Population structure and genomic footprints of selection in five major Iranian horse breeds.

The genetic structure and characteristics of Iranian native breeds are yet to be comprehensibly investigated and studied. Therefore, we employed genomic information of 364 Iranian native horses representing the Asil (n = 109), Caspian (n = 40), Dareshuri (n = 44), Kurdish (n = 95), and Turkoman (n = 76) breeds to reveal the genetic structure and characteristics. For these and 19 other horse breeds, principal component analysis, Bayesian model-based, Neighbor-Net, and bootstrap-based TreeMix approaches were applied to investigate and compare their genetic structure. Additionally, three haplotype-based methods including haplotype homozygosity pooled, integrated haplotype score, and number of segregating sites by length were applied to trace genomic footprints of selection of Asil, Caspian, Dareshuri, Kurdish, and Turkoman groups. Then, the Mahalanobis distance based on the negative-log10 rank-based P-values was estimated based on the haplotype homozygosity pooled, integrated haplotype score, and number of segregating sites by length values. Asil, Caspian, Dareshuri, Kurdish, and Turkoman can be categorized into five different genetic clusters. Based on the top 1% of Mahalanobis distance based on the negative-log10 rank-based P-values of SNPs, we identified 24 SNPs formerly reported to be associated with different traits and >100 genes undergoing selection pressures in Asil, Caspian, Dareshuri, Kurdish, and Turkoman. The detected QTL undergoing selection pressures were associated with withers height, equine metabolic syndrome, overall body size, insect bite hypersensitivity, guttural pouch tympany, white markings, Rhodococcus equi infection, jumping test score, alternate gaits, and body weight traits. Our findings will aid to have a better perspective of the genetic characteristics and population structure of Asil, Caspian, Dareshuri, Kurdish, and Turkoman horses as Iranian native horse breeds.

Effect of teriparatide on the healing of mandibular condylar osteochondral defects: a preclinical study.

This study was performed to evaluate the effect of teriparatide therapy on the healing of osteochondral defects of the mandibular condylar. Ninety-six rats underwent surgery to create a defect in the condylar head on one side of the mandible, and were divided into two groups. One group received subcutaneous injection of 2 µg/kg/day teriparatide, and the other group received normal saline until sacrifice. On postoperative days 20, 40, and 60, 16 animals from each group were sacrificed, and bone and cartilage healing was histologically evaluated and semiquantitatively scored (1-5). The mean difference in healing score of the cartilaginous and subchondral parts of the defect between the teriparatide and control groups at days 20, 40 and 60 were 0.438 and 0.438, 0.813 and 0.750, and 1.125 and 0.813, respectively. The healing scores of the osteochondral defects in the teriparatide group were significantly (p< 0.05) higher than that in the control group at days 40 and 60. This study has shown beneficial effects of teriparatide on the healing of condylar osteochondral defects in rats. Clinical trials are required to extrapolate these findings to humans.

Detection of Common Copy Number of Variants Underlying Selection Pressure in Middle Eastern Horse Breeds Using Whole-Genome Sequence Data.

Dareshouri, Arabian, and Akhal-Teke are 3 Middle Eastern horse breeds that have been selected for endurance and adaptation to harsh climates. Deciphering the genetic characteristics of these horses by tracing selection footprints and copy number of variations will be helpful in improving our understanding of equine breeds' development and adaptation. For this purpose, we sequenced the whole genome of 4 Dareshouri horses using Illumina Hiseq panels and compared them with publicly available whole-genome sequences of Arabian (n = 3) and Akhal-Teke (n = 3) horses. Three tests of FLK, hapFLK, and pooled heterozygosity were applied using a sliding window (window size = 100 kb, step size = 50 kb) approach to detect putative selection signals. Copy number variation analysis was applied to investigate copy number of variants (CNVs), and the results were used to suggest selection signatures involving CNVs. Whole-genome sequencing demonstrated 8 837 950 single-nucleotide polymorphisms (SNPs) in autosomal chromosomes. We suggested 58 genes and 3 quantitative trait loci, including some related to horse gait, insect bite hypersensitivity, and withers height, based on selective signals detected by adjusted P-value of Mahalanobis distance based on the rank-based P-values (Md-rank-P) method. We proposed 12 genomic regions under selection pressure involving CNVs that were previously reported to be associated with metabolism energy (SLC5A8), champagne dilution in horses (SLC36A1), and synthesis of polyunsaturated fatty acids (FAT2). Only 10 Middle Eastern horses were tested in this study; therefore, the conclusions are speculative. Our findings are useful to better understanding the evolution and adaptation of Middle Eastern horse breeds.

