Periodontal disease is that condition resulting in the destruction of periodontal tissues, bone resorption, and tooth loss, the etiology of which is linked to immunological and microbiological factors. The aim of this study was to evaluate the potential trigger of periodontal disease in a rat model using bacterial species incriminated in the pathology of human periodontitis and to establish their optimal concentrations capable of reproducing the disease, with the idea of subsequently developing innovative treatments for the condition. In this study, we included 15 male Wistar rats, aged 20 weeks, which we divided into three groups. In each group, we applied ligatures with gingival retraction wire on the maxillary incisors. The ligature and the gingival sac were contaminated by oral gavage with a mixture of fresh cultures of Aggregatibacter actinomycetemcomitans (A.a), Fusobacterium nucleatum (F.n) and Streptococcus oralis (S.o) in concentrations of 108, 109, and 1010 CFU/mL each for 5 days a week for 4 weeks. During the clinical monitoring period of 28 days, overlapped with the period of oral contamination, we followed the expression of clinical signs specific to periodontitis. We also monitored the evolution of body weight and took weekly samples from the oral cavity for the microbiological identification of the tested bacteria and blood samples for hematological examination. At the end of the study, the animals were euthanized, and the ligated incisors were taken for histopathological analysis. The characteristic symptomatology of periodontal disease was expressed from the first week of the study and was maintained until the end, and we were able to identify the bacteria during each examination. Hematologically, the number of neutrophils decreased dramatically (p < 0.0001) in the case of the 109 group, unlike the other groups, as did the number of lymphocytes. Histopathologically, we identified neutrophilic infiltrate in all groups, as well as the presence of coccobacilli, periodontal tissue hyperplasia, and periodontal lysis. In the 109 group, we also observed pulpal tissue with necrotic bone fragments and pyogranulomatous inflammatory reaction. By corroborating the data, we can conclude that for the development of periodontal disease using A.a, F.n, and S.o, a concentration of 109 or 1010 CFU/mL is required, which must necessarily contaminate a ligature thread applied to the level of the rat’s dental pack.

Periodontal disease is that condition resulting in the destruction of periodontal tissues, bone re-sorption and tooth loss, the etiology of which is linked to immunological and microbiological factors. The aim of the study is to evaluate the potential trigger of periodontal disease in a rat model using the bacterial species incriminated in the pathology of human periodontitis and to establish their optimal concentration capable of reproducing the disease, with the idea of subsequently devel-oping innovative treatments for the condition. We included in the study 15 male Wistar rats, aged 20 weeks, which we divided into three groups. In each group, we applied ligatures with gingival retraction wire, on the maxillary incisors. 4 days/week, 4 weeks, the ligature and the gingival sac were contaminated with fresh cultures of Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis in concentrations of 108, 109 and 1010CFU/ml. The clinical monitoring period was 28 days, during which we followed the expression of clinical signs specific to periodontitis, the evolution of body weight and we took weekly samples from the oral cavity for the microbiological identification of the tested bacteria and blood samples for the hematological examination. At the end of the study, the animals were euthanized and the ligated incisors were taken for histopathological analysis. The characteristic symptomatology of periodontal disease was expressed from the first week of the study and was maintained until the end, the bacteria being able to be identified at each examina-tion. Hematologically, the number of neutrophils decreased dramatically (P&lt;0.0001) in the case of group 109, unlike the other groups, as did the number of lymphocytes. Histopathologically, we identified neutrophilic infiltrate in all groups. The presence of coccobacilli, periodontal tissue hyperplasia and periodontal lysis, but in group 109 we also observed pulpal tissue with necrotic bone fragments and pyogranulomatous inflammatory reaction. By corroborating the data, we can conclude that for the development of periodontal disease using A.a, F.n and S.o, a concentration of 109 or 1010CFU/ml is required, which must necessarily con-taminate a ligature thread applied to the level of the rat&#039;s dental pack.

"SARS-CoV-2 infection increases the risk of multi-organ systemic complications and venous and arterial thromboembolism. The development of vaccines has proven to be an effective method to combat severe forms of infection. Adverse effects reported after COVID-19 vaccination consisted of local injection site reaction, fatigue, myalgia, or fever as well as sporadic cases of vaccine-induced thrombotic immune thrombocytopenia, especially viral vector vaccines. Objectives: The aim of the study was to evaluate the repeated dose toxicity of a candidate vaccine against SARS-CoV-2, a test in which several parameters were analyzed, including coagulation factors. Materials and methods: The test included 120 rats, of both sexes, divided into six groups (main group, recovery group and control group) at which the human dose, 10X human dose and 1 control adjuvant were tested. The vaccine was administered intranasally, 4 times every two weeks. The final day was after the last administration to the main group and another 30 days from the last administration to the recovery group. On day 0 and the final day, blood was collected for hematological, biochemical, immunological examinations and coagulation tests (Fibrinogen, Prothrombin Time-PT, Activated Partial Thromboplastin Time-aPTT and Thrombin Time-TT). Results: Fibrinogen, in the case of all groups, increased on the final day, except for females from the recovery groups where this parameter decreased by 25%. PT, aPTT and TT, regardless of group or sex, had low values ​​compared to the initial time of the study. On day 0, the values ​​of the coagulation factors were homogeneous, the fibrinogen being between 155-347mg / dL, PT 25.5-57.8 sec, aPTT 61.9-120 sec and TT values ​​of 53-60 sec. On the final day, the group analysis also showed unit values. Fibrinogen increased between 90-116%, PT decreased by 48-71%, aPTT decreased by 59-80%, and TT had values ​​lower by 10-14% compared to the initial day. Conclusions: Increased fibrinogen associated with decreased PT and aPTT is common in human clinical pathology. Fibrinogen, PT, aPTT and TT are the standard parameters of blood clotting assessed in toxicity tests. The results obtained in the study represent a preliminary phase which, corroborated with the results of the other tests, supports the conclusion that the candidate vaccine does not have toxicological potential, the coagulation factors not being influenced after its repeated administration. Keywords: SARS-CoV-2, coagulation factors, rat, vaccine"