Comparison of the efficacy and invasiveness of manual and automated gonioscopy.

PURPOSE: To compare the efficacy and invasiveness of manual gonioscopy and automated 360-degree gonioscopy. METHOD: Manual and automated gonioscopy were performed on 70 patients with glaucoma. Manual gonioscopy was performed by a glaucoma specialist and an ophthalmology resident, and automated gonioscopy (GS-1) was performed by orthoptists. We compared the examination time for acquiring gonioscopic images (GS-1: 16 directions; manual gonioscopy: 8 directions). Furthermore, we compared the pain and discomfort scores during the examination using the Individualized Numeric Rating Scale. Among the images acquired by automated gonioscopy, we also evaluated the percentages of acquired images that could be used to determine the angle opening condition. RESULTS: The examination time was not significantly different between manual (80.2±28.7) and automated gonioscopy (94.7±82.8) (p = 0.105). The pain score of automated gonioscopy (0.22±0.59) was significantly lower than that of manual gonioscopy (0.55±1.11) (p = 0.025). The discomfort score was not significantly different between manual (1.34±1.90) and automated gonioscopy (1.06±1.50) (p = 0.165). Automated gonioscopy successfully acquired clear gonioscopic images in 93.4% of the total images. CONCLUSION: Automated gonioscopy is comparable in examination time and invasiveness to manual gonioscopy and may be useful for 360-degree iridocorneal angle evaluation.

Trametinib suppresses chemotherapy-induced cold and mechanical allodynia via inhibition of extracellular-regulated protein kinase 1/2 activation.

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of some anti-cancer drugs and leads to discontinuation of chemotherapy and detrimental dose reductions, thereby affecting the quality of life of cancer patients. Currently, no treatment can effectively prevent or treat chemotherapy-induced neuropathy. Therefore, understanding its underlying molecular mechanisms may help to identify novel therapies for treating it. Some disease-induced neuropathy involve the activation of mitogen-activated protein kinases (MAPKs), such as extracellular-regulated protein kinase 1/2 (ERK1/2). In the present study, we investigated whether ERK1/2 inhibition can prevent chemotherapy-induced neuropathy. We found that trametinib, an MEK inhibitor, suppressed oxaliplatin-, paclitaxel-, vincristine-, and bortezomib-induced cold and mechanical allodynia in mice. In addition, treatment with oxaliplatin, paclitaxel, vincristine, or bortezomib enhanced ERK1/2 and c-Jun N-terminal kinase (JNK) phosphorylation in the spinal cord lumbar segments 4-6, and when combined with trametinib, can prevent chemotherapy-induced neuropathy via the suppression of ERK1/2 activation, but does not affect JNK activation. In conclusion, we demonstrated that the disruption of this pathway by MEK inhibitors suppresses oxaliplatin-, paclitaxel-, vincristine-, and bortezomib-induced neuropathy. This suggests that inhibition of the MEK/ERK pathway could prevent chemotherapy-induced neuropathy and MEK inhibitors could be used in combination with anti-tumor drugs during pharmacotherapy.

Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins.

Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5-FU)-induced cell death in NHOK cells. In addition, rebamipide increased the levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions, and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the enhanced expression of Bax and Bim. These findings suggest that rebamipide can potentially be used for the protection of oral mucosa from chemotherapy-induced mucositis. This is the first study that elucidates the specific molecular pathway for the cytoprotective effect of rebamipide.