Orally Administrated Glutamate Restored EAAT1 and 3 Expression Levels Suppressed in 5-Fluorouracil-damaged Intestinal Epithelial Cells.

BACKGROUND/AIM: 5-Fluorouracil (5-FU) treatment induces intestinal mucositis, with diarrhea as the primary symptom. Mucositis significantly reduces patients' quality of life (QOL). Amino acids such as glutamate are beneficial for treating gastrointestinal disorders; however, the underlying mechanism remains unclear. Therefore, this study aimed to clarify the role of excitatory amino acid transporters (EAATs) in 5-FU-induced intestinal injury. MATERIALS AND METHODS: The rat intestinal epithelial cell line (IEC-6) was used to evaluate whether the EAAT inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) affects 5-FU-induced cytotoxicity. Mice with 5-FU-induced mucositis were used to determine the effects of glutamate on EAATs expression levels. RESULTS: Treatment with L-trans-PDC suppressed IEC-6 cell growth. It also exacerbated the 5-FU-induced cell growth suppression and increased inflammatory cytokine expression. In addition, mice treated with 5-FU+Glutamate showed higher EAAT1,3 expression than 5-FU only-treated mice. CONCLUSION: Decreased EAAT levels worsen intestinal cell damage caused by 5-FU, suppress cell growth, and induce inflammation. This study contributes to the understanding EAAT and its relationship with intestinal mucositis, which can aid in the development of novel preventive strategies for cancer chemotherapy.

Human iris pigment epithelial cells suppress T-cell activation via direct cell contact.

The purposes of the present study were to investigate whether cultured human iris pigment epithelial (hIPE) cells acquire the ability to modify T-cell activation, and if so, to identify the mechanism. Human IPE cells were prepared from patients who underwent glaucoma surgery, and were cultured in RPMI 1640 medium containing 10% fetal calf serum for 4-7 days. Expression of MHC molecules and co-stimulatory molecules on cultured hIPE cells either unstimulated or stimulated with IFN-gamma was examined by FACS. In addition, peripheral blood T cells were incubated with cultured hIPE cells prepared from the same patients and anti-CD3 antibody in a transwell culture system, or in the presence of anti-PD-L1 and PD-L2 antibodies, and T cell proliferation was assessed by [3H]-thymidine incorporation. The hIPE cells inhibited anti-CD3-driven T-cell activation but the inhibition was diminished when tested in the transwell culture system, indicating that a contact-dependent mechanism is important in the immunoregulatory roles of hIPE. Although cultured hIPE cells expressed Class I and PD-L1 but not Class II or PD-L2, all these molecules were observed on hIPE cells cultured in the presence of IFN-gamma. Blocking antibodies against both PD-L1 and PD-L2 reduced the immunoregulatory activity of hIPE cells. Our data indicates that cultured hIPE cells inhibit T-cell activation by T-cell receptor ligation, which is mediated by cell-to-cell contact in part via the PD-L1 and PD-L2 pathways.

Comparison of the additive effects of nipradilol and carteolol to latanoprost in open-angle glaucoma.

PURPOSE: To compare the effects of nipradilol and carteolol on intraocular pressure (IOP) when added to latanoprost treatment for glaucoma patients. METHODS: Fifty patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two groups randomly. One group received nipradilol 0.25% twice daily (nipradilol preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily (carteolol preceding group; n = 25), for 3 months in addition to latanoprost. Then, nipradilol and carteolol were switched, and the subjects were treated for 3 more months. One eye was selected randomly for analysis. RESULTS: In the nipradilol preceding group, IOP was 21.4 +/- 2.3 mmHg (mean +/- SD) at baseline, and 16.8 +/- 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of nipradilol decreased IOP to 15.8 +/- 1.7 mmHg, and the change to carteolol, to 15.3 +/- 2.0 mmHg. In the carteolol preceding group, IOP was 21.2 +/- 2.0 mmHg at baseline, and 17.0 +/- 2.1 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 +/- 1.8 mmHg, and the change to nipradilol, to 16.3 +/- 1.9 mmHg. Additional IOP reduction was greater with carteolol than with nipradilol (cross-over analysis of variance; P = 0.0005). CONCLUSIONS: Both nipradilol and carteolol have additive effects when used in combination with latanoprost. Carteolol, however, may have a more potent effect than nipradilol.

Resuturing the scleral flap through conjunctiva for treatment of excess filtration.

PURPOSE: To elevate the intraocular pressure (IOP) in eyes with persistent hypotony caused by excess filtration after trabeculectomy. DESIGN: Interventional case series. METHODS: The scleral flap was sutured directly through the conjunctival flap using a round, tapered needle with a 10-0 nylon suture. This procedure has been performed in 10 eyes. RESULTS: The IOP elevated from 2.6 (+/- 1.0) mm Hg to 8.8 (+/- 3.7) mm Hg in 1 week and has been maintained between 6 to 14 mm Hg during the follow-up. Hypotony maculopathy has disappeared in nine eyes. The suture was buried in the conjunctiva spontaneously in 1 week in all cases. No complications developed. CONCLUSIONS: Suturing the scleral flap directly through the conjunctival flap is a simple and effective modality to treat the hypotony caused by excess filtration after trabeculectomy.

Study of retinal nerve fiber layer thickness within normal hemivisual field in primary open-angle glaucoma and normal-tension glaucoma.

PURPOSE: To determine if nerve fiber layer thickness (NFLT) in glaucoma patients decreases before the development of visual field loss, and if there is a difference in the thinning of NFLT between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) eyes. METHODS: Thirty patients (33 eyes) with POAG and 31 patients (31eyes) with NTG, who had visual field defects localized in either the upper or the lower hemifield verified by Humphrey Field Analyzer (HFA), were measured for NFLT by scanning laser polarimetry (Nerve Fiber Analyzer). Twenty-three normal subjects (23 eyes) matched in refraction and age with the glaucoma patients were recruited as the control group. The total deviation (TD) in each hemifield obtained by HFA and the 180 degrees NFLT of each corresponding hemifield was calculated. Relationships between the TD of the normal or abnormal visual hemifield and the NFLT of the corresponding hemifield were compared among the POAG, NTG, and control groups. RESULTS: The NFLT of the corresponding normal hemifield was decreased both in the POAG group and in the NTG group when compared with the corresponding measurements in control subjects. In POAG eyes, thinning of the NFLT in the corresponding normal hemifield was more remarkable if the TD of the abnormal hemifield was greater, but this tendency was not observed in NTG eyes. CONCLUSION: NFLT is already decreased when the visual field is still normal both in POAG eyes and in NTG eyes. However, the pattern of retinal nerve fiber layer damage in POAG may differ from that in NTG.