Accommodative esotropia: An outcome analysis from a tertiary center in Oman.

AIM: The aim of this study is to determine the outcome of accommodative esotropia (ET) and influencing factors in young Omani children. SUBJECTS AND METHODS: In this retrospective cohort, children diagnosed with accommodative ET who had followed up in a tertiary hospital from 2006 to 2011 were identified. Parameters studied included cycloplegic refraction and its change with time, ocular alignment, binocularity, visual acuity (VA), amblyopia, and requirement for surgery. RESULTS: A total of 51 patients were identified. Twenty-four patients were diagnosed with fully accommodative ET (FAET) and 27 with partially accommodative ET (PAET). The mean (± standard deviation [SD]) age of onset and reporting were 2.6 (±1.58) and 3.2 (±1.84) years in the two groups, respectively. The mean (SD) cycloplegic refraction at presentation was 4.50 (±1.66) in the FAET group and 3.65 (±1.67) in the PAET group. Anisometropia was present in 28% of patients. The mean follow-up period was 4.9 years. The following were detected in the final visit. A reduction in amblyopia from 43% to 6% of patients, binocularity in 75% of patients, and a mean increase of 0.64 (±1.3) D in cycloplegic refraction from the first visit (P = 0.005). The mean angle of deviation at near and distance was 29.86 (±15.21) and 17.80 (±10.14) prism diopters, respectively, in FAET patients and 30.15 (±14.83) and 29.53 (±15.53), respectively, in PAET patients. Thirty-seven percent of the PAET patients underwent surgery within 5 years from diagnosis. All participants in this cohort continued to wear glasses in the last follow-up visit. CONCLUSION: Most children with refractive accommodative ET have an excellent outcome in terms of VA and binocular vision. The PAET group was characterized by delayed reporting, the presence of anisometropia, and lower hypermetropia. Further study is required to determine the possibility of weaning glasses in FAET patients.

Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows selective expression in excitatory neurons with high expression in the synapses.

SLC38A6 is one of the newly found members of the solute carrier 38 family consisting of total 11 members, of which only 6 have been characterized so far. Being the only glutamine transporter family expressed in the brain, this family of proteins are most probably involved in the regulation of the glutamate-glutamine cycle, responsible for preventing excitotoxicity. We used immunohistochemistry to show that SLC38A6 is primarily expressed in excitatory neurons and is not expressed in the astrocytes. Using proximity ligation assay, we have quantified the interactions of this SLC38 family protein with other proteins with known localization in the cells, showing that this transporter is expressed at the synapses. Moreover, this study has enabled us to come up with a model suggesting sub-cellular localization of SLC38A6 at the synaptic membrane of the excitatory neurons.

Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells.

BACKGROUND: Chemoresistance is a major factor involved in a poor response and reduced overall survival in patients with advanced breast cancer. Although extensive studies have been carried out to understand the mechanisms of chemoresistance, many questions remain unanswered. METHODS: In this research, we used two isogenic MCF-7 breast cancer cell lines selected for resistance to doxorubicin (MCF-7DOX) or docetaxel (MCF-7TXT) and the wild type parental cell line (MCF-7CC) to study mechanisms underlying acquired resistance to taxanes in MCF-7TXT cells. Cytotoxicity assay, immunoblotting, indirect immunofluorescence and live imaging were used to study the drug resistance, the expression levels of drug transporters and various tubulin isoforms, apoptosis, microtubule formation, and microtubule dynamics. RESULTS: MCF-7TXT cells were cross resistant to paclitaxel, but not to doxorubicin. MCF-7DOX cells were not cross-resistant to taxanes. We also showed that multiple mechanisms are involved in the resistance to taxanes in MCF-7TXT cells. Firstly, MCF-7TXT cells express higher level of ABCB1. Secondly, the microtubule dynamics of MCF-7TXT cells are weak and insensitive to the docetaxel treatment, which may partially explain why docetaxel is less effective in inducing M-phase arrest and apoptosis in MCF-7TXT cells in comparison with MCF-7CC cells. Moreover, MCF-7TXT cells express relatively higher levels of ß2- and ß4-tubulin and relatively lower levels of ß3-tubulin than both MCF-7CC and MCF-7DOX cells. The subcellular localization of various ß-tubulin isoforms in MCF-7TXT cells is also different from that in MCF-7CC and MCF-7DOX cells. CONCLUSION: Multiple mechanisms are involved in the resistance to taxanes in MCF-7TXT cells. The high expression level of ABCB1, the specific composition and localization of ß-tubulin isoforms, the weak microtubule dynamics and its insensitivity to docetaxel may all contribute to the acquired resistance of MCF-7TXT cells to taxanes.