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Purpose: To evaluate a new cultivated coral graft (CCG) in an in vivo experimental guided bone regeneration (GBR) procedure. Materials and Methods: The calvarias of eight rabbits were surgically exposed, and circular defects 8 mm in diameter were prepared. One defect was filled with CCG particles (experimental group); the contralateral defect (control group) was spontaneously filled by blood clot. All defects were covered with a collagen membrane. Subjects were euthanized after 8 weeks. Results: Histologic observations of the defects showed similar bone growth patterns in both experimental and control osteotomies. In the experimental defects, no traces of coral particles were observed. Histometric analysis showed denser bone in the pristine zone (65%-66%) than in the peripheral zone for both the control (50%) and experimental defects (31%) (P = not significant). The new bone percentage was reduced from the peripheral zone toward the middle and the center of the defect (31%, 32%, and 27%, respectively) as the distance from the peripheral pristine bone borders increased. Conclusions: The existing data supports the complete degradation of CCG as a space-maintaining scaffold for GBR procedures. [ABSTRACT FROM AUTHOR]

Purpose: Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks). Materials and Methods: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers. Results: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CDIIb, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants. Conclusions: Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of sinus membrane stabilization (via suturing) and dental implant placement on the endo-sinus bone formation in lateral sinus elevations performed without grafting. Materials and Methods: Maxillary sinus elevation surgery using the lateral approach was performed bilaterally on 30 New Zealand white rabbits. The maxillary sinus areas were divided into control and test groups. In the control group, a titanium screw was placed after sinus membrane elevation; in the test group, the sinus membrane was sutured to the lateral walls, and a titanium screw was placed in the center of the alveolar crest. The subjects were sacrificed at 4 and 8 weeks. Then samples were collected, and a microcomputed tomography (micro-CT) analysis was performed. In addition, the volume of newly formed bone, percentage of osseointegration, sinus volume, residual bone height, and implant protrusion length were measured using micro-CT analysis. Results: The sinus volume, volume of newly formed bone, and percentage of osseointegration in the test group were significantly higher than in the control group at 4 weeks (P = .01, P = .04, P = .02, respectively). While the volume of newly formed bone was 17.1 ± 3.08 mm3 in the control group, it was 26.9 ± 14.26 mm3 in the test group at 4 weeks. The volume of newly formed bone significantly decreased from 26.9 ± 14.26 mm3 to 17 ± 3.66 mm3 at 8 weeks (P = .02). No significant difference in residual bone height was found at 4 and 8 weeks (P = .07). No significant difference in implant protrusion length was found between the control and test groups (P = .18). Protrusion length and new bone formation in the sinus showed a negative relationship (P = .01). Conclusions: Suturing the sinus membrane to the lateral sinus wall is an effective approach for increasing osseointegration, bone volume, and sinus volume in the short term. A slow-absorbing suture material can be used to maintain sinus and bone volumes in the long term. [ABSTRACT FROM AUTHOR]

PurposeThis study assessed the safety and efficacy of transepithelial crosslinking (CXL) using femtosecond (FS) laser-machined epithelial microchannels (MCs) followed by UVA CXL compared to FS laser (NLO CXL) in rabbits.MethodsThe epithelium of 36 rabbits was machined to create 2- by 25-µm MCs at 400 MCs/mm2. Eyes were treated with 1% riboflavin (Rf) solution for 30 minutes, rinsed, and then crosslinked using UVA or NLO CXL. Rabbits were monitored by epithelial staining, optical coherence tomography (OCT) imaging, and esthesiometry. After sacrifice at 2, 4, or 8 weeks, corneas were examined for collagen autofluorescence and immunohistochemistry.ResultsNLO CXL showed no epithelial damage compared to UVA CXL, which produced on average 23.89 ± 5.6 mm2 epithelial defects that healed by day 3. UVA CXL also produced loss of corneal sensitivity averaging 0.83 ± 0.24 cm force to elicit a blink response that persisted for 28 days and remained significantly lower than control or NLO CXL. OCT imaging detected the presence of a demarcation line only following UVA CXL but not NLO CXL.ConclusionsEven with improved transepithelial Rf penetration, UVA CXL resulted in severe epithelial damage, loss of corneal sensitivity, and delayed wound healing persisting for a month. When MCs were paired with NLO CXL, however, these issues were mostly negated. This suggests that MC NLO CXL can achieve a faster visual recovery without postoperative pain or risk of infection.Translational relevanceUVA CXL is a successful procedure, but there is a need for a transepithelial protocol. The combination of MCs and NLO CXL is able to keep the benefits of UVA CXL without causing epithelial damage.

Photo-sono therapy (PST) is an innovative anti-vascular approach based on cavitation-induced spallation. Currently, passive cavitation detection (PCD) is the prevalent technique for cavitation monitoring during treatment. However, the limitations of PCD are the lack of spatial information of bubbles and the difficulty of integration with the PST system. To address this, we proposed a new, to the best of our knowledge, cavitation mapping method that integrates Doppler optical coherence tomography (OCT) with PST to visualize bubble dynamics in real time. The feasibility of the proposed system has been confirmed through experiments on vascular-mimicking phantoms and in vivo rabbit ear vessels, and the results are compared to high-speed camera observations and PCD data. The findings demonstrate that Doppler OCT effectively maps cavitation in real time and holds promise for guiding PST treatments and other cavitation-related clinical applications.

