Histomorphometric evaluation of the effect of systemic and topical ozone on alveolar bone healing following tooth extraction in rats.

The aim of this study was to investigate the effects of systemic and topical ozone applications on alveolar bone healing following tooth extraction. One hundred and twelve male Wistar rats were divided into eight groups of 14 rats each; seven groups were experimental (A-G) and one formed the control group (K). The experimental groups were further divided into two sub-groups, with seven rats in each - sacrificed on days 14 and 28 (subgroups 1 and 2). The maxillary right central incisors were extracted under general anaesthesia following the administration of local anaesthesia. After sacrifice, semi-serial histological sections were prepared, and mineralized and trabecular bone and osteoid and osteoblast surfaces were measured. Measurements of the trabecular bone showed statistically higher values in the groups treated with systemic ozone (D(2): 50.01 ± 2.12; E(2): 49.03 ± 3.03; F(2): 48.76 ± 2.61; G(2): 50.24 ± 3.37) than in the groups that underwent topical ozone administration (A(2): 46.01 ± 3.07; B(2): 46.79 ± 3.09; C(2): 47.07 ± 2.12; P = 0.030 (G(2)-A(2), G(2)-B(2), G(2)-C(2))). Within the limitations of the current study, it may be concluded that postoperative long-term systemic ozone application can accelerate alveolar bone healing following extraction. However, additional studies are required to clarify the effects of the different ozone applications on new bone formation.

Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation.

Cyclophosphamide (CP) and ifosfamide (IF) are widely used antineoplastic agents, but their side-effect of hemorrhagic cystitis (HC) is still encountered as an important problem. Acrolein is the main molecule responsible of this side-effect and mesna (2-mercaptoethane sulfonate) is the commonly used preventive agent. Mesna binds acrolein and prevent its direct contact with uroepithelium. Current knowledge provides information about the pathophysiological mechanism of HC: several transcription factors and cytokines, free radicals and non-radical reactive molecules, as well as poly(adenosine diphosphate-ribose) polymerase (PARP) activation are now known to take part in its pathogenesis. There is no doubt that HC is an inflammatory process, including when caused by CP. Thus, many cytokines such as tumor necrosis factor (TNF) and the interleukin (IL) family and transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) also play a role in its pathogenesis. When these molecular factors are taken into account, pathogenesis of CP-induced bladder toxicity can be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial cells; (2) it then activates intracellular reactive oxygen species and nitric oxide production (directly or through NF-kappaB and AP-1) leading to peroxynitrite production; (3) finally, the increased peroxynitrite level damages lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks) leading to activation of PARP, a DNA repair enzyme. DNA damage causes PARP overactivation, resulting in the depletion of oxidized nicotinamide-adenine dinucleotide and adenosine triphosphate, and consequently in necrotic cell death. For more effective prevention against HC, all pathophysiological mechanisms must be taken into consideration.

Hyperbaric oxygen treatment time for cyclophosphamide induced cystitis in rats.

The aim of this study was to evaluate the prophylactic potential of hyperbaric oxygenation treatment and the timing of hyperbaric oxygen (HBO2) therapy for cyclophosphamide-(CYP) induced cystitis in rats. Forty male Sprague-Dawley rats were divided into 5 groups. Four groups received a single dose of CYP (100 mg/kg.) intraperitoneally (i.p.) at the same time (group 1 served as the control). Group 2 received CYP only; group 3 received HBO2 treatment (2.8 atmospheres absolute, 90 minutes, twice daily) before and the day after CYP. Group 4 received HBO2 before and on the day of CYP administration. Group 5 received HBO2 on the day of and the day after CYP. CYP injection resulted in severe cystitis. Prophylactic HBO2 treatment did not prevent the severe cystitis. After CYP injection, however, HBO2 treatment attenuated CYP-induced hemorrhagic cystitis in rats. Hyperbaric oxygen has a beneficial effect on repairing and healing bladder damage, though it does not function to prevent CYP-induced hemorrhagic cystitis.

Prevention of further cyclophosphamide induced hemorrhagic cystitis by hyperbaric oxygen and mesna in guinea pigs.

PURPOSE: Hyperbaric oxygen therapy and mesna have been successfully used for hemorrhagic cystitis. We defined the protective effects of hyperbaric oxygen and mesna in further cyclophosphamide induced hemorrhagic cystitis in guinea pigs. MATERIALS AND METHODS: A total of 48 male guinea pigs were divided into 6 groups. All groups received 2 doses of 68.1 mg./kg. cyclophosphamide intraperitoneally at the same time intervals but group 1 served as controls. Group 2 received cyclophosphamide only, group 3 received hyperbaric oxygen treatment (2.8 ATA for 90 minutes twice daily) before and the day after further cyclophosphamide, group 4 received 21.5 mg./kg. mesna intraperitoneally only with further cyclophosphamide, group 5 received hyperbaric oxygen and mesna with further cyclophosphamide, and group 6 received hyperbaric oxygen before initial cyclophosphamide, between the 2 doses and after the further dose of cyclophosphamide, and mesna on the days of cyclophosphamide. RESULTS: Although mesna alone provided protection against cyclophosphamide induced cystitis in animal bladders, there was also significant damage compared with controls. When the uroprotective efficacy of mesna was supported with hyperbaric oxygen, bladder protection was promoted since mean histological scores and hematuria levels in this group did not differ from those in controls. CONCLUSIONS: According to this animal study using hyperbaric oxygen as adjuvant therapy in humans may be a better tool than mesna alone for the prophylaxis and treatment of cyclophosphamide induced hemorrhagic cystitis.