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Made available in DSpace on 2022-05-01T09:47:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background and objective: The interaction between antineoplastic drugs used for treating cancer and non-affected tissues remains poorly assessed and may be critical for maintaining the quality of life for patients during and after treatment. This pre-clinical study evaluated the effects of cisplatin (CIS) and 5-fluorouracil (5-FU) on the peri-implant repair process around osseointegrated titanium implants installed in the tibiae of rats. Material and methods: Were used 90 male rats, randomly divided into three groups (n = 30): physiological saline solution (PSS), CIS, and 5-FU. Titanium implants (4.0 × 2.2 mm) were inserted in both tibiae of all animals at day 0. The animals received either PSS, CIS, or 5-FU at 35 and 37 days. Euthanasia was performed at 50, 65, and 95 days after surgery. Histometric (bone/implant contact [BIC]) and bone area fraction occupancy (% BAFO), histological, and immunohistochemical (for bone morphogenetic protein 2/4 [BMP2/4], Runt-related transcription factor 2 [RUNX2], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. Data were statistically analyzed. Results: Groups CIS and 5-FU presented lower BIC and lower BAFO as compared with PSS in all time points. The imbalance in bone turnover was observed by the lower number of BMP2/4-, RUNX2-, and OCN-positive cells/mm2 and the higher number of TRAP-positive cells/mm in groups CIS and 5-FU as compared with PSS in all time points. Persistent and exacerbated inflammation was observed in groups CIS and 5-FU. Conclusions: Both antineoplastic agents interfered negatively in the bone turnover around osseointegrated titanium implants. Clinical relevance: Closer and more careful follow-up of patients with osseointegrated implants that will undergo chemotherapy with either CIS or 5-FU shall be performed. Department of Diagnosis and Surgery–Periodontics Division São Paulo State University (Unesp), St. José Bonifácio 1193 - Vila Mendonça, SP Nucleus of Study and Research in Periodontics and Implantology (NEPPI) School of Dentistry São Paulo State University (Unesp), SP Department of Basic Science School of Dentistry São Paulo State University (Unesp), SP Department of Diagnosis and Surgery–Periodontics Division São Paulo State University (Unesp), St. José Bonifácio 1193 - Vila Mendonça, SP Nucleus of Study and Research in Periodontics and Implantology (NEPPI) School of Dentistry São Paulo State University (Unesp), SP Department of Basic Science School of Dentistry São Paulo State University (Unesp), SP FAPESP: 2014/11427-8 FAPESP: 2017/11805-0

To assess the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the treatment of cancer. This study evaluated the influence of cisplatin (CIS) and 5-fluorouracil (5-FU) over the peri-implant tissues around osseointegrated titanium implants in animals previously exposed to nicotine. Materials and methods One hundred twenty male rats were divided into two groups, receiving via subcutaneous injection, either physiological saline solution (PSS) (n = 30) or nicotine hemissulfate (NIC) (n = 90) for 30 days prior to implants' placement. One titanium implant (4.0 × 2.2 mm) was installed in each tibia of all animals. PSS and NIC were continued for 30 days after surgery. Five days after cessation, rats were subdivided into three subgroups in accordance with systemic treatments with either PSS, CIS, or 5-FU. Euthanasia was performed at 50, 65, and 95 days post-surgery. Histometric, histopathological, and immunohistochemical analyses were performed.NIC-CIS and NIC-5FU presented lower BIC (50, 65, and 95 days) and bone area fraction occupancy (BAFO) (65 and 95 days) than group NIC. Intense inflammatory infiltration, severe tissue breakdown, reduced expression of bone formation biomarkers, and upregulation of TRAP were observed in NIC-CIS and NIC-5FU when compared with group NIC. TRAP expression was significantly higher in NIC-5FU as compared with NIC-CIS at 50 and 95 days. Groups NIC, NIC-CIS, and NIC-5FU presented statistically significant negative impact in all outcome parameters than group PSS.CIS and 5-FU severely disrupted the peri-implant tissues around osseointegrated implants in animals previously exposed to nicotine.Assessing the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the cancer treatment.