Differences between health technology assessment topics in high- and middle-income countries: a scoping review.

BACKGROUND: The Health Technology Assessment (HTA) has encountered different issues and challenges over the last two decades. The main purpose of this research is to review the issues and challenges in high- and middle-income countries through reviewing studies related to the HTA. METHODS: The HTA area literature of different countries was collected from 2009 to 2020 and analyzed using scoping review, based on Scopus and WoS databases. RESULTS: Given the fact that the HTA is practically done in high- and middle-income countries, the results of reviewing the studies and articles of countries reveal that high-income countries seek to increase the participation of stakeholders and enhance the transparency of processes, policy-making, and regulation of the HTA, as well as the systematization of various participant institutions in this area. Middle-income countries, on the other hand, are mostly involved in raising awareness, training and skill development of HTA-related staff, institutionalizing the concept of HTA, and allocating appropriate resources for effective and safe decision-making in their health system. CONCLUSION: The problem of incoordination between stakeholders (participant institutions) in the HTA, and thereby, problems in decision-making were found in many of the studied reports and articles. Thus, one of the useful efforts to be made by different countries to maintain the integrity of this system would be the process of involving all members of this system and the formation of a healthy ecosystem in the HTA.

Manufacturing and Application of 3D Printed Photo Fenton Reactors for Wastewater Treatment.

Additive manufacturing (AM) or 3D printing offers a new paradigm for designing and developing chemical reactors, in particular, prototypes. The use of 3D printers has been increasing, their performance has been improving, and their price has been reducing. While the general trend is clear, particular applications need to be assessed for their practicality. This study develops and follows a systematic approach to the prototyping of Advanced Oxidation Processes (AOP) reactors. Specifically, this work evaluates and discusses different printable materials in terms of mechanical and chemical resistance to photo-Fenton reactants. Metallic and ceramic materials are shown to be impracticable due to their high printing cost. Polymeric and composite materials are sieved according to criteria such as biodegradability, chemical, thermal, and mechanical resistance. Finally, 3D-printed prototypes are produced and tested in terms of leakage and resistance to the photo-Fenton reacting environment. Polylactic acid (PLA) and wood-PLA composite (Timberfill®) were selected, and lab-scale raceway pond reactors (RPR) were printed accordingly. They were next exposed to H2O2/Fe(II) solutions at pH = 3 ± 0.2 and UV radiation. After 48 h reaction tests, results revealed that the Timberfill® reactor produced higher Total Organic Carbon (TOC) concentrations (9.6 mg·L-1) than that obtained for the PLA reactor (5.5 mg·L-1) and Pyrex® reactor (5.2 mg·L-1), which suggests the interference of Timberfill® with the reaction. The work also considers and discusses further chemical and mechanical criteria that also favor PLA for 3D-printing Fenton and photo-Fenton reactors. Finally, the work also provides a detailed explanation of the printing parameters used and guidelines for preparing prototypes.

The role of Rho-associated kinase inhibitor, Y-27632 on primary culture of ovine spermatogonial stem cells.

