Dataset Information

Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats.

ABSTRACT:

Purpose

Our objective was to evaluate the influence of pretreatment with tocilizumab (TCZ) in bone healing after tooth extraction in rats.

Methods

Wistar male rats were equally divided into sham (ie, nonoperated), saline (both treated with 0.1 ml/kg saline), and six TCZ groups treated with 1, 2, 4, 8, 16, and 32 mg/kg TCZ (TCZ1 to TCZ32, respectively). Twenty-four hours after administration of vehicle or TCZ, exodontia of the first lower left molar was performed, and the animals were euthanized three days later for hematological analysis and organ (liver, spleen, and kidney mass indexes, and histological evaluation), gingiva (myeloperoxidase [MPO] assay), and mandible (radiographic, histomorphometric analysis, and IL-6 immunostaining) evaluation. Analysis of variance/Bonferroni test (statistical significance, P < .05) was performed using GraphPad Prism version 5.0 (GraphPad Inc, San Diego, CA, USA).

Results

There was no difference in radiographic results; however, leukopenia (P = .039) and neutropenia (P < .001) were statistically significant in the TCZ16 and TCZ32 groups. Weight loss (P < .001) and reduced liver index (P = .001) were significantly dose-dependent; however, no histological alterations were observed in the other organs. Osteoclast counts were reduced in groups TCZ4 to TCZ32 (P < .001), and IL-6 immunostaining increased in the TCZ8 to TCZ32 groups (P < .001). Alveolar infection rates increased in groups TCZ4 to TCZ32 (P < .001), and MPO had a biphasic response, exhibiting a reduction in groups TCZ2 and TCZ4, and an increase in group TCZ32 (P = .004).

Conclusion

TCZ-induced immunosuppression led to a reduction in osteoclast function, an increase in alveolar infection, and compensatory neutrophil infiltration.

SUBMITTER: Imaculada de Queiroz Rodrigues M

PROVIDER: S-EPMC7428756 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats.

Imaculada de Queiroz Rodrigues Maria M Ohana de Lima Martins Joyce J Silva Paulo Goberlânio de Barros PGB Carlos Ferreira Júnior Antônio Ernando AE Quezado Lima Verde Maria Elisa ME Sousa Fabrício Bitú FB Lima Mota Mário Rogério MR Negreiros Nunes Alves Ana Paula AP

Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 20200815 12

<h4>Purpose</h4>Our objective was to evaluate the influence of pretreatment with tocilizumab (TCZ) in bone healing after tooth extraction in rats.<h4>Methods</h4>Wistar male rats were equally divided into sham (ie, nonoperated), saline (both treated with 0.1 ml/kg saline), and six TCZ groups treated with 1, 2, 4, 8, 16, and 32 mg/kg TCZ (TCZ1 to TCZ32, respectively). Twenty-four hours after administration of vehicle or TCZ, exodontia of the first lower left molar was performed, and the animals w ...[more]

PMID: 32919953

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Project description:Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic diseases, but the diagnostic impact in CMT is yet to be fully reported. We present the diagnostic results from a single specialist inherited neuropathy centre, including the impact of WGS diagnostic testing. Patients were assessed at our specialist inherited neuropathy centre from 2009 to 2023. Genetic testing was performed using single gene testing, next-generation sequencing targeted panels, research whole exome sequencing and WGS and, latterly, WGS through the UK National Health Service. Variants were assessed using the American College of Medical Genetics and Genomics and Association for Clinical Genomic Science criteria. Excluding patients with hereditary ATTR amyloidosis, 1515 patients with a clinical diagnosis of CMT and related disorders were recruited. In summary, 621 patients had CMT1 (41.0%), 294 CMT2 (19.4%), 205 intermediate CMT (CMTi, 13.5%), 139 hereditary motor neuropathy (HMN, 9.2%), 93 hereditary sensory neuropathy (HSN, 6.1%), 38 sensory ataxic neuropathy (2.5%), 72 hereditary neuropathy with liability to pressure palsies (HNPP, 4.8%) and 53 'complex' neuropathy (3.5%). Overall, a genetic diagnosis was reached in 76.9% (1165/1515). A diagnosis was most likely in CMT1 (96.8%, 601/621), followed by CMTi (81.0%, 166/205) and then HSN (69.9%, 65/93). Diagnostic rates remained less than 50% in CMT2, HMN and complex neuropathies. The most common genetic diagnosis was PMP22 duplication (CMT1A; 505/1165, 43.3%), then GJB1 (CMTX1; 151/1165, 13.0%), PMP22 deletion (HNPP; 72/1165, 6.2%) and MFN2 (CMT2A; 46/1165, 3.9%). We recruited 233 cases to the UK 100 000 Genomes Project (100KGP), of which 74 (31.8%) achieved a diagnosis; 28 had been otherwise diagnosed since recruitment, leaving a true diagnostic rate of WGS through the 100KGP of 19.7% (46/233). However, almost half of the solved cases (35/74) received a negative report from the study, and the diagnosis was made through our research access to the WGS data. The overall diagnostic uplift of WGS for the entire cohort was 3.5%. Our diagnostic rate is the highest reported from a single centre and has benefitted from the use of WGS, particularly access to the raw data. However, almost one-quarter of all cases remain unsolved, and a new reference genome and novel technologies will be important to narrow the 'diagnostic gap'.

Dataset Information

Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats.

Purpose

Methods

Results

Conclusion

Publications

Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats.

Similar Datasets

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