Purpose: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. Materials and Methods: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. Results: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. Conclusions: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of combined therapy of teriparatide and raloxifene on the osseointegration of titanium dental implants in a rabbit model of osteoporotic bone. Materials and Methods: Sixty female rabbits were randomly divided into six groups. The sham ovariectomy group (control) consisted of animals that received no medication. Animals in the ovariectomy group (OVX) underwent ovariectomy and received no medication. The combined group consisted of ovariectomized animals that received combined teriparatide (10 mg/kg) for 12 weeks and raloxifene (10 mg/kg) for 12 weeks. The sequential group (SEQ) consisted of ovariectomized animals that received teriparatide (10 mg/kg) for the first 6 weeks and raloxifene therapy (10 mg/kg) for the following 6 weeks sequentially. The parathormone (PTH) and raloxifene (RAL) groups consisted of ovariectomized animals that received only teriparatide (10 mg/kg) for 12 weeks or raloxifene (10 mg/kg) for 12 weeks, respectively. Dental implants (Bilimplant) were placed in the proximal metaphysis of both tibias in all rabbits. Histomorphometric and microCT studies were performed on the specimens obtained from the right tibia bone. Removal torque (RTQ) and implant stability quotient (ISQ) tests were performed on the specimens obtained from the left tibia bone. The results were compared and evaluated statistically. Results: RTQ analysis revealed a statistically significant difference between the mean values of the combined group (93.01 ± 27.19 Ncm) and the OVX group (49.6 ± 12.5 Ncm) (P = .015). The highest mean T0 (implantation day) value was obtained in the control group (67.1 ± 3.4 Ncm), and the lowest mean value was obtained in the OVX group (61.4 ± 3.8 Ncm). The highest T1 mean (3 months after implantation) was obtained by the combined group (76.6 ± 3.8 Ncm), and the lowest mean was obtained by the OVX group (68.9 ± 6.2 Ncm). Histomorphometric analyses showed that the mean percentage of bone-to-implant contact (BIC%) of the combined group (51.2%) was significantly higher than that of the OVX group (28.6%) (P =.006). In the microCT examinations, it was found that the mean BIC% value of the combined group (41.1%) was significantly higher than that of the OVX group (24.1%) (P < .001). Conclusions: According to the results of the current study, combined therapy of teriparatide and raloxifene improves the BIC and osseointegration of titanium dental implants in osteoporotic bone compared with sequential or independent therapy with these agents. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of continuous perioperative clopidogrel treatment on the osseointegration of titanium implants. Materials and Methods: A total of 32 New Zealand rabbits were randomly divided between two groups: a clopidogrel group (n = 16) and a control group (n = 16). For 1 week prior to the surgical placement of a titanium implant in their medial femoral condyle, rabbits in the clopidogrel group received 3 mg/kg of clopidogrel daily, and the control group received only the vehicle. This treatment was continued for another 6 weeks postoperatively. At 6 weeks, the rabbits were euthanized and postmortem histologic and histomorphometric evaluation of the implants was performed. Results: The surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection, or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that bone-to-implant contact (BIC) was 48.77% for the clopidogrel group and 34.65% for the control group, with statistically significant difference between them (P < .001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52% vs 28.74%, respectively; P <.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, respectively; P < .001) in proximity to the implant surface than the control group, while the mean trabecular number had no difference between groups (1.56 vs 1.60, respectively; P = .961). Conclusions: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy. [ABSTRACT FROM AUTHOR]

Refractive errors remain a global health concern, as a large proportion of the world's population is myopic. Current ablative approaches are costly, not without risks, and not all patients are candidates for these procedures. Electromechanical reshaping (EMR) has been explored as a viable cost-effective modality to directly shape tissues, including cartilage. In this study, stromal collagen structure and fibril orientation was examined before and after EMR with second-harmonic generation microscopy (SHG), a nonlinear multiphoton imaging method that has previously been used to study native corneal collagen with high spatial resolution. EMR, using a milled metal contact lens and potentiostat, was performed on the corneas of five extracted rabbit globes. SHG was performed using a confocal microscopy system and all images underwent collagen fibril orientation analysis. The collagen SHG signal in controls is uniform and is similarly seen in samples treated with pulsed potential, while continuous EMR specimens have reduced, nonhomogeneous signal. Collagen fibril orientation in native tissue demonstrates a broad distribution with suggestion of another peak evolving, while with EMR treated eyes a bimodal characteristic becomes readily evident. Pulsed EMR may be a means to correct refractive errors, as when comparing its SHG signal to negative control, preservation of collagen structures with little to no damage is observed. From collagen fiber orientation analysis, it can be inferred that simple DC application alters the structure of collagen. Future studies will involve histological assessment of these layers and multi-modal imaging analysis of dosimetry.

Patulin, an emerging mycotoxin with high toxicity, poses great risks to public health. Considering the poor antibody production in patulin immunization, this study focuses on the four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics to reveal the immune response of patulin in rabbits. The rabbit immunization was performed with the complete developed antigens of patulin, followed by the identification of the immune serum. A total of 554 differential proteins, including 292 up-regulated proteins and 262 down-regulated proteins, were screened; the differential proteins were annotated; and functional enrichment analysis was performed. The differential proteins were associated with the pathways of metabolism, gene information processing, environmental information processing, cellular processes, and organismal systems. The functional enrichment analysis indicated that the immunization procedures mostly resulted in the regulation of biochemical metabolic and signal transduction pathways, including the biosynthesis of amino acid (glycine, serine, and threonine), ascorbate, and aldarate metabolism; fatty acid degradation; and antigen processing and presentation. The 14 key proteins with high connectivity included G1U9T1, B6V9S9, G1SCN8, G1TMS5, G1U9U0, A0A0G2JH20, G1SR03, A0A5F9DAT4, G1SSA2, G1SZ14, G1T670, P30947, P29694, and A0A5F9C804, which were obtained by the analysis of protein-protein interaction networks. This study could provide potential directions for protein interaction and antibody production for food hazards in animal immunization.

The New Zealand white rabbit (Oryctolagus cuniculus) is a frequently used surgical model. Pain management after surgery is a critical aspect of animal welfare. Recently, a long-acting buprenorphine formulation (Ethiqa XR; EXR) was approved for use in rats and mice but has not yet been investigated in rabbits. The current study aimed to determine whether a single subcutaneous dose of 0.15mg/kg of EXR could achieve and maintain therapeutic buprenorphine plasma concentrations (0.1ng/mL) for 72h in male and female rabbits. We also evaluated the safety profiles of EXR and the fentanyl patch (FP) by assessing fecal output after surgery, because opioids are known to decrease intestinal motility. Behavior and pain scores were compared for rabbits that received either EXR or the FP after undergoing an annulus puncture procedure to induce osteoarthritis. EXR at 0.15mg/kg SC provided a shorter time to onset and sustained analgesia for 72h in male and female rabbits, whereas the FP provided suboptimal analgesia after 48h. Both EXR and FP reduced fecal output after surgery. Output returned to baseline levels within 72h for the EXR group and remained slightly below baseline at 96h after surgery for the fentanyl group. Grimace pain scores revealed no significant difference between treatment groups. These results suggest that EXR is a safe and effective option for postoperative pain management in rabbits.