The access to sufficient numbers of spermatogonial stem cells (SSCs) is a prerequisite for the study of their regulation and further biomanipulation. Rho kinase (ROCK) belongs to a family of serine/threonine kinases and involves in a wide range of fundamental cellular functions. The aim of the present study was to study the effect of ROCK inhibitor, Y-27632 (0.1-40 µM), during the primary culture of ovine SSCs. SSCs were collected from 3-5-month-old's lamb testes. The viability of SSCs, the apoptosis assay of SSCs, the intracellular reactive oxygen species (ROS) analysis, and the SSCs markers and apoptosis-related gene expressions were detected by MTT reduction assay, Annexin V-FITC/ Propidium Iodide (PI) dual staining, flow cytometry and real-time-PCR studies, respectively. Morphological analyses indicated that the 5-10 µM Y-27632 had an optimal effect on the number of presumptive SSCs colonies and the area covered by them after a 10 days culture. The cell viability, apoptosis and necrosis of SSCs after 10 days' culture were not affected in comparison with the control group, and the 20 µM of Y-27632 resulted in significantly decreased cell viability (P<0.05) and an increased necrosis of cells. On day 10 after culture, the expression of P53 was decreased with an increase from 0 to 10 µM in the Y-27632 dose. In the 20 µM Y-27632 group, the expressions of P53 and Bax were higher and the Bcl-2 was lower than other groups and these values were significantly different from 5 and 10 µM Y-27632 groups (P<0.05). The level of intracellular ROS was decreased with an increase in the Y-27632 dose from 5 to 20 µM in comparison with the control group. In conclusion, the present study demonstrated that Y-27632 at a concentration of 5-10 µM provided optimal culture conditions for the primary culture of ovine SSCs.

Anatomical characteristics of mandibular bone in skeletal class I, II and III patients by using cone beam computed tomography images in an iranian population / Características anatômicas do osso mandibular em pacientes Classe I, II e III esquelética usando imagens de Tomografia Computadorizada de Feixe Cônico: em uma População Iraniana

Objetive: This study aimed to compare the anatomical characteristics of the mandible in patients with skeletal class I, II and class III disorders using cone beam computed tomography (CBCT). Material and Methods: CBCT scans of patients between 17 to 40 years taken with NewTom 3G CBCT system with 12-inch field of view (FOV) were selected from the archive. Lateral cephalograms were obtained from CBCT scans of patients, and type of skeletal malocclusion was determined (Class I, II or III). All CBCT scans were evaluated in the sagittal, coronal and axial planes using the N.N.T viewer software. Results: The ramus height and distance from the mandibular foramen to the sigmoid notch in class II patients were significantly different from those in skeletal class I (P < 0.005). Distance from the mandibular canal to the anterior border of ramus in class III individuals was significantly different from that in skeletal class I individuals (P < .005). Conclusion: Length of the body of mandible in skeletal class I was significantly different from that in skeletal class II and III patients. Also, ramus height in skeletal class I was significantly different from that in skeletal class II patients. CBCT had high efficacy for accurate identification of anatomical landmarks. (AU)

Objetivo: Este estudo teve como objetivo comparar as características anatômicas da mandíbula em pacientes com desordem esquelética Classe I, II e III usando imagens de tomografia computadorizada de feixe cônico (TCFC). Material e Métodos: Foram selecionadas de arquivo, imagens de TCFC (Sistema NewTon 3G) com FOV (campo de visão) 12 polegadas e incluindo pacientes entre 17 a 40 anos. Cefalometrias laterais foram obtidas a partir das imagens de TCFC e o tipo de maloclusão esquelética foi determinada (Classe I, II ou III). Todas as imagens de TCFC foram avaliadas nos planos sagital, coronal e axial usando o software de visualização N.N.T. Resultados: A altura do ramo e distância do forame mandibular para a incisura da mandíbula em pacientes Classe II foi significativamente diferente daqueles Classe I esquelética (p< 0.005). A distância do canal mandibular até a borda anterior do ramo em indivíduos Classe III foi significativamente diferente daqueles indivíduos Classe I esquelética (p<0.005). Conclusão: O comprimento do corpo da mandíbula na Classe I esquelética foi diferente significativamente daqueles pacientes em Classe II e III esquelética. Além disso, a altura do ramo na Classe I esquelética foi significativamente diferente daqueles pacientes Classe II esquelética. A TCFC apresentou alta eficácia para a identificação precisa de marcos anatômicos. (AU)

Wiz: A Web-Based Tool for Interactive Visualization of Big Data.

In an age of information, visualizing and discerning meaning from data is as important as its collection. Interactive data visualization addresses both fronts by allowing researchers to explore data beyond what static images can offer. Here, we present Wiz, a web-based application for handling and visualizing large amounts of data. Wiz does not require programming or downloadable software for its use and allows scientists and non-scientists to unravel the complexity of data by splitting their relationships through 5D visual analytics, performing multivariate data analysis, such as principal component and linear discriminant analyses, all in vivid, publication-ready figures. With the explosion of high-throughput practices for materials discovery, information streaming capabilities, and the emphasis on industrial digitalization and artificial intelligence, we expect Wiz to serve as an invaluable tool to have a broad impact in our world of big data.

