ABSTRACT
Nesfatin-1, a satiety molecule processed from nucleobindin2 (NUCB2), is implicated in visceral hypersensitivity in rats and colocalized with 5-hydroxytryptamine (5-HT) in the dorsal raphe nucleus (DRN). Maternal separation (MS) in rats contributes to visceral hypersensitivity via elevated expression of 5-HT in the DRN. Intracerebroventricular injection of nesfatin-1 activates DRN 5-HT neurons. In this study, A model of visceral hypersensitivity was developed by subjecting rats to MS. Colorectal distension was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR) scores and electromyogram (EMG) magnitude. MS rats exhibited higher AWR scores and EMG magnitude compared with controls. The numbers of nesfatin-1- and tryptophan hydroxylase (TPH, the rate-limiting enzyme for 5-HT synthesis)-positive cells in the DRN were significantly elevated accordingly. Visceral hypersensitivity was significantly alleviated in MS rats treated with intra-DRN administration of anti-nesfatin-1/NUCB2, accompanied by decreased expression of 5-HT and TPH in the DRN, compared with the vehicle-treated group. In contrast, intra-DRN administration of nesfatin-1 into normal adult rats induced visceral hypersensitivity, which correlated with elevated expression of 5-HT and TPH in the DRN. In conclusion, Nesfatin-1 has critical effects on visceral hypersensitivity; the underlying mechanisms might be related to the activation of DRN 5-HT neurons.
Subject(s)
Calcium-Binding Proteins/metabolism , DNA-Binding Proteins/metabolism , Dorsal Raphe Nucleus/metabolism , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Serotonin/metabolism , Animals , Electromyography , Female , Immunohistochemistry , Male , Nucleobindins , Pregnancy , Rats , Tryptophan Hydroxylase/metabolismABSTRACT
OBJECTIVE: This study aims to explore the rule of changes in serum GGT activity, as well as GGT/ALT and AST/ALT ratios, in primary hepatic carcinoma (PHC) patients with different alpha-fetal protein (AFP) levels. METHODS: GGT, AST and ALT were detected in 370 PHC patients with positive HBs-Ag using a automatic biochemical analyzer, and AFP was detected using a Roche E170 modular analytics immunoassay analyzer. GGT level, as well as AST/ALT and GGT/ALT, ratios were compared among PHC patients with different AFP levels. RESULTS: As shown in Table 1, GGT levels were 109.59 ± 111.06, 151.13 ± 190.43, 135.86 ± 107.62, 151.36 ± 176.59 and 172.58 ± 188.84, respectively, in the groups of primary PHC patients with AFP levels of ⩽ 10, 10-100, 100-200, 200-400 and ⩾ 400 ng/ml; and the differences among these groups were not statistically significant (P> 0.05). AST/ALT ratios were 1.55 ± 1.02, 1.30 ± 0.81, 2.02 ± 1.89, 2.12 ± 1.11 and 1.73 ± 1.25, respectively; and the differences among these groups were not statistically significant (P> 0.05). GGT/ALT ratios were 3.43 ± 3.12, 3.57 ± 5.70, 3.57 ± 2.94, 3.89 ± 4.58 and 3.43 ± 3.61, respectively; and the differences among these groups were not statistically significant (P> 0.05). CONCLUSION: For patients with chronic hepatitis B and cirrhosis after hepatitis B, no matter how AFP level is, when liver function report reveals increased GGT, AST/ALT > 1 and GGT/ALT > 1 (that is, AST > ALT and GGT > ALT), even if AFP is negative, we should also be alert to the existence of PHC.