PURPOSE: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model. METHODS: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31). RESULTS: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P

ObjectiveWith the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model.MethodsAn animal study was designed using 21 healthy male New Zealand rabbits. Gallium-68-labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa (n = 6) or lateral tongue (n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non-nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection.ResultsBuccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1-5) were identified. In addition, an average of 16.9 ± 3.3 non-sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent-of-injected dose (%ID) compared with non-sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48-h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative.ConclusionFluorescent-labeled Tc-99 m-tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer.Level of evidenceN/A Laryngoscope, 134:1299-1307, 2024.

Patients with chronic inflammatory disorders such as psoriasis have an increased risk of cardiovascular disease and elevated levels of LL37, a cathelicidin host defense peptide that has both antimicrobial and proinflammatory properties. To explore whether LL37 could contribute to the risk of heart disease, we examined its effects on lipoprotein metabolism and show that LL37 enhanced LDL uptake in macrophages through the LDL receptor (LDLR), scavenger receptor class B member 1 (SR-B1), and CD36. This interaction led to increased cytosolic cholesterol in macrophages and changes in expression of lipid metabolism genes consistent with increased cholesterol uptake. Structure-function analysis and synchrotron small-angle x-ray scattering showed structural determinants of the LL37-LDL complex that underlie its ability to bind its receptors and promote uptake. This function of LDL uptake is unique to cathelicidins from humans and some primates and was not observed with cathelicidins from mice or rabbits. Notably, Apoe-/- mice expressing LL37 developed larger atheroma plaques than did control mice, and a positive correlation between plasma LL37 and oxidized phospholipid on apolipoprotein B (OxPL-apoB) levels was observed in individuals with cardiovascular disease. These findings provide evidence that LDL uptake can be increased via interaction with LL37 and may explain the increased risk of cardiovascular disease associated with chronic inflammatory disorders.

Osteoporosis is an increasingly prevalent disease. The development of an osteoporosis-like experimental animal model is of great importance for the study of peri-implant osteogenesis in osteoporosis. The present authors aimed to establish a rapid modeling method of osteoporotic rabbits for implant-bone analysis and validate whether the models can affect the implant osseointegration. The present study included 29 female New Zealand rabbits (age: 5 to 6 months). Two rabbits were lost during anesthetization. Of the remaining 27 rabbits, 18 received an ovariectomy, with 9 receiving dexamethasone injections for 8 weeks (OVX+D group) and 9 receiving equivalent-volume saline injections (OVX group). As a control group, the remaining 9 rabbits were sham-operated and received an equivalent volume of normal saline (SHAM group). Then, serum biochemical markers of bone metabolism were detected and densitometric measurements were performed. Implants were then placed in the tibias of each rabbit. Bone samples (including implants) were obtained after 4, 8, and 12 weeks of healing and were subjected to histologic and histomorphometric analyses. The results showed that the OVX+D group experienced a 32% reduction in bone mineral density (BMD) from baseline. The BMD of the OVX+D group was significantly lower than that of the SHAM and OVX groups. Moreover, alkaline phosphatase (ALP) blood concentrations of in the OVX+D group were increased significantly. The osteoporotic rabbits exhibited marked decreases in osseointegration, characterized by slowed bone formation and decreased bone-to-implant contact (BIC). The combination of an ovariectomy and dexamethasone injections could experimentally induce osteoporosis in rabbits in the short term, which can be used as an appropriate animal model to study the osseointegration of implants under osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: To use histomorphometric analysis to evaluate bone reconstruction in rabbit calvaria with autogenous bone, anorganic bovine bone, undecalcified human tooth bone (UdTB), and decalcified human tooth bone (dTB) grafts. Materials and Methods: Extracted human teeth were crushed, and tooth bone with and without decalcification was prepared. Bony defects were made in 10 rabbit calvaria and allocated to one of the following four groups: group 1, in which UdTB was grafted; group 2, in which dTB was grafted; group 3, in which anorganic bovine bone was grafted; group 4, in which autogenous bone was grafted. The rabbits were sacrificed at 2 or 8 weeks postoperatively, and histomorphometric comparison was performed. Results: Histologically, new bone formation was observed at the defect margin and around all graft materials. The dTB group revealed significantly greater new bone areas at 2 and 8 weeks compared to the UdTB group and the anorganic bovine bone group (P < .05). The dTB group revealed no significant difference in the new bone area at 2 weeks but revealed significantly less new bone area at 8 weeks compared to the autogenous bone group (P < .05). The dTB group also revealed significantly less graft material area compared to the anorganic bovine bone group at 8 weeks (P < .05). The autogenous bone group revealed significantly less graft material area and significantly greater bone marrow area compared to other groups at 8 weeks (P < .05). Conclusions: Grafting with dTB resulted in better bone regeneration than UdTB and anorganic bovine bone grafting at 8 weeks and addresses the potential disadvantages of autogenous bone grafting. [ABSTRACT FROM AUTHOR]

BackgroundHydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration.MethodsA total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally (n = 15), (ii) slow drip saline intratracheally (n = 15), (iii) fast drip saline intratracheally (n = 15), and (iv) slow drip cobinamide intratracheally (n = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy.ResultsThe mean (± standard deviation) weight for all animals (n = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups (P

ObjectiveNumerous pharmacological and cell-based treatments have shown promise in preventing vocal fold (VF) scarring when applied at the time of injury. A common clinical scenario, however, is the finding of mature scar impeding voicing. Many treatments are less effective in remodeling existing scar tissue. This objective of this study is to determine if a cell-based outer vocal fold replacement (COVR) effectively restores VF function when applied to existing scar.MethodsEighteen rabbits were allocated to three groups: unilateral COVR implant at the time of cordectomy (acute COVR); unilateral cordectomy followed by COVR implant 2 months later (chronic COVR); and unilateral cordectomy followed by sham implant surgery 2 months later (chronic scar). Larynges were harvested 2 months after implant or sham surgery.ResultsAll larynges in the COVR groups demonstrated human leukocyte antigen labeling on immunohistochemistry (IHC). COVR groups had increased hyaluronic acid content compared with normal. VF stiffness as measured by elastic moduli in acute COVR and chronic COVR were similar to their contralateral unoperated VF.ConclusionCOVR implantation in both acutely injured and chronically scarred VF demonstrate persistence of implanted cells, restored tissue biomechanics, and increased hyaluronic acid content.Level of evidenceNA Laryngoscope, 134:764-772, 2024.