Spermatogonial stem cell survival in ram lambs following busulfan treatment.

To clarify the effect of busulfan on the depletion of spermatogonial stem cells (SSCs) from shal rams testis, in the first experiment, lambs were treated by intraperitoneal injection with 4 mg/kg busulfan. In the second experiment, different concentrations of busulfan (1, 2 and 4 mg/kg) were injected directly into both sides of the left testis. The testes of 8 lambs were collected by standard castration procedure for histological analysis five weeks after the treatments and the left testis of remaining lambs were collected after eight weeks and a two-time enzymatic digestion process was used to isolate SSCs. The results showed that all rams that had received intraperitoneal injections of busulfan died. But by testicular injecting of same dose of the drug, 40% of the animals died. The testicular injection of rams with 1, 2 and 4 mg/kg of busulfan resulted in a dose dependent decrease in testis size and also spermatocytes population after 5 weeks of treatments. From the results of colony formation 8 weeks after treatment with busulfan, it can be concluded that only in 1 and 2 mg/kg of busulfan, recovery of endogenous germ cells was performed. In conclusion, the results demonstrated that intra-testicular injections of busulfan (2 mg/kg) reduced spermatocytes population in ram testis within 5 weeks of treatments, and this effect was reversible within 8 weeks of injection. However, it was not recommended to inject 4 mg/kg busulfan into the peritoneal cavity or testis of lambs based on its side effects.

Histological assessment of the effects of teriparatide therapy on mandibular fracture healing: A preclinical study.

OBJECTIVE: This study was performed to evaluate the effects of teriparatide therapy on mandibular fracture healing in a rat model. SUBJECTS AND METHODS: A unilateral mandibular fracture, 5 mm posterior to the last molar tooth, was surgically created in 120 rats. Half of the animals received a daily subcutaneous injection of 2 µg/kg teriparatide while the control rats received normal saline, starting from the day of surgery until sacrifice. Twenty rats from each group were sacrificed on postoperative days 10, 20, and 30. The healing process was evaluated histologically and scored using a grading system (ranging from 1 to 10). RESULTS: On day 10 the fracture gaps of the control and teriparatide groups were mainly filled with fibrous tissue and new trabecular bone, respectively. On day 20 a large amount of new trabecular bone and some areas of fibrocartilaginous tissue were seen in the fracture gaps of the control rats. In the teriparatide group the fracture area was entirely filled with trabecular bone, which in some areas had been replaced by mature bone. On day 30 the fracture gaps of the control group were entirely bridged by new trabecular bone, while in the teriparatide group they was predominantly filled with mature bone. At all three time-points the mean healing scores for the teriparatide group (6.20 ± 0.70, 8.50 ± 0.69, and 9.85 ± 0.37, respectively) were significantly higher (p < 0.001) than for the control group (4.90 ± 0.55, 7.15 ± 0.59, and 8.90 ± 0.64, respectively). CONCLUSION: Based on the results of this study, teriparatide should be tested in humans in order to establish whether comparable results can be achieved.

Histological evaluation of the healing process of autografted mandibular bone defects in rats under treatment with zoledronate.

OBJECTIVE: This study aims to evaluate the healing process of autografted mandibular bone defects in rats treated with zoledronate (ZOL). SUBJECTS AND METHODS: A total of 180 Wistar rats were divided into four groups: group L received intravenous infusion of two doses of 0.06 mg/kg ZOL, nine weeks apart; group H received 0.06 mg/kg ZOL, while groups C and NC received normal saline at three-week intervals for nine weeks. Three weeks following the last infusion, a unilateral mandibular bone defect (5 mm) was created. Except in the NC group, all defects were repaired with autologous iliac bone graft. Fifteen animals from each group were sacrificed on postoperative Day 20, Day 40, and Day 60. Graft healing was scored using a histological grading system (ranging from 1 to 6). RESULTS: Histological evaluations performed on postoperative Day 60 showed that the mandibular defects were mainly repaired with fibrous tissue in the NC and H groups (93.00% ± 7.51% and 82.67% ± 13.08%, respectively) and with bone in the C and L groups (75.33% ± 14.20% and 92.67% ± 8.84%, respectively). The percentage of fibrous tissue and bone as well as the healing score of the NC and H groups were significantly different (P = 0.001) from those of the C and L groups. However, these were not different between neither the NC and H groups nor the C and L groups. CONCLUSION: Based on the results of the present study the hypothesis can be established that there also might be a dose-dependent effect of ZOL on the healing of bone grafts in humans. This hypothesis has to be verified or rejected in clinical trials.

