivo angiogenesis assays, were used to explore interactions between thalidomide and NO. We also carried out in silico homology modelling and docking studies to elucidate possible molecular interactions of thalidomide and soluble guanylyl cyclase (sGC).

Key results:

Thalidomide inhibited pro-angiogenic functions in endothelial cell cultures, whereas 8-bromo-cGMP, sildenafil (a phosphodiesterase inhibitor) or a NO donor [sodium nitroprusside (SNP)] increased these functions. The inhibitory effects of thalidomide were reversed by adding 8-bromo-cGMP or sildenafil, but not by SNP. Immunoassays showed a concentration-dependent decrease of cGMP in endothelial cells with thalidomide, without affecting the expression level of sGC protein. These results suggested that thalidomide inhibited the activity of sGC. Molecular modelling and docking experiments revealed that thalidomide could interact with the catalytic domain of sGC, which would explain the inhibitory effects of thalidomide on NO-dependent angiogenesis.

Conclusion and implications:

Our results showed that thalidomide interacted with sGC, suppressing cGMP levels in endothelial cells, thus exerting its anti-angiogenic effects. These results could lead to the formulation of thalidomide-based drugs to curb angiogenesis by targeting sGC.     

Research Goal-Driven Data Model and Harmonization for De-Identifying Patient Data in Radiomics

Journal of Digital Imaging - There are various efforts in de-identifying patient’s radiation oncology data for their uses in the advancement of research in medicine. Though the task of...     

Acephate immunotoxicity in White Leghorn cockerel chicks upon experimental exposure

Immunotoxicity for subacute exposure to acephate (O,S-dimethyl-acetylphosphoramidothioate) was assessed in day old White Leghorn (WLH) cockerel chicks. The chicks were divided into five groups. Groups C1 and C2 served as plain control and vehicle control respectively. Chicks of groups T1, T2 and T3 were administered acephate suspended in groundnut oil at 21.3mg/kg, 28.4mg/kg and 42.6mg/kg respectively orally for 28 days. A non-significant reduction in total leukocyte count was observed. Although, anti-Newcastle Disease Virus (NDV) antibody titer, serum total protein (TP), serum globulin, serum albumin and organ:body weight ratios of immune organs were significantly suppressed. The delayed type hypersensitivity response to 2,4-dinitro-1-chlorobenzene (DNCB) was not significantly altered. Histopathologically, bursa and spleen showed mild depletion of lymphocytes. Furthermore, DNA fragmentation assay was performed and detected ladder pattern (180bp) in DNA. It was concluded that subacute acephate exposure at low concentrations may affect immune responses in avian species.     

Hematological and Immunological Changes Due to Short-term Oral Administration of Acephate

To evaluate immunotoxicological effects of environmental chemical, subacute toxicity of repeated (28 day) oral administration of acephate (Ace) in BALB/c mice was assessed. Thirty two (sixteen male and sixteen female) mice were divided into four different groups with each group containing eight (four male and four female) mice. Mice of Group C1 were administered normal saline only and served as control. Group T1 was given 1/40(th) of apparent LD(50) (ALD(50)) (8.78 mg/kg), and group T2 was put on 1/30(th) of ALD(50) [11.7 mg/kg], while group T3 received 1/20(th) of ALD(50) [17.55 mg/kg] of Ace suspended in normal saline. The blood samples were collected from mice after 28 days of oral administration and analyzed for hematological, biochemical, and immunological parameters. The study showed that hematological parameters (monocytes and granulocytes) remained unaffected except total leukocyte count and lymphocyte which were decreased highly significantly [P≤0.01] in mice of group T3 on the 28(th) day of experiment. Serum total protein (TP) and serum globulin decreased significantly in mice of treatment groups dose dependently; however, no significant change was seen in serum albumin. Progressive increase in live body weight of mice decreased significantly in extremely toxic group only while spleen:body weight ratio decreased significantly in dose-dependent manner. Furthermore, Ace produced suppressed humoral immune response and the delayed-type hypersensitivity response to Sheep red blood cells (SRBCs) was altered nonsignificantly. The results of this study describe the suppression of immune responses following exposure to Ace at low concentrations in experimental mice.