Nifedipine is a calcium channel blocker dihydropyridine that has been used in the treatment of hypertension. The production of reactive species and calcium overload are the main contributors to myocardial ischemia-reperfusion (I / R) injury. We investigated the ability of novel dihydropyridines (DHPs) to improve the effect of protecting against the injury induced by ischemia and reperfusion in cardioblasts when compared to nifedipine. Forty three DHPs were created varying the fatty chains derived from palmitic acid, stearic acid and oleic acids and aromatic moiety in addition to the addition of chemical elements such as chlorine, nitrogen dioxide, furfural, hydroxyl and methoxy. Cytotoxicity and inhibition of linoleic oxidation were evaluated for all new DHPs and also for nifedipine. The alpha-tocopherol and butylated hydroxytoluene (BHT) were used as antioxidants controls. The compounds with the best antioxidant potential were used in the ischemia and reperfusion (I / R) induction test in cardioblasts (H9c2). Cardioblasts were treated 24 h after assembly of plates and submitted to the ischemia simulation (30 min), after which, normoxia and cellular nutrition conditions were reestablished, simulating reperfusion (additional 30 min). Right after, cell viability, apoptosis, necrosis, and the generation of reactive oxygen species (ROS) were evaluated. Cell viability during I / R was not altered in cells treated with nifedipine, BHT and the new DHP composed of palmitic acid with hydroxyl group in the aromatic substituent. The other new DHPs increased cell viability during I / R simulation and reduced levels of reactive species compared to the I / R group, demonstrating the antioxidant capacity of the new DHPs. Therefore, DHPS with palmitic and oleic acids in the C3 and C5 position with NO2 or Cl in aromatic moiety, presented the highest antioxidant potential (linoleic oxidant test). The new DHPs increased cell viability during I / R simulation and reduced levels of reactive species compared to the ischemia and reperfusion group, demonstrating the antioxidant capacity of the new DHPs. Taken together, these results indicate that those new DHPs have a greater cardioprotective antioxidant capacity to face the damages of ischemia and reperfusion.

Made available in DSpace on 2021-06-25T11:09:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Background: This study is designed to evaluate the potential of different formulations of hyaluronic acid (HA) to improve new bone formation in critical-size calvaria defect (CSD) when combined with a deproteinized bovine graft (DBG) material. Methods: Thirty male rats were used. A 5-mm-diameter CSD was created and three experimental groups (n = 10) were randomly assigned based on the treatments performed. Group DBG: CSD filled with a DBG; group DBG/LV: CSD filled by the combination of DBG and HA in a low-viscosity crosslinking agent; group DBG/HV: CSD filled by the combination of DBG and HA in a high-viscosity crosslinking agent. Animals were euthanized 30 days postoperatively. Histological, histometric (percentage of newly formed bone [PNFB], percentage of remaining graft particles, histochemical, and immunohistochemical (bone morphogenetic protein 2/4 [BMP2/4], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. Results: The highest PNFB was observed in DBG/HV when compared with the other groups (P ≤0.05). DBG/LV and DBG/HV presented almost no inflammatory cells. In contrast, inflammation was observed in group DBG. Extensive resorption of graft particles was observed in group DBG, which was not present in DBG/LV and DBG/HV as confirmed by the larger size of the particles (P ≤0.05). BMP2/4 and OCN immunolabeling were higher in DBG/HV when compared with group DBG (P ≤0.05). Increased number of TRAP-positive cells was observed in DBG/LV and DBG/HV (P ≤0.05). Lower percentage of mature collagen fibers was observed in DBG/HV (P ≤0.05). Conclusion: The combination of HA in a high-viscosity crosslinking agent with DBG improves the bone repair process and increases the amount of newly formed bone towards CSDs in rat calvaria. Department of Diagnosis and Surgery‒Periodontics Division School of Dentistry São Paulo State University (UNESP) Department of Basic Science School of Dentistry São Paulo State University (UNESP) Private practice. Director of the Pro-clinic Nucleus of Orofacial Harmonization Department of Diagnosis and Surgery‒Periodontics Division School of Dentistry São Paulo State University (UNESP) Department of Basic Science School of Dentistry São Paulo State University (UNESP)

Made available in DSpace on 2022-04-28T19:46:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background. The potent anti-inflammatory and immunosuppressive properties of glucocorticoids (GCs) might influence the progression of some disorders, such as periodontitis. Hence, this study aimed to investigate the influence of dexamethasone (DEX) on the alveolar bone loss (ABL) of healthy and periodontally compromised molars in rats. Methods. Thirty male rats were randomly assigned to two groups: physiological saline solution (PSS) and DEX. The animals received subcutaneous injections of either 0.5 mL of PSS) (group PSS) or 2 mg/kg of DEX (group DEX) from one day before experimental periodontitis (EP) induction until euthanasia. EP was induced through ligature placement around the mandibular lower first molars at day 0. Contralateral molars remained unligated. Ten animals per period were euthanized on days 3, 7, and 14. Morphometric analysis was performed to access the ABL. Data were statistically analyzed with ANOVA followed by post hoc Tukey tests (P ≤ 0.05). Results. Higher ABL was observed in both groups on days 7 and 14 than on day 3 (P ≤ 0.05). Concerning periodontitis, higher ABL was observed in group DEX on days 3, 7, and 14 days than group PSS at the same time intervals (P ≤ 0.05). Also, even in the contralateral unligated molars, group DEX exhibited higher ABL on days 3, 7, and 14 days than group PSS at the same time intervals (P ≤ 0.05). Conclusions. Collectively, it can be concluded that DEX aggravates EP and induces spontaneous ABL in the healthy periodontium. Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry

Aim This study evaluated the effects of 5-fluorouracil (5-FU) and cisplatin (CIS) in healthy periodontal tissues and in the early stages of experimental periodontitis (EP) in rats. Methods One hundred and eighty male rats were divided into three groups, which were submitted to the following systemic treatments: physiological saline solution (PSS); CIS and 5FU. Each group was subdivided into two subgroups: without (NEP) and with (EP) induction of EP. Animals were euthanized at 3, 5 and 7 days post-treatment. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (for tumour necrosis factor-α, interleukin-1β and receptor activator of nuclear factor-κB ligand) analyses were performed. Data were statistically analysed. Results CIS-NEP and 5FU-NEP showed more inflammation than PSS-NEP at 3, 5 and 7 days. CIS-EP and 5FU-EP showed more inflammation and lower PBF than PSS-EP at all periods of evaluation. 5FU-EP showed lower PBF than CIS-EP at 5 and 7 days. Conclusion 5-FU and CIS exacerbated periodontal inflammation and aggravated the progression of EP in its early stages.

Made available in DSpace on 2018-12-11T17:12:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Objective: The aim of this study was to investigate the biocompatibility of methylene blue at different pH levels through the method of implantation in subcutaneous tissue. Materials and methods: Eighty-four sterilized polyethylene tubes were allocated in the subcutaneous tissue of 28 rats, each one receiving four tubes, set into four groups: group tube (G-T)—empty tube, fibrin group (G-F)—tube filled with fibrin sponge, group methylene blue pH 7 (G-MB/pH 7)—tube filled with fibrin sponge soaked by methylene blue (100 μg/ml) at pH 7.0, and group methylene blue pH 1 (G-MB/pH 1)—tube filled with fibrin sponge and soaked by methylene blue (100 μg/ml) at pH 1.0. After 7, 15, and 30 days, seven animals from each group were euthanized, and the tubes involved by the surrounding tissue were removed and fixed with 4% buffered formaldehyde solution. The collected pieces were processed and histological sections (4 μm) were stained with hematoxylin and eosin and analyzed by light microscopy. Scores were assigned to analysis of histopathologic parameters. The results were statistically analyzed by the Kruskal–Wallis test (p ≤ 0.05). Results: At 7 and 30 days, the G-MB/pH 1 group showed no significant difference in the G-T control group, while G-MB/pH 7 had a significant increase on tissue reaction, also when compared to G-T. At 15 days, there was no statistical difference between the groups. Conclusion: Within the limits of this study, it is concluded that methylene blue at pH 1.0 provides better biocompatibility than at pH 7.0. Department of Surgery and Integrated Clinic Division of Periodontics São Paulo State University (Unesp) School of Dentistry, Araçatuba - R. José Bonifácio, 1193 Department of Endodontics São Paulo State University (Unesp) School of Dentistry, Araçatuba - R. José Bonifácio, 1193 Department of Surgery and Integrated Clinic Division of Periodontics São Paulo State University (Unesp) School of Dentistry, Araçatuba - R. José Bonifácio, 1193 Department of Endodontics São Paulo State University (Unesp) School of Dentistry, Araçatuba - R. José Bonifácio, 1193

Made available in DSpace on 2018-12-11T17:08:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-01 Objective To analyze the influence of low-level laser therapy (LLLT) on the bone healing process of autogenous bone block grafts installed in nicotine systemically modified rats. Methods Seventy-two rats (Wistar) were randomly assigned into 4 groups (n = 18). SS-BG: saline application + bone graft. SS-BG/LLLT: saline application + bone graft + LLLT. NIC-BG: nicotine application + bone graft. NIC-BG/LLLT: nicotine application + bone graft + LLLT. After 30 days of application of solutions, all animals received autogenous bone block graft in the jaw, with the donation from the parietal bone's calvarial area. Treatment with LLLT was in bed-graft interface, after accommodation of the graft. The animals in each group were sacrificed at 7, 14, and 28 days after graft surgery. Results The histologic analyses of NIC-BG group depicted a delay of osteogenic activity in the recipient bed-graft interface and the irradiation of tissue with LLLT provided better bone healing. The histometric analysis revealed that SS-BG/LLLT and NIC-BG/LLLT groups showed increased bone formation compared to BG-SS and NIC-BG groups, after 14 days (SS-BG 24.94% ± 13.06% versus SS-BG/LLLT 27.53% ± 19.07% and NIC-BG 14.27% ± 2.22% versus NIC-BG/LLLT 24.37% ± 11.93%) and 28 days (SS-BG 50.31% ± 2.69% versus SS-BG/LLLT 58 19% ± 12.32% and NIC-BG 36.89% ± 8.40% versus NIC-BG/LLLT 45.81% ± 6.03%). Conclusion Nicotine harms bone formation in the bed-graft interface and LLLT action can mitigate this. Univ. Estadual Paulista-UNESP Division of Periodontics Department of Surgery and Integrated Clinic Dental School of Araçatuba, Rua José Bonifácio, n° 1193, São Paulo Univ. Estadual Paulista-UNESP Division of Periodontics Department of Surgery and Integrated Clinic Dental School of Araçatuba, Rua José Bonifácio, n° 1193, São Paulo