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    Biological rhythm of saliva ghrelin in humans
    (Taylor & Francis Ltd, 2006) Aydin, Suleyman; Ozercan, H. Ibrahim; Aydin, Suna; Ozkan, Yusuf; Dagli, Ferda; Oguzoncul, Ferdane; Geckil, Hikmet
    Background: We previously reported that ghrelin in saliva, orexigenic hormone that induces NPY release, was produced and released by salivary glands in humans. The purpose of this study was to investigate a possible circadian rhythm in saliva ghrelin concentration in human subjects as a function of time and meal. Saliva samples were collected at three-hour intervals throughout a 24-h period in 12 healthy volunteer males and ten healthy volunteer females who were provided with meals on a fixed schedule, and saliva collections were made within 15 minutes after each meal. Saliva ghrelin levels were measured by using a commercial radioimmuno assay (RIA) kit that uses I-125-labeled bioactive ghrelin as a tracer and a rabbit polyclonal antibody raised against full-length octanoylated human ghrelin. Immunohistochemical analysis of salivary glands was also performed. The results of this investigation indicated the following. (1) The saliva ghrelin level was slightly higher in female subjects in comparison with male subjects. (2) Saliva ghrelin levels were elevated before each meal and fell to trough levels after eating. (3) Saliva ghrelin levels showed a circadian rhythm that rose throughout the day to a zenith at 0300, then dropped at 0600-0900. (4) Saliva ghrelin also weakly correlated with BMI. (5) Immunohistochemical analysis showed that ghrelin was localized in the striated and excretory ducts of salivary glands of human. The present work is the first report of the circadian rhythm of saliva ghrelin level in human subjects as a function of time and meal. Meal plays an important role in lowering saliva ghrelin concentration in humans. However, present data did not exclude whether the circadian changes in saliva ghrelin expression were regulated by the biological clock or by food intake.
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    The comparison of the impact of ghrelin and tacrolimus on vitreous cytokine levels in an experimental uveitis model
    (Springer, 2013) Gul, Fatih Cem; Turgut, Burak; Dagli, Ferda; Ilhan, Nevin; Ozgen, Metin
    We aimed to compare the effects of intraperitoneal ghrelin and tacrolimus on vitreous levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) in an experimental autoimmune uveitis model. Twenty-four male rats, each weighing 300 g, were assigned into four groups, six rats in each. All the rats, except for those in group 1, were injected intravitreally with concanavalin a to induce experimental uveitis. The development of uveitis was confirmed by the histopathologic examination of two rat globes from each group. The rats in group 2 were not given any treatment after uveitis was induced. The rats in group 3 were administered 1 mg/kg/day of intraperitoneal tacrolimus on days 0, 1, 3, 5 and 7 following the induction of uveitis (on the 14th day of study). The rats in group 4 were given 10 ng/kg/day of intraperitoneal ghrelin for 7 days following the induction of uveitis. On the 21st day of the study, all rats were sacrificed, and the eyes enucleated were subjected to histopathologic examination. Vitreous levels of TNF-alpha, IL-1 and IL-6 were measured by the enzyme-linked immunosorbent assay method. The histopathologic evaluation carried out to confirm the development of uveitis revealed destruction in the retinae and ciliary bodies of the immunized rats. The mean vitreous levels of TNF-alpha, IL-1 and IL-6 were significantly higher in the sham group than in the control group (p < 0.05). The levels of these three cytokines showed a significant decrease in the tacrolimus treatment group (p < 0.05). Cytokine levels decreased in the ghrelin treatment group relative to the control group; however, the decrease was not found statistically significant (p > 0.05). Tacrolimus could be effective in uveitis treatment by neutralizing or decreasing the levels of cytokines such as TNF-alpha, IL-1 and IL-6 that have a critical part in the pathogenesis of uveitis. However, ghrelin failed to produce the desired effect. Further studies using different doses and different ways of administration are needed to determine the effective dose of ghrelin in uveitis.
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    Impact of ghrelin on vitreous cytokine levels in an experimental uveitis model
    (Dove Medical Press Ltd, 2013) Turgut, Burak; Gul, Fatih Cem; Dagli, Ferda; Ilhan, Nevin; Ozgen, Metin
    Background: The purpose of this study was to investigate the effect of intraperitoneal ghrelin on vitreous levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) and to compare its effects with those of intraperitoneal infliximab in an experimental uveitis model. Methods: Twenty-four male rats were assigned to four groups of six rats in each. All the rats, except for those in group 1 (controls), were injected intravitreally with concanavalin A to induce experimental uveitis. Rats in group 2 (sham) were not given any treatment after uveitis was induced. Rats in group 3 were given intraperitoneal infliximab 0.5 mg/100 mL on days 0, 1, 3, 5, and 7 following induction of uveitis on day 14 of the study. Rats in group 4 were given intraperitoneal ghrelin 10 ng/kg/day for 7 days following induction of uveitis. On day 21 of the study, enucleated globes were subjected to histopathologic examination. Vitreous levels of IL-1, IL-6, and TNF-alpha were measured by enzyme-linked immunosorbent assay. Results: Vitreous levels of IL-1, IL-6, and TNF-alpha were significantly increased in the sham group relative to the control group (P < 0.05), but showed a significant decrease in the group treated with infliximab (P < 0.05). Cytokine levels also decreased in the ghrelin-treated group, but the decrease was not statistically significant (P > 0.05). Conclusion: Ghrelin failed to decrease the IL-1, IL-6, and TNF-alpha levels that play a critical role in the pathogenesis of uveitis.