Synthesis and biological evaluation of Schizandrin derivatives as tubulin polymerization inhibitors.

A series of oxime ester-derivatives were prepared by utilizing the schizandrin (1), a major compound isolated from Schisandra grandiflora, which is deployed in different traditional system of medicine. The in vitro antiproliferative activities of the synthesized compounds were assessed against a selected panel of human cancer cell lines (A549, RKO P3, DU145 and Hela) and normal cell (HEK293). Several of these derivatives were found more potent in comparison to parent compound, schizandrin (1). Particularly, 4a and 4b demonstrated potent activity against DU-145 and RKOP3 cell lines with IC50 values of 3.42 µM and 3.35 µM respectively. To characterize the molecular mechanisms involved in antitumoral activity, these two compounds, 4a and 4b were selected for further studies. Cell cycle analysis revealed that both the compounds were able to induce apoptosis and cell cycle arrest at G0/G1 phase. To know the extent of apoptosis in DU145 and RKOP3 cell lines, Annexin V-FITC were performed. Moreover, the tubulin polymerization assay indicated that 4a and 4b exhibits potent inhibitory effect on the tubulin assembly. Molecular docking studies and competitive binding assay also indicated that 4a and 4b effectively bind at the colchicine binding site of the tubulin.

Tay-Sach disease with "cherry-red spot"--first reported case in Malaysia.

We present a rare case of Tay-Sachs disease with retinal 'cherry-red spots' in a 19-month-old Malay child. Molecular genetic studies confirmed the diagnosis. The case highlights that 'cherry-red spot' is a useful clinical clue in Tay-Sachs disease and several other lysosomal storage disorders. It serves as an ideal illustration of the eye as a window to inborn error of metabolism.

Extraction and reconstruction of retinal vasculature.

Information about retinal vasculature morphology is used in grading the severity and progression of diabetic retinopathy. An image analysis system can help ophthalmologists make accurate and efficient diagnoses. This paper presents the development of an image processing algorithm for detecting and reconstructing retinal vasculature. The detection of the vascular structure is achieved by image enhancement using contrast limited adaptive histogram equalization followed by the extraction of the vessels using bottom-hat morphological transformation. For reconstruction of the complete retinal vasculature, a region growing technique based on first-order Gaussian derivative is developed. The technique incorporates both gradient magnitude change and average intensity as the homogeneity criteria that enable the process to adapt to intensity changes and intensity spread over the vasculature region. The reconstruction technique reduces the required number of seeds to near optimal for the region growing process. It also overcomes poor performance of current seed-based methods, especially with low and inconsistent contrast images as normally seen in vasculature regions of fundus images. Simulations of the algorithm on 20 test images from the DRIVE database show that it outperforms many other published methods and achieved an accuracy range (ability to detect both vessel and non-vessel pixels) of 0.91 - 0.95, a sensitivity range (ability to detect vessel pixels) of 0.91 - 0.95 and a specificity range (ability to detect non-vessel pixels) of 0.88 - 0.94.

Cost efficiency and cost effectiveness of cataract surgery at the Malaysian Ministry of Health ophthalmic services.

PURPOSE: To determine the cost efficiency and to compare the cost effectiveness of conventional extracapsular cataract surgery (ECCE) and phacoemulsification at three hospitals of the Malaysian Ministry of Health (MOH). METHODS: Patient demography, pre-operative visual acuity, intra-operative complications, post-operative complications and post-operative visual acuity were recorded for two hundred and forty seven of the 400 patients who underwent cataract surgery during a 2-week period. The cost of surgery, which included capital, staff and overhead, and patient care consumable costs were assessed prospectively in 8 randomly sampled patients over a 3-month period. Cost efficiency refers to cost per cataract surgery. Cost effectiveness refers to cost per successful cataract surgery. This is estimated by the ratio of cost efficiency to the proportion of successful cataract surgery. Successful surgery was defined as best-corrected visual acuity (BCVA) of better than 6/12 at 3 months post-operatively. RESULTS: Proportion of patients who had post-operative visual acuity of 6/12 or better was higher in phacoemulsification group (94%) than in the ECCE group (81%). Conventional extracapsular cataract surgery with intraocular lens implant costs RM3442 (USD 905.79) and phacoemulsification with intraocular lens implant costs RM4288 (USD 1128.42). DISCUSSION: There was no significant difference in cost effectiveness between ECCE and phacoemulsification. The cost of cataract surgery in the MOH hospital was found to be high due to the high overhead costs.