The effect of topical doxycycline in the prevention of experimental tympanosclerosis.

OBJECTIVES: The aim of this study is to determine the effectiveness of topical doxycycline used in the process of experimental myringosclerosis and tympanosclerosis. STUDY DESIGN: A prospective experimental animal study. METHODS: Experimental tympanosclerosis was accomplished in 25 healthy adult guinea pigs by inoculation with 2.5 x 10(7) colony-forming units of type-3 Streptococcus pneumoniae microorganisms followed by bilateral myringotomy. While the animals' right ears received a topical doxycycline treatment daily, their left ears were left untreated and used as controls. Otomicroscopic examination was carried out weekly and healing tympanic membranes were remyringotomized. After a 6-week follow-up, the temporal bones of 24 of 25 animals were removed and light-microscopy examination was done regarding tympanic membrane myringosclerosis and middle ear mucosal sclerosis. RESULTS: Myringosclerosis was noticed to a lesser extent in the doxycycline-treated group when compared to the untreated control group. Light microscopy evaluation revealed a difference in the area and thickness of the sclerotic plaques of myringosclerosis of the tympanic membranes in the doxycycline-treated group and the control group, being significantly smaller and thinner in the treated group (P < .001, P < .04, respectively). Similarly, the area and thickness of the sclerotic plaques in the middle ear mucosa were significantly smaller and thinner in the doxycycline treated group (P < .001, P < .03). CONCLUSION: This study demonstrated that the potent matrix metallo-proteinase inhibitor doxycycline plays a preventive role in the development of experimentally induced tympanosclerosis.

Effects of chronic treatment with valproate and oxcarbazepine on ovarian folliculogenesis in rats.

PURPOSE: We aimed to define the morphologic effects of valproate (VPA) and oxcarbazepine (OXC) on ovarian folliculogenesis in rats. METHODS: Forty female wistar rats (21-24 days old and weighted between 46.4 and 55.3 g) were divided equally into 4 experimental groups, which were applied tap water (control group), 300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90 days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle according to daily vaginal smear were taken out and placed in a fixation solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were applied. RESULTS: The number of follicles decreased and that of corpora lutea increased significantly in OXC, VPA, and OXC+VPA treated groups compared with control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40 +/- 0.52 in control group, but it significantly increased to 3.50 +/- 0.53, 3.50 +/- 0.53, and 4.90 +/- 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The increase in the number of TUNEL positive granulosa cells was also significant for OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGF beta 1 and IGF1 staining and increased for P53 staining in all drug groups compared with control group (p < 0.001). Intensity of P53 labeling increased, while intensity of TGF beta 1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group (p < 0.001). CONCLUSION: Long-term treatment with VPA or OXC from prepuberty to adulthood causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.