Background: Intervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD. Methods: First, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model. Results: The in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05). Conclusion: Combining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice. [ABSTRACT FROM AUTHOR]

Cardiac action potential (AP) alternans have been linked to the development of arrhythmia. AP alternans may be driven by AP instabilities, Ca2+ transient (CaT) instabilities, or both. The mechanisms underlying CaT driven AP alternans is well-supported experimentally, but the ionic mechanism underlying alternans driven by AP instabilities remain incompletely understood. Here we used the Ca2+ buffer BAPTA to remove the CaT and generate a model of AP alternans driven primarily by AP instabilities. In isolated rabbit ventricle myocytes, AP alternans induced by rapid pacing were either critically damped and persisted over time, overdamped and ceased over seconds, or underdamped progressing to 2:1 capture. Control cells predominantly exhibited critically damped alternans. In contrast, removing CaT with BAPTA destabilized alternans formation in a concentration dependent manner. Importantly, alternans were easier to induce in CaT free cells as evidenced by a higher alternans threshold relative to control cells. While the L-type Ca2+ channel agonist Bay K 8644 had a minor effect on alternans formation in myocytes with conserved CaT, combining the agonist with BAPTA markedly promoted the formation of underdamped alternans and increased the alternans threshold more than four-fold as compared to controls. Our data support a mechanistic model in which AP alternans are a primary self-sustained event in which the CaT serves as a dampening cue that curbs alternans development, likely via a canonical negative feedback process involving Ca2+ induced inhibition of L-type Ca2+ current. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect. Methods: PRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein–protein interaction network analysis. Results: The results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein–protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect. Conclusion: PRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect. [ABSTRACT FROM AUTHOR]

Corneal transplantation is the primary treatment for irreversible corneal diseases, but due to limited donor availability, bioengineered corneal equivalents are being developed as a solution, with biocompatibility, structural integrity, and physical function considered key factors. Since conventional evaluation methods may not fully capture the complex properties of the cornea, there is a need for advanced imaging and assessment techniques. In this study, we proposed a deep learning-based automatic segmentation method for transplanted bioengineered corneal equivalents using optical coherence tomography to achieve a highly accurate evaluation of graft integrity and biocompatibility. Our method provides quantitative individual thickness values, detailed maps, and volume measurements of the bioengineered corneal equivalents, and has been validated through 14 days of monitoring. Based on the results, it is expected to have high clinical utility as a quantitative assessment method for human keratoplasties, including automatic opacity area segmentation and implanted graft part extraction, beyond animal studies. [ABSTRACT FROM AUTHOR]

Purpose: Dexamethasone eye implant has been used to treat macular edema and non-infectious uveitis. To date, its ocular pharmacokinetics are not fully characterized, and the development of generic preparations is in progress, as the patent of the original brand expires soon. Therefore, this work was designed to 1) determine the time course of vitreous dexamethasone concentrations following intravitreal implantation in rabbits and 2) explore the alternative use of NDF-SI01 from a pharmacokinetic point of view compared to Ozurdex®, which is currentlyused in the market. Methods: Ozurdex® and NDF-SI01 were implanted into the right and left eyes of the rabbit, respectively. A serial vitreous collection was performed to minimize the sacrifice of animals, and dexamethasone concentrations were measured by HP LC-MS/MS. Results: After implantation, dexamethasone concentration reaches the maximum concentration (3.1 μg/mL) in 19.5 days and decreases with a half-life of 40.3 h. AUC and clearance are 683.9 μg·h/mL and 1.29 mL/h, respectively. There is no significant difference in pharmacokinetic parameters between NDF-SI01 and Ozurdex®. The overall patterns of the cumulative release of both implants are similar. Conclusions: NDF-SI01 could alternate Ozurdex® in clinics based on the in vivo comparative pharmacokinetic study and in vitro dissolution test. [ABSTRACT FROM AUTHOR]

Objectives: There are no studies related to the use of PRF associated with cyanoacrylates in fresh post-extraction sockets. Thus, the aim of this study was to assess the effect of ethyl-cyanoacrylate combined with PRF in fresh sockets of rabbits subjected to anticoagulant therapy. Methods: Twelve adults rabbits were selected and premedicated with heparin 1 week before surgery to induce and simulate anticoagulant therapy. Upper and lower first premolars on the right side were extracted and then were divided into four groups of three animals each, with the groups distributed according to the type of intervention in the sockets (n = 6): (1) clot and suture (control); (2) PRF and suture; (3) clot and ethyl-cyanoacrylate; (4) PRF and ethyl-cyanoacrylate. At 12 weeks, the animals were sacrificed and the sockets were analyzed histologically and quantitatively. Total bone area, inflammation infiltrate, and adhesive remnants were assessed. Results: No remnants of adhesive were found in the samples. Groups 1 and 2 showed the highest bone area (G1 = 37.87% ± 17.86; G2 = 30.31 ± 9.36) with significant differences to those treated with ethyl-cyanoacrylate adhesive (G3 = 26.6% ± 11.82; G4 = 24.29% ± 6.25). Conclusions: The groups that used ethyl-cyanoacrylate as a closure method in sockets exhibited less bone area than the groups that used sutures. Both groups that used PRF as therapy did not show a significant improvement in bone healing at 12 weeks compared with the clot groups. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Upper respiratory infections are a frequent problem in pet rabbits and rodents, and Mycoplasma pulmonis is 1 of the most common causes of respiratory infections in pet rats. M pulmonis was detected in 1967 in laboratory rabbits via culture of the nares and oropharynx, but overall, Mycoplasma is not commonly identified in the upper airway of rabbits. The objective of this study was to compare the prevalence of Mycoplasma sp detection via next-generation DNA sequencing on nasal swabs obtained from healthy and unhealthy rabbits. METHODS: The of nasal swabs from both healthy and unhealthy rabbits submitted for next-generation DNA sequencing from January 2022 to February 2023 were reviewed. Data gathered included signalment, whether or not Mycoplasma sp was detected, and the cell count and relative predominance of Mycoplasma sp compared to other organisms. RESULTS: 91 rabbits met the inclusion criteria, of which 49 were healthy and 42 were unhealthy. Overall, 52 of 91 (57.1%) rabbits were positive and 39 of 91 (42.8%) were negative for Mycoplasma sp. Mycoplasma positivity was significantly (P < .001) more common in healthy rabbits (37/49 [75.5%]) compared to unhealthy rabbits (15/42 [35.7%]). CLINICAL RELEVANCE: The fact that Mycoplasma positivity was common in both groups of rabbits, and particularly common in rabbits without upper respiratory signs, suggests that Mycoplasma may be normal nasal flora in rabbits. Further research is needed to determine whether Mycoplasma could function as an opportunistic pathogen in rabbits. [ABSTRACT FROM AUTHOR]

