D-Ser2-oxyntomodulin ameliorated Aß31-35-induced circadian rhythm disorder in mice.

INTRODUCTION: The occurrence of circadian rhythm disorder in patients with Alzheimer's disease (AD) is closely related to the abnormal deposition of amyloid-ß (Aß), and d-Ser2-oxyntomodulin (Oxy) is a protease-resistant oxyntomodulin analogue that has been shown to exert neuroprotective effects. AIMS: This study aimed to explore whether Oxy, a new GLP-1R/GCGR dual receptor agonist, can improve the Aß-induced disrupted circadian rhythm and the role of GLP-1R. METHODS: A mouse wheel-running experiment was performed to explore the circadian rhythm, and western blotting and real-time PCR were performed to assess the expression of the circadian clock genes Bmal1 and Per2. Furthermore, a lentivirus encoding an shGLP-1R-GFP-PURO was used to interfere with GLP-1R gene expression and so explore the role of GLP-1R. RESULTS: The present study has confirmed that Oxy could restore Aß31-35-induced circadian rhythm disorders and improve the abnormal expression of Bmal1 and Per2. After interfering the GLP-1R gene, we found that Oxy could not improve the Aß31-35-induced circadian rhythm disorder and abnormal expression of clock genes. CONCLUSION: This study demonstrated that Oxy could improve Aß31-35-induced circadian rhythm disorders, and GLP-1R plays a critical role. This study thus describes a novel target that may be potentially used in the treatment of AD.

[Six cases with Behcet's disease presenting cervical ulcer].

OBJECTIVE: To investigate the clinical feature and strategy on diagnosis and treatment of cervical ulcer in Behcet's disease. METHODS: From Jan 2000 to Apr 2008, the medical documents of 6 cases with cervical ulcer in Behcet's disease were reviewed retrospectively, who were treated in No.2 hospital affiliated to Wenzhou Medical School RESULTS: (1) General information: all 6 patients with cervical ulcer were diagnosed as Behcet's disease clinically, the mean age of all patients is 33.5 years. (2) CLINICAL FEATURE: the initial symptoms was oral ulcer in 5 cases and erythematic nodosum in 1 case. The typical characteristics of cervical ulcer in Behcet's disease was vaginal purulent discharge. Five among 6 cases presented it. The cervical ulcer in Behcet's disease exhibited the following features: the isolated well-defined ulcers with different size and different deep distributed on the uterine cervix, and the top of ulcer was covered by yellow discharge which was not easy to erase. The duration between the onset symptom and cervical ulcer was calculated to be 2.1 to 7 years. (3) Risk factors for cervical ulcer: operation of drawing intrauterine devices (IUD) in 2 cases, artifical abortion in 2 cases, cervical biopsy in 1 cases, and no factors in the other one case was identified. (4) TREATMENT: The cervical ulcer in Behcet's disease can be treated by the topical application of recombinant bovine basic fibroblast growth factor (rb-bFGF). If ulcer disease existing in other site, systemic corticosteroids management was warranted. (5) Recurrence: 1 case with recurrent disease was observed after 8 months when completing treatment, the other 5 cases did not show recurrence during 3 months-8 years follow-up. CONCLUSIONS: The cervical ulcer in Behcet's disease most commonly occurred after cervical operation. The diagnosis should be derived from comprehensive symptoms analysis. The topical application of rb-bFGF on ulcer site of cervix could get satisfied outcome. When necessary, systemic corticosteroids administration could be considered.