Evaluation of the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw.

OBJECTIVE: The aim of this study was to evaluate the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: To induce MRONJ, a total of 120 rats received intravenous zoledronate 0.06 mg/kg once a week for 6 weeks and their right mandibular first molar was extracted. Eighty of 94 rats with MRONJ were randomly selected and underwent unilateral mandibular osteotomy to replicate a fracture. After surgery, the rats were randomly assigned to T (teriparatide-treated) and C (control) groups. Group T (n = 40) received subcutaneous injection of 2 µg/kg/day teriparatide and group C (n = 40) received the same volume of normal saline until sacrifice. Four and 8 weeks after surgery, 20 rats in each group were sacrificed. Fracture healing was scored using a histological grading system (1 to 10). RESULTS: In group C, at 4 weeks and 8 weeks post-fracture, fibrous and cartilaginous tissues and scant bone formation at the fracture site and lacunae without osteocyte in adjacent mandibular bone were seen. In group T, substantial amounts of new trabecular bone rimmed by osteoblasts and some areas of remodeled mature bone were seen. After 8 weeks, extensive replacement of trabecular bone with mature bone occurred. Except between C4 and C8 groups, the healing score was significantly different between all subgroups. CONCLUSION: Teriparatide therapy successfully improved mandibular fracture healing in rats with MRONJ. However, this study was limited by the use of an animal model whose anatomy, physiology, and drug metabolism might be different from humans. CLINICAL RELEVANCE: The present study showed that teriparatide therapy may be used adjunctive to surgery in the treatment of mandibular fractures in MRONJ patients.

Evaluation of teriparatide effect on healing of autografted mandibular defects in rats.

OBJECTIVE: To evaluate the effects of short-term teriparatide administration on healing of autologous bone graft in mandibular critical-size defects. SUBJECTS AND METHODS: A 5-mm mandibular bone defect was created and iliac bone graft was harvested in 135 rats. Rats were randomly divided into 3 groups of negative control (NC), control (C), and study (S). In groups S and C, iliac graft was placed in defect and 2 µg/kg/day teriparatide or saline, respectively, was administered for 20 days. In group NC, iliac graft was not transferred to the defect and saline was injected for 20 days. Twenty, 40, and 60 days after surgery, 15 rats in each group were euthanized and the healing process was histologically evaluated and scored using a grading system (1-6). RESULTS: In group NC, defects did not heal or were predominantly filled with fibrous tissue. At day 20, bone defects in both C and S groups contained a large area of graft particles, numerous collagen fibers and some areas of new trabeculae. At the day 40, defects in group S showed a larger bone graft area, more new bone formation, smaller connective tissue area, and a higher healing score compared to group C (P < 0.05). At day 60, most of the defect in group S was filled with graft particles and mature bone while in group C, new trabecular bone formation was still underway (P < 0.05). CONCLUSION: Teriparatide therapy improves healing of bone defects reconstructed with autograft by reducing bone graft resorption and enhancing new bone formation and maturation.

Does zoledronate therapy make mandibular bone susceptible to fracture? A radiographical and biomechanical study in rats.