Context.--: Recent publications have featured immunohistochemistry (IHC) as a sensitive tool for detecting Mycobacterium tuberculosis and nontuberculous mycobacteria, but performance is limited to cases suspected to have mycobacterial infection. Objective.--: To examine cross-reactivity of a polyclonal antimycobacterial antibody with various types of pathogens, tissues, and inflammatory patterns. Design.--: Surgical pathology files during a period of 6 years were searched, and 40 cases representing a variety of pathogens, tissue types, and inflammatory responses were retrieved. Cases were stained with a rabbit polyclonal antimycobacterial antibody (Biocare Medical, Pacheco, California). The cases and associated histochemical stains, culture, and molecular results were reviewed by 3 pathologists. Results.--: All 8 cases of mycobacterial infection previously diagnosed by other methods were positive for mycobacteria by IHC. In addition, multiple bacterial and fungal organisms and 1 case of Leishmania amastigotes were also immunoreactive with the mycobacterial IHC. Conclusions.--: Although highly sensitive for mycobacteria, the polyclonal antibody shows significant cross-reactivity with other organisms. This is a sensitive but nonspecific stain that can be used as an alternative confirmation method for mycobacteria, but attention should be paid to inflammatory reaction and organism morphology when IHC is positive to avoid misdiagnosis. [ABSTRACT FROM AUTHOR]

Objective: Airway replacement is a challenging surgical intervention and remains an unmet clinical need. Due to the risk of airway stenosis, anastomotic separation, poor vascularization, and necrosis, it is necessary to establish the gold-standard outcomes of tracheal replacement. In this study, we use a large animal autograft model to assess long-term outcomes following tracheal replacement. Methods: Four New Zealand White rabbits underwent tracheal autograft surgery and were observed for 6 months. Clinical and radiographic surveillance were recorded, and grafts were analyzed histologically and radiographically at endpoint. Results: All animals survived to the endpoint with minimal respiratory symptoms and normal growth rates. No complications were observed. Computed tomography scans of the post-surgical airway demonstrated graft patency at all time points. Histological sections showed no sign of stenosis or necrosis with preservation of the native structure of the trachea. Conclusion: We established benchmarks for airway replacement. Our findings suggest that a rabbit model of tracheal autograft with direct reimplantation is feasible and does not result in graft stenosis or airway collapse. [ABSTRACT FROM AUTHOR]

Objective: Anterior disc displacement (ADD) has been used to establish temporomandibular joint disorder (TMD) models. Based on whether preserve of the retrodiscal attachment, the modelling methodologies include ADD with dissecting the retrodiscal attachment (ADDwd) and ADD without dissecting the retrodiscal attachment (ADDwod). This article aims to determine which model better matches the micromechanical and microstructural progression of TMD. Methods: Through meticulous microscopic observations, the microstructure and micromechanical deformation of the TMJ discs in ADDwd and ADDwod rabbit models were compared at 2 and 20 weeks. Result: Scanning electron microscopy and transmission electron microscopy showed that collagen fibres became slenderized and straightened, collagen fibrils lost diameter and arrangement in the ADDwd group at 2 weeks. Meanwhile, nanoindentation and atomic electron microscopy showed that the micro‐ and nano‐ mechanical properties decreased dramatically. However, the ADDwod group exhibited no significant microstructure and micromechanical deformations at 2 weeks. Dissection of the retrodiscal attachment contribute in the acceleration of disease progression at the early stage, the devastating discal phenotype remained fundamentally the same within the two models at 20 weeks. Conclusion: ADDwod models, induced stable and persistent disc deformation, therefore, can better match the progression of TMD. While ADDwd models can be considered for experiments which aim to obtain advanced phenotype in a short time. [ABSTRACT FROM AUTHOR]

Background: Chondroitin and glucosamine sulphates (CGS) are considered structure‐modifying drugs and have been studied in the prevention, delay or reversal of structural morphological changes in joints caused by osteoarthritis. Objective: The aim of the present study was to investigate the action of CGS on the progression of chemically induced osteoarthritis in the temporomandibular joint (TMJ) of rabbits by evaluating the serum levels of tumour necrosis factor (TNF‐α) and collagen in the articular discs. Materials and Methods: A sample of 36 male rabbits was divided into three groups: control (CG), osteoarthritis (OG) and treatment (TG). The disease was induced by intra‐articular injection of sodium monoiodoacetate (10 mg/mL) in the OG and TG groups bilaterally. After 10 days, the TG animals received subcutaneous injection of chondroitin sulphates and glucosamine (7.5 mg/kg) and the OG and CG received saline solution (50 μL). Euthanasia times were subdivided into 40 and 100 days. Collagen quantification was performed by biochemical and histological analysis and for the quantification of serum levels of TNF‐α, an enzyme immunoassay was used. Results: The TG showed an increase in the collagen area of the articular disc when compared to the CG and the OG. The increase collagen concentration in the discs did not show a statistically significant difference between the groups. Post‐treatment TNF‐α levels were significantly lower in TG compared to OG. Conclusions: The results indicate that CGS treatment delayed the degeneration of the collagen in the TMJ articular disc and reduced serum TNF‐α levels, indicating a preventive effect on OA progression. [ABSTRACT FROM AUTHOR]

