Positive Osteocalcin Expressions in Periodontium Regenerated by Nano Bioceramics after Orthodontic Tooth Movement

The research is to analyse the immunohistochemical reaction of orthodontic force on the periodontium reformed by nanobiphasic calcium phosphate ceramics (nBCP). Two third incisors were selected randomly and operated as experimental groups in 2 Beagle dogs. In the labial aspects of the third incisors, alveolar bone defects were surgically made and implanted with NBCP. The contralateral teeth in the same jaw did not receive any treatment as control. After 24 weeks, all the third incisors were moved labially. The dogs were euthanized 4 weeks later. The expression levels of osteocalcin were detected by immunohistochemical staining. Positive osteocalcin expressions in regenerated periodontium were observed and compared with the normal periodontium in the control groups. There were no significant differences within and between them. It means the periodontium regenerated by nBCP can bear orthodontic forces with a normal function. Based on these findings, we concluded that nBCP may offer a new bone graft choice for periodontic disease patients who have demands for orthodontic treatment.

Canine transmissible venereal tumour established in immunodeficient mice reprograms the gene expression profiles associated with a favourable tumour microenvironment to enable cancer malignancy

Background Canine transmissible venereal tumours (CTVTs) can cross the major histocompatibility complex barrier to spread among dogs. In addition to the transmissibility within canids, CTVTs are also known as a suitable model for investigating the tumour–host immunity interaction because dogs live with humans and experience the same environmental risk factors for tumourigenesis. Moreover, outbred dogs are more appropriate than inbred mice models for simulating the diversity of human cancer development. This study built a new model of CTVTs, known as MCTVTs, to further probe the shaping effects of immune stress on tumour development. For xenotransplantation, CTVTs were first injected and developed in immunodeficient mice (NOD.CB17-Prkdcscid/NcrCrl), defined as XCTVTs. The XCTVTs harvested from NOD/SCID mice were then inoculated and grown in beagles and named mouse xenotransplantation of CTVTs (MCTVTs). Results After the inoculation of CTVTs and MCTVTs into immune-competent beagle dogs separately, MCTVTs grew faster and metastasized more frequently than CTVTs did. Gene expression profiles in CTVTs and MCTVTs were analysed by cDNA microarray to reveal that MCTVTs expressed many tumour-promoting genes involved in chronic inflammation, chemotaxis, extracellular space modification, NF-kappa B pathways, and focal adhesion. Furthermore, several well-known tumour-associated biomarkers which could predict tumour progression were overexpressed in MCTVTs. Conclusions This study demonstrated that defective host immunity can result in gene instability and enable transcriptome reprogramming within tumour cells. Fast tumour growth in beagle dogs and overexpression of tumour-associated biomarkers were found in a CTVT strain previously established in immunodeficient mice. In addition, dysregulated interaction of chronic inflammation, chemotaxis, and extracellular space modification were revealed to imply the possibly exacerbating mechanisms in the microenvironments of these tumours. In summary, this study offers a potential method to facilitate tumour progression and provide a niche for discovering tumour-associated biomarkers in cancer research.

Improved accuracy of digital implant impressions with newly designed scan bodies: an in vivo evaluation in beagle dogs

Background The accuracy of digital impressions for fully edentulous cases is currently insufficient for routinely clinical application. To overcome the challenge, a modified scan body was introduced, which demonstrated satisfactory accuracy in vitro. The aim of this study was to evaluate the accuracy of digital impressions using the modified scan bodies with extensional structure versus scan bodies without extensional structure in mandible with two implants in beagle dogs. Methods The unilateral mandibular second premolar to second molar were extracted in four beagle dogs. Twelve weeks later, two implants were placed. Five repeated digital impressions were performed with an intraoral scanner on each dog using each of the two different scan bodies: Group I—scan body without extensional structure (SB); Group II—scan body with extensional structure (SBE). The scans were exported to Standard Tessellation Language (STL) files to serve as test data. The dogs were sacrificed and the dissected mandibles were digitalized with a lab scanner to provide reference data. Linear and angular deviations were calculated in an inspection software for accuracy assessment. Statistical analysis was performed with two-way ANOVA. The level of significance was set at α = 0.05. Results For trueness assessment, the mean of absolute linear/angular deviations were 119.53 μm/0.75 degrees in Group I and 68.89 μm/0.36 degrees in Group II. SBE was more accurate than SB regarding both linear (p = 0.008) and angular (p = 0.049) deviations. For precision assessment, the mean of absolute linear/angular deviations were 63.01 μm/0.47 degrees in Group I and 38.38 μm/0.24 degrees in Group II. No significant difference was found. Conclusions The application of SBE significantly improved the trueness of digital impressions in mandible with two implants compared to SB. No significant difference was found in terms of precision.

The Effect of Posaconazole and Isavuconazole on the Pharmacokinetics of Erdafitinib in Beagle Dogs by UPLC-MS/MS

Objective: A robust, quick, and reliable ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for the quantification of erdafitinib in beagle dog plasma was developed and validated to evaluate the changes of posaconazole and isavuconazole on the pharmacokinetics of erdafitinib in beagle dogs, respectively.Methods: This experiment adopted a three-period self-control experimental design. In the first period (group A), erdafitinib was orally administered to six beagle dogs at a dose of 4 mg/kg. In the second period (group B), the same six beagle dogs were orally given posaconazole at a dose of 7 mg/kg, and after 30 min, erdafitinib was orally given. In the third period (group C), isavuconazole at a dose of 7 mg/kg was given orally, and then, erdafitinib was orally given. At the different time points after erdafitinib was given in the three periods, the blood samples were collected. The concentration of erdafitinib was detected by the developed UPLC-MS/MS method. DAS 2.0 was used to calculate the pharmacokinetic parameters of erdafitinib.Results: Erdafitinib had a good linear relationship in the range of 1–500 ng/ml, and the lower limit of quantification was 1 ng/ml. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. After erdafitinib was combined with posaconazole, the Cmax and AUC0→t of erdafitinib increased by 27.19% and 47.62%, respectively, and the t1/2 was prolonged to 6.33 h. After erdafitinib was combined with isavuconazole, the Cmax and AUC0→t of erdafitinib increased by 23.13% and 54.46%, respectively, and the t1/2 was prolonged to 6.31 h.Conclusion: A robust and reliable UPLC-MS/MS method was fully optimized and developed to detect the plasma concentration of erdafitinib in beagle dogs. Posaconazole and isaconazole could inhibit the metabolism of erdafitinib in beagle dogs and increase the plasma exposure of erdafitinib.

Effect of Sijunzi Pills on Pharmacokinetics of Omeprazole in Beagle Dogs by HPLC-UV: A Herb-Drug Interaction Study

A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from −1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The Cmax of omeprazole in group B was 61.55% higher than that in group A, and the AUC(0−t) and AUC(0−∞) of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.