INTRODUCTION: The aim of this study was to evaluate the effect of zoledronate therapy on susceptibility of mandibular bone to fracture in rats. METHODS: Fifty rats were randomly allocated to two groups of 25 animals. The rats in group Z received monthly intravenous infusion of 0.06 mg/kg zoledronate for 6 months. The rats in the group C were injected with an equal volume of saline in the same manner. A month after the last zoledronate/saline administration, all 50 rats were euthanized. Using a cone beam computed tomography, the cortical thickness of inferior border of mandible and the mandibular bone mineral density were calculated, and using a three-point bending test, the peak load failure and the ultimate stress of mandibular bone were determined. RESULTS: The mean mandibular inferior cortical bone thickness and the mean bone mineral density were significantly larger in zoledronate-treated rats (0.30 ±â€¯0.02 mm and 1045.00 ±â€¯185.79, respectively) compared to control rats (0.21 ±â€¯0.01 mm and 878.66 ±â€¯166.53, respectively). The peak load and the ultimate stress were lower in the zoledronate-treated hemimandibles (84.61 ±â€¯33.62 N and 1.76 ±â€¯0.72 MPa, respectively) compared to the control hemimandibles (98.36 ±â€¯16.5 9 N and 2.03 ±â€¯0.44 MPa, respectively). CONCLUSION: Zoledronate therapy reduced the mechanical strength of the mandibles, implying an increased risk of mandibular fracture in rats.

Effects of grape seed extract, quercetin and vitamin C on ovine oocyte maturation and subsequent embryonic development.

The present study aimed to evaluate the effects of grape seed extract (GSE) versus quercetin and vitamin C on in vitro oocyte maturation and embryo development in sheep. The free radical scavenging activity of different concentrations of each product was measured by 1, 1- diphenyl-2-picryl hydrazyl (DPPH). Oocytes were collected from ovaries of slaughtered ewes and matured in TCM-199 medium containing fetal calf serum, follicle stimulating hormone (FSH), estradiol-17 ß, sodium pyruvate, and gentamicin sulfate. The in vitro fertilization and culture were performed using Bracket and Oliphant's (BO) medium and modified Charles Rosenkrans medium with amino acids (mCR2aa), respectively. The results showed that the hydroalcoholic extract of grape seed had free radical scavenging activity. IC50 value for GSE, vitamin C, and quercetin was found to be 585 µg/mL, 53 µg/mL, and 43 µg/mL, respectively. The concentrations, which showed beneficial effects on oocyte maturation and early development based on the mean number of cleavage, morula and blastocyst rates, were 25-200 µg/mL, 5 or 15 µg/mL, and 800 µg/mL, respectively, for vitamin C, quercetin and GSE. However, there were no significant differences between different concentrations of GSE and control. Findings also highlight the great effect on blastocyst rate while adding GSE at 800 µg/mL. However, the best rate of blastocyst production was obtained in presence of quercetin. Findings suggested the need for further studies on special molecules derived from GSE.

Assessment of palatal rugae pattern for sex and ethnicity identification in an iranian population.

BACKGROUND: Palatal rugoscopy is a reliable method in the forensic personal identification and racial group specification. the aim of the present study is to use palatal rugae pattern in sex and ethnicity identification applications. MATERIALS AND METHODS: Four hundred individual dental casts from four different ethnic populations of Iran were randomly selected. The pattern of the palatal rugae (shape, length, and number) investigated and its reliability to classify sex and minor ethnicity for each individual cast was evaluated. (P < 0.05) considered significant. RESULTS: The most common rugae shapes were straight, followed by wavy and curved types. The least frequent shapes were converging and circular types. Palatal rugae patterns were unique to each person. However, they could not differentiate males and females and had low abilities to classify the racial subsets. CONCLUSION: The palatal rugae pattern was unique to each individual and palatal rugoscopy can be considered as a reliable forensic identification tool where utilizing other methods such as DNA profiling, fingerprint, and dental record comparison is impossible or difficult. In this study, palatal rugoscopy was not a reliable method to classify the sex of an individual and to differentiate between different racial subsets.

Effect of different doses and durations of teriparatide therapy on resolution of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats.