This experiment was designed to explore how different types of probiotics affect the growth, carcass traits, and seasonal variations in growing New Zealand White rabbits (NZW). Two parallel experiments using the same strain of NZW during winter and summer, each alone from 5 to 13 weeks of age. Each experiment uses a total of 125 unsexed rabbits. These rabbits are separated into 5 groups of 25 rabbits each. Each group has five replicates, with five rabbits in every replicate. In each experiment, 1st group acting as the control group did not receive any probiotics. The 2nd was given a dose of 1 ml of Bifidobacterium bifidum, the 3rd received a dose of 1 ml of Lactobacillus acidophilus, and the 4th was treated with a 1 ml blend of both Bifidobacterium bifidum and Lactobacillus acidophilus, and 5th group was treated with 1 ml of Saccharomyces cerevisiae. Results indicated that the Bifidobacterium bifidum group had the best live body weight (LBW) values and daily weight gain (DWG). Meanwhile, during summer, the Lactobacillus acidophilus group had the best feed conversion ratio (FCR) and performance index (PI) values. Also, growing rabbits fed Lactobacillus acidophilus and Bifidobacterium bifiduim had significantly increased carcass traits during the summer and winter seasons. Furthermore, seasonal changes indicated that the Bifidobacterium bifiduim group improved LBW, DWG, and PI during summer than winter. So, it could be concluded that using Bifidobacterium bifidum can enhance rabbit growth by improving feed utilization and carcass traits, making it an effective addition to hot weather diets. [ABSTRACT FROM AUTHOR]

The current study was designed to investigate the effect of dried orange pulp inclusion (OP diet), natural zeolite addition (Z diet), or both (OPZ diet) compared to control (CON diet) on digestibility, growth performance, nitrogen utilization, blood biochemical, antioxidative status, and cecum microbiota of growing rabbits. Seventy-two V-line male rabbits (6 weeks old) were divided into 4 balanced experimental groups. Results showed that administration of dried orange pulp or zeolite especially the OPZ diet significantly improved nutrient digestibility and nutritive values. Rabbits fed the experimental diets (OP, Z, or OPZ) recorded significantly higher values of average daily gain, N-retention, and N-balance compared with those fed the CON diet. Data on blood biochemical, showed non-significant differences in globulin concentrations, and significant decreases in levels of cholesterol, LDL (low-density lipoproteins), triglycerides, and MDA (malondialdehyde) as an antioxidant biomarker with OP, Z, or OPZ diets. Moreover, the incorporation of orange pulp or zeolite in diets significantly decreased the cecal count of E. coli, with no significant difference in total bacterial count among the experimental groups. It could be concluded that a combination between dried orange pulp and natural zeolite in the diet can enhance the growth performance, antioxidant and health status of rabbits. [ABSTRACT FROM AUTHOR]

We investigated the relationship between the degree of alveolarization and ultrasound-assessed lung aeration in a validated preterm rabbit model of experimental bronchopulmonary dysplasia (BPD). Lung ultrasound findings were heterogeneously abnormal and consisted of zones with interstitial, interstitial-alveolar or consolidated patterns. The median radial alveolar count was 10.1 [8.4–11.5], 7.8 [6.1–9] and 7.3 [1.8–10.1] in rabbits with interstitial, interstitial-alveolar or consolidated ultrasound pattern, respectively (overall p = 0.036). Alveolar count and lung ultrasound score were significantly correlated (ρ = − 0.044 (95%CI: − 1; − 0.143), p = 0.009; τ-b = − 0.362 (95%CI: − 0.6; − 0.1), p = 0.017). [ABSTRACT FROM AUTHOR]

