[Pilot study on clinical effects of rebamipide gargle against oral mucositis induced by fluoropyrimidines].

Rebamipide, a cytoprotective agent, has been suspected to attenuate oral mucositis through anti-inflammatory potentials and induction of endogenous prostaglandin synthesis. This prospective study was designed to assess the clinical efficacy of rebamipide gargle against oral mucositis, which is induced by fluoropyrimidines in patients with stomach and colorectal cancer. We first conducted a pilot study on gargle flavors, because the solution in this agent has a strong and bitter after taste. Nine kinds of flavors were prepared, and six characteristics were evaluated by ten volunteers: sourness, bitterness, sweetness, remain, after taste, and hard to drink. We determined the contents of rebamipide using HPLC, which showed stability in an acidic condition. Finally, we decided that 100% Pokka Lemon should be used as the flavor of the rebamipide solution. A clinical study was then started to compare the preventive effects rebamipide gargle and placebo have on stomatitis, quality of life (QOL), and the therapeutic effects of chemotherapy.

PACAP induces neurite outgrowth in cultured trigeminal ganglion cells and recovery of corneal sensitivity after flap surgery in rabbits.

PURPOSE: To evaluate the ability of pituitary adenylate cyclase-activating polypeptide (PACAP) to induce growth of neuronal processes in cultured trigeminal ganglion cells, and to accelerate neurite outgrowth and recovery of corneal sensitivity after creation of a corneal flap in a rabbit model of laser-assisted in situ keratomileusis (LASIK) surgery. DESIGN: Animal study. METHODS: The cDNA of rabbit PACAP was sequenced, and the expression of PACAP receptors in the trigeminal ganglia from rabbits was quantified by quantitative real-time polymerase chain reaction. Trigeminal ganglion cells were isolated from rabbits and cultured for 48 hours with or without PACAP27 (bioactive N-terminal peptide from PACAP). Cells were stained with antibody against neurofilaments, and neurite outgrowth was quantified by cell counting. In the rabbit LASIK model, a corneal flap with a planned thickness of 130 microm and 8.5 mm diameter was created with a microkeratome. The rabbits then received eyedrops containing PACAP27 four times a day for eight weeks, and corneal sensitivity was measured. Neurite outgrowth was assessed by staining histologic sections of the flap area for cholinesterase. RESULTS: The deduced amino acid sequence of PACAP in rabbit was identical to that of human. PACAP receptor, PAC1, was highly expressed in trigeminal ganglia from newborn and adult rabbits. PACAP27 at 1 microM induced growth of neuronal processes in cultured primary trigeminal ganglion cells. In the LASIK model, extensions of neuronal processes from amputated nerve trunks in cornea were observed after administration of eyedrops containing 1 or 10 microM PACAP27. The 10 microM PACAP27 treatment also greatly accelerated recovery of corneal sensitivity. CONCLUSIONS: PACAP may be a candidate drug for ameliorating dry eye after LASIK surgery.

Contribution of ROCK in contraction of trabecular meshwork: proposed mechanism for regulating aqueous outflow in monkey and human eyes.

Aqueous outflow in the conventional outflow pathway is regulated by the contraction and relaxation of the ciliary muscle (CM) and the trabecular meshwork (TM). Rho-associated coiled coil-forming protein kinase (ROCK) is thought to regulate actomyosin-based contractility in many types of cells by phosphorylation of ROCK substrates. In animal models, ROCK inhibitor Y-39983 relaxed CM and TM and decreased intraocular pressure (IOP). Thus, ROCK is implicated in the regulation of aqueous outflow and IOP. However, the site of action of ROCK in monkey and man is unknown. In the present communication, RT-PCR analysis of monkey tissues showed higher levels of mRNAs for ROCK and ROCK substrates in TM compared to CM. Human TM also showed higher levels of mRNAs for ROCK and ROCK substrates compared to CM. Differences between TM and CM in human were not as high as in monkey. ROCK inhibitor Y-39983 led to a dose-dependent relaxation of carbachol-induced, contracted TM from monkey. In contrast, Y-39983 was only slightly effective in relaxing CM. Our results suggested that TM was one of the major sites for regulating IOP by ROCK. ROCK inhibitor Y-39983 might be a candidate drug for lowering IOP by increasing conventional outflow and producing fewer side effects on accommodation and miosis.