OBJECTIVE: To evaluate the effects of different doses and durations of teriparatide therapy on MRONJ resolution in rats. SUBJECTS AND METHODS: A total of 120 rats that had been affected with MRONJ (after six weekly zoledronate injections and tooth extraction) were randomly divided into eight subgroups: 2, 10, and 20 µg/kg/day teriparatide were administered to L4, M4, and H4 for 4 weeks, and to L8, M8, and H8 for 8 weeks, respectively. C4 and C8 received saline for 4 and 8 weeks, respectively. One week after the final injection, rats were sacrificed and assessed clinically (bone exposure/fistula) and histologically (number of osteocytes in extraction socket and empty lacunae in alveolar bone). RESULTS: MRONJ was clinically improved in 72.2%, 61.5%, and 40% of stage I, II, and III experimental rats, respectively. In the control rats, the results were 20.8% for stage I and no improvement for stages II and III. Aside from L4 and L8, the experimental subgroups had a significantly higher rate of clinical and histological improvement compared with their corresponding controls. There was a significantly higher number of osteocytes and lower number of empty lacunae in M4 and H4 compared with C4, in H4 compared with L4, in M8 and H8 compared with C8, and in H8 compared with L8. CONCLUSION: Teriparatide therapy improved clinical and histological features of MRONJ in a dose-dependent manner, but clinically relevant doses of teriparatide might not be sufficient for MRONJ resolution in rats. Extending the duration of teriparatide therapy from 4 to 8 weeks did not affect treatment outcomes.

Evaluation of mandibular fracture healing in rats under zoledronate therapy: A histologic study.

INTRODUCTION: To evaluate fracture healing in mandible of rats under zoledronate therapy. METHODS: A total of 135 Wistar rats were randomly allocated into 3 groups. Group L received two intravenous infusion of 0.06 mg/kg zoledronate 6 weeks apart. Group H received the same dose of zoledronate as group L once a week for 6 weeks and group C were treated with normal saline. Seven days after the last infusion, rats underwent unilateral mandibular osteotomy to replicate a fracture. Fifteen rats from each group were sacrificed 2, 4, and 6 weeks after surgery. Fracture calluses were examined and scored using a histological grading system (1 to 10). RESULTS: After 2 weeks, substantial woven bone and some lamellar bone were seen in control and L groups. In group H, healing was delayed and consisted of fibrous and cartilaginous tissue and some woven bone. After 4 weeks, most of woven bone in control group was replaced with lamellar bone but in group L, comparatively less bone remodeling occurred. In group H, healing process was nearly the same as that at 2 weeks. After 6 weeks, complete bone remodeling was seen in control group. In group L, bone remodeling was under way and in group H, histological findings were nearly the same as those at 2 and 4 weeks. Except for L and control groups at 2 weeks, healing score was significantly different between all corresponding groups. CONCLUSION: Zoledronate therapy delayed healing process of mandibular fracture in rats in a dose-dependent manner.

Short-term perioperative teriparatide therapy for the prevention of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats.

OBJECTIVE: Dentoalveolar procedures in patients receiving bisphosphonates and other antiresorptive agents are associated with an increased risk of medication-related osteonecrosis of the jaw (MRONJ). The aim of present study was to evaluate the effects of perioperative teriparatide (TPD) therapy in prevention of MRONJ. SUBJECTS AND METHODS: Two protocols of TPD therapy were studied. For protocol A, 25 TPD-treated (AT) and 25 control (AC) rats received 5 weekly injection of 0.06 mg/kg zoledronate. At the end of week 5, extraction of bilateral mandibular first molars was performed for all rats, and 4-week TPD (20 µg/kg/day) and saline therapy was started for AT and AC rats, respectively. For protocol B, 25 TPD-treated (BT) and 25 control (BC) rats received 5 weekly injection of 0.06 mg/kg zoledronate. One week later, 4-week TPD and saline therapy was started for BT and BC rats, respectively. Both groups underwent tooth extraction at the end of week 7 of the experiment. All rats were sacrificed 8 weeks after tooth extraction and assessed clinically for bone exposure/fistula, and histologically for density of osteocytes in newly formed bone and empty osteocyte lacunae in alveolar bone. RESULTS: Incidence of bone exposure/fistula and mean numbers of osteocytes and empty lacunae per 25 mm2 (at 400× magnification) were 20%, 15.36, and 2.63 in AT group; 78%, 5.78, and 6.81 in AC group; 14%, 16.94, and 2.08 in BT group; and 78%, 7.54, and 5.95 in BC group; respectively. The differences between AT and AC and between BT and BC were statistically significant (P < 0.001). However, no statistically significant difference between AT and BT and between AC and BC was found. CONCLUSION: Four weeks of TPD therapy, beginning at the same day or 2 weeks before tooth extraction, had a potential role in prevention of ONJ.