Background: Studies have described various surgical maneuvers in rhinoplasty to limit thickening from excessive scarring in the supratip region. This study aimed to compare the effectiveness of three maneuvers—a simple suture, a U suture, and bolster dressing—used to avoid supratip deformity in a rabbit model. Methods: Thirty-two male New Zealand white rabbits were included. The animals were divided into four groups, and dissection was performed in the supra-perichondrial plane up to the supratip region through an open rhinoplasty incision. After dissection, the following approaches were applied to the supratip region: Group 1, simple approximation suture; Group 2, U suture; Group 3, bolster dressing; and Group 4 (control group), no suture. All animals were sacrificed after 12 weeks. Histological analysis was performed. Results: In Group 4, scar thickness was significantly greater than in the other groups (p < 0.05). Group 3 had greater scar thickness than Group 2 (p < 0.05). The ratio of scar thickness to skin thickness was higher in Group 4 compared with the other groups (p < 0.05). Finally, there was no difference in the ratio of scar thickness to skin thickness between Groups 1, 2, and 3 (p > 0.05). Conclusions: In this study, it was concluded that surgical methods using sutures in the supratip region reduced scar thickness in a rabbit model, and these surgical methods had similar levels of effectiveness. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Repair of the damaged meniscus is a scientific challenge owing to the poor self-healing potential of the white area of the meniscus. Tissue engineering provides a new method for the repair of meniscus injuries. In this study, we explored the superiority of 2% hyaluronic acid chitin hydrogel in temperature sensitivity, in vitro degradation, biocompatibility, cell adhesion, and other biological characteristics, and investigated the advantages of hyaluronic acid (HA) and Transforming Growth Factor β1 (TGF-β1) in promoting cell proliferation and a matrix formation phenotype. The hydrogel loaded with HA and TGF-β1 promoted cell proliferation. The HA + TGF-β1 mixed group showed the highest glycosaminoglycan (GAG) content and promoted cell migration. Hydroxypropyl chitin (HPCH), HA, and TGF-β1 were combined to form a composite hydrogel with a concentration of 2% after physical cross-linking, and this was injected into a rabbit model of a meniscus full-thickness tear. After 12 weeks of implantation, the TGF-β1 + HA/HPCH composite hydrogel was significantly better than HPCH, HA/HPCH, TGF-β1 + HPCH, and the control group in promoting meniscus repair. In addition, the new meniscus tissue of the TGF-β1 + HA/HPCH composite hydrogel had a tissue structure and biochemical content similar to that of the normal meniscus tissue. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Interpretation Clemastine has emerged as a promising therapy for the restoration of neurologic function in patients with multiple sclerosis (MS). However, clemastine and other agents with prodifferentiative effects on oligodendrocyte progenitor cells (OPCs) in rodent models have underperformed in clinical trials. We hypothesized that the preclinical studies showed more robust effects because of the abundance of OPCs in rodent models. To better examine the therapeutic potential of clemastine, we examined its effect on demyelinated white matter lesions in rabbits, which exhibit progenitor densities and limited remyelination more closely matching those found in tissues from patients with MS.We used lysolecithin to induce demyelination in white matter of New Zealand rabbits and then administered oral clemastine (10mg/kg/day) for various periods before assessing the OPC and oligodendrocyte (OL) populations in these lesions.Daily administration of clemastine for the full study period (56 days) increased oligodendrogenesis in white matter lesions. However, shorter durations of treatment failed to increase overall OL density despite enhancing OPC‐to‐OL differentiation. This effect was due to exhaustion of the OPC pool, as the differentiating progenitors were not replaced because of reduced OPC proliferation. Notably, delayed administration of clemastine led to an accumulation of activated OPCs expressing markers of senescence.Although capable of driving OL differentiation, clemastine treatment in rabbits hampered progenitor pool replenishment, induced senescence, and promoted conversion of microglia/macrophages to a proinflammatory phenotype. Whether these effects would also occur in humans or with other prodifferentiative therapies should be studied further, but our data suggest the need to carefully consider progenitor dynamics in the treatment of MS. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Simple Summary: Rabbit hemorrhagic disease virus 2 (RHDV2) was reported in the United States in 2018 and has since spread across most of the country where it has a potential for adverse impacts on ecosystems, economic losses, and pet rabbit health. Using an emergency use authorized vaccine, seroconversion and protection was demonstrated in 3- to 7-week-old specific pathogen free laboratory rabbits. The purpose of the current study was to examine this protocol in pet rabbits, which would be inclusive of varied breeds and ages. Importantly, no significant differences were observed in routine clinical pathology measures. Seroconversion was also observed but was variable, and lower levels of seroconversion were associated with increased age. In general, while variable outcomes to vaccination are expected, these preliminary data underlie the importance of examining the response of pet rabbits to help optimize new vaccine protocols. We propose this will complement traditional vaccine studies, aid in maintaining the health of pet rabbits, and help in the ultimate control of this highly infectious virus. A recombinant vaccine for rabbit hemorrhagic disease virus 2, a highly pathogenic virus, was granted emergency use authorization in the United States after the detection and spread of the virus starting in 2018. The goal of the current study was to assess pet rabbits (n = 29) through physical examination and routine clinical pathology testing using repeated assessments post-vaccination. In addition, seroconversion was also monitored after the initial vaccination and booster vaccination. Neither owners nor clinicians detected any physical abnormalities in relationship to the vaccine protocol. Hematological and clinical biochemistry testing showed some changes although median values were within species specific reference intervals. A significant increase in antibody levels was observed at day 21 (post-initial vaccination) and day 49 (post-booster vaccination) versus that present at baseline (p < 0.0001). However, variability in study rabbits was noted with some individuals showing low antibody levels as well as a lower overall response in older rabbits (r = −0.56, p = 0.006). A second cohort of rabbits was assessed at 11–12 months post-initial vaccination. In this second group, antibody levels were not significantly different from baseline levels (p = 0.21). Additional studies should be conducted to further define the variability in seroconversion and the term of protection in pet rabbits as the industry moves forward in the optimization of RHDV2 vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: Investigating strategies to mitigate weaning stress in rabbits holds considerable relevance for the rabbit breeding industry. Epigallocatechin gallate (EGCG), the predominant polyphenol in green tea, is recognized for its extensive health benefits. This study aimed to investigate the impact of dietary supplementation with EGCG on the antioxidant status, immune response, and intestinal microbiota in post-weaning rabbits. The results indicated that EGCG could effectively alleviate oxidative stress induced by weaning, as evidenced by enhanced antioxidant capacity, reduced peroxide generation, increased antioxidant enzymatic activity, improved intestinal morphology, decreased intestinal inflammation, and modulated intestinal microbiota flora. This information is essential for rabbit breeders seeking effective methods to mitigate post-weaning stress. This study was conducted to investigate the impact of EGCG on antioxidant stress, immune response, and intestinal microbiota flora in post-weaning rabbits. A total of 144 40 d Ira rabbits (equally divided by sex), were randomly allocated to six treatments. with five groups receiving doses of 200, 400, 600, 800, and 1000 mg/kg of EGCG, while one group served as a control without EGCG. Over 48 days, this study the assessed growth performance, antioxidant capacity, immune system, intestinal morphology, and cecal microbiota in the rabbits. The results showed that EGCG did not affect growth performance; however, significant linear and quadratic correlations were observed between the MDA, T-AOC, and GSH-Px activities in the liver and jejunum (p < 0.05). Quadratic effects were observed for the spleen and thymus indexes and serum IgG levels with increasing EGCG dosages (p < 0.05). Additionally, positive linear and quadratic effects were found on the ileal villus height and the villus height/crypt depth ratio. The relative abundances of Euryarchaeota, Patescibacteria, and Synergistota were significantly enriched in rabbits fed with high dosages (600–1000 mg/kg) of EGCG. Conclusively, the addition of large doses of EGCG (400–800 mg/kg) can effectively suppress oxidative stress and alleviate weaning stress, thereby contributing to the protection of post-weaning rabbits. [ABSTRACT FROM AUTHOR]

