The death of one cell can precipitate the death of nearby cells in a process referred to as the bystander effect. We investigated whether mitochondrial apoptosis generated a bystander effect and, if so, by which pathway. Microinjection with cytochrome c mimicked function of the mitochondrial apoptosis-induced channel MAC and caused apoptosis of both target and nearby osteoblasts. This effect was suppressed by inhibiting gap junction intercellular communication. A bystander effect was also observed after exogenous expression of tBid, which facilitates MAC formation and cytochrome c release. Interestingly, in connexin-43 deficient osteoblasts, microinjection of cytochrome c induced apoptosis only in the target cell. These findings indicate that a death signal was generated downstream of MAC function and was transmitted through gap junctions to amplify apoptosis in neighboring cells. This concept may have implications in development of new therapeutic approaches.

Objectives:The objective of this study is to analyze the hard and soft-tissue profile changes as well as the upper airway changes after distraction osteogenesis (DO) using rigid external distraction device in adult cleft lip and palate (CLP) patients. The study also evaluates the stability of the surgical result.Materials and Methods:Three lateral cephalometric radiographs were taken: Predistraction (T1), postdistraction (T2), and 1 year after distractor removal (T3). The treatment changes (T1 vs. T2) and the stability (T2 vs. T3) were analyzed. The overall treatment changes after 1 year were also evaluated (T1 vs. T3). The lateral cephalograms were digitally analyzed with the help of software named Dolphin.Statistical Analysis Used:Wilcoxon Signed-Ranks test was used, and the probability value (P value) of 0.05 was considered as statistically significant level.Results:Eleven adult patients with CLP were retrospectively analyzed. After distraction, there was a significant mean maxillary advancement of 14 mm (P < 0.01) from a T1 value of 73.54 ± 10.38 to a T2 value of 88.2 ± 10.49. The lower facial height and the incisor exposure were significantly increased. The nasolabial angle had a significant improvement of 24.5° (P < 0.01) from a T1 value of 56.6 ± 21.03 to a T2 value of 81.18 ± 14.4.The upper airway was significantly improved by 3.7 mm (P < 0.01) with a T1 value of 13.5 ± 3.8 to a T2 value of 17.2 ± 3.66. After 1-year follow-up, there was a significant maxillary relapse of 3.20 mm (P < 0.05) from a T2 value of 8.29 ± 6.84 to a T3 value of 5.09 ± 5.59. However, the soft-tissue profile and upper airway remained stable.Conclusion:The clinician should have an understanding of the related hard and soft tissues as well as airway changes which may assist him when planning for maxillary advancement for CLP patients with DO. There were significant improvements immediately after distraction, but during the 1-year follow-up, some relapse was seen. This stressed on the need for overcorrection of about 35%–40% for adult CLP patients.

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