Simple Summary: The demand for animal-assisted services (AAS) has increased in the past decades. The participation of supporting animals in complementary therapy for humans is a developing area. While dogs and horses are the most widely utilized species in AAS, several unconventional species have already been involved, although there is a lack of information about the effects of the stress they may experience. During the interventions, animals may experience stress that can potentially violate aspects of animal welfare. This review seeks to identify criteria for selecting unconventional animal species, such as guinea pigs, rabbits, farm animals, alpacas, donkeys, reptiles, aquarium fishes, and dolphins, for AAS, considering factors such as temperament, trainability, human–animal bond potential, stress measurement, and stress mitigation strategies. Despite the growing interest in AAS, our literature review underscores the scarcity of research exploring their effects on unconventional animal species, especially in stress measurement; therefore, more extensive studies should be conducted, for instance, measuring biochemical parameters, such as cortisol. The participation of animals during complementary therapy for humans is a developing area. Dogs and horses are the most frequent partner species in animal-assisted services, but several unconventional species have also been involved, although there is a lack of information about the stress they experience caused by AAS. We conducted a comprehensive literature search, analyzing 135 articles with the purpose of investigating the effects of AAS on unconventional species such as guinea pigs, rabbits, farm animals, alpacas, donkeys, reptiles, aquarium fishes, and dolphins. We found that the relevant articles emphasize investigating the impact of animal-assisted interventions on humans, and they generally report positive outcomes. Limited data is available concerning the potential consequences the interventions may have on the animals. Therefore, it is our conclusion that more extensive studies should be conducted to get adequate information on stress experienced by animals during AAS, such as the measurement of biochemical parameters such as cortisol. Hence, meeting animal welfare considerations in addition to human interests could serve as a basis for the recommended methodology for therapies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Monoclonal antibodies (Ab) represent the fastest growing drug class. Knowledge of the biophysical parameters (kon, koff and KD) that dictate Ab:receptor interaction is critical during the drug discovery process. However, with the increasing complexity of Ab formats and their targets, it became apparent that existing technologies present limitations and are not always suitable to determine these parameters. Therefore, novel affinity determination methods represent an unmet assay need. Experimental Approach: We developed a pre‐equilibrium kinetic exclusion assay using recent mathematical advances to determine the kon, koff and KD of monoclonal Ab:receptor interactions on living cells. The assay is amenable to all human IgG1 and rabbit Abs. Key Results: Using our novel assay, we demonstrated for several monoclonal Ab:receptor pairs that the calculated kinetic rate constants were comparable with orthogonal methods that were lower throughput or more resource consuming. We ran simulations to predict the critical conditions to improve the performance of the assays. We further showed that this method could successfully be applied to both suspension and adherent cells. Finally, we demonstrated that kon and koff, but not KD, correlate with in vitro potency for a panel of monoclonal Abs. Conclusions and Implications: Our novel assay has the potential to systematically probe binding kinetics of monoclonal Abs to cells and can be incorporated in a screening cascade to identify new therapeutic candidates. Wide‐spread adoption of pre‐equilibrium assays using physiologically relevant systems will lead to a more holistic understanding of how Ab binding kinetics influence their potency. [ABSTRACT FROM AUTHOR]

Background: Many studies conducted on livestock point to fermented rapeseed meal (FRSM) as a component that provides adequate quality and quantity of protein. Additionally, it is a very good source of probiotics, prebiotics, enzymes, and antioxidants. A study was undertaken to assess the impact of a feed supplemented with FRSM fermented with Bacillus subtilis strain 87Y on production parameters, nutrient digestibility, and haematological and lipid indicators of the blood in growing rabbits. Forty New Zealand White rabbits (body weight 816,25 ± 24,98 g) aged 35 days were used in this study. The animals were divided into four groups, a control group (C) was fed a standard diet, while in the diet of three experimental groups, soybean meal (SBM) was replaced with FRSM at 4% (FR4 group), 8% (FR8 group), or 12% (FR12 group). Results: Detailed analysis revealed that the contribution of FRSM in the rabbit feed, regardless of the amount, had a significant effect on body weight gain (BWG), as well as average daily gain (ADG), compared to the control group (C), (P = 0.017). All groups receiving FRSM had a significantly lower (P = 0.05) feed conversion ratio (FCR) compared to the control group. In rabbits fed a diet containing 8% FRSM, the blood haematological parameters, such as red blood cells (RBC), haematocrit (HCT), haemoglobin (HGB), and mean corpuscular volume (MCV), were significantly higher compared to the control group (P = 0.037). In addition, a significant reduction in the plasma levels of the low-density lipoprotein fraction (LDL-chol), the ratio of total cholesterol to high-density lipoprotein (CHOL/HDL), (P = 0.001), and triacylglycerols (TG), (P = 0.004) were observed in the experimental groups compared to the control group. Conclusions: Based on the encouraging outcomes, it is possible to recommend domestically produced FRSM as a viable substitute for genetically-modified (GM) SBM in rabbit feed. [ABSTRACT FROM AUTHOR]

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits. Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA. Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR. Conclusions: CGMR might improve cartilage regeneration in osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: Oxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs. Methods: The predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations. Results: There were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007). Conclusions: An intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA. [ABSTRACT FROM AUTHOR]

Klebsiella is an encapsulated bacillus, a member of the family Enterobacteriaceae. Klebsiella can cause various illnesses, including pneumonia, bloodstream infections, urinary tract infections, and meningitis. Klebsiella has emerged as a nosocomial pathogen, particularly in premature infants and intensive care units (ICUs). This experiment aimed to investigate the toxic effects of K. pneumoniae on blood pictures and DNA structure. Thirty (30) male rabbits were divided into three groups. 1st group (GI) was given 1 milliliter/animal an oral dose of phosphate buffer saline (PBS) by a stomach tube as a control group for 60 days. The 2nd group (GII) was given one dose a week of 1 milliliter containing viable K. pneumoniae (1 X 106 CFU/ml) orally by stomach tube for 60 days. The 3rd group (GIII) was given the same dose twice a week. After 60 days, blood samples were collected from the heart and divided into 2 parts: 1st part for hematological analysis and 2nd part for detection of DNA damage using comet assay. The results of the hematological analysis showed significantly decreased RBCs, Hb and PCV, and considerably increased WBCs, lymphocytes, monocytes and neutrophils in the 2nd and 3rd groups, compared with the control group. In contrast, the comet assay showed DNA damage in the WBC of the different groups. The mean ± SE of tail length, tail intensity, tail moment and % DNA in the tail showed significant increases in the 2nd and 3rd groups, compared with the control group. [ABSTRACT FROM AUTHOR]

Background: Rabbits are the most important protein sources of animals for humans all over the world. Its production has increased significantly in recent years and it has become one of the most important animal sources in the Kingdom of Saudi Arabia. Coccidiosis is one of the most dangerous diseases affecting rabbits and other animals causing global economic losses. Plant extracts have been used as potential alternatives to chemotherapy because they do not have the negative consequences of tissue deposits and drug resistance. Methods: The current study examined the antioxidant activity of Vitis vinifera leaf extract (VVLE) in New Zealand rabbits infected with Eimeria stiedae. The extract was subjected to phytochemical analysis by FT-IR. A total of 35 male New Zealand rabbits were divided into seven groups. Group 1 served as the uninfected, untreated (negative control) group. Group 2 uninfected and treated at 400 mg/kg of extract to test for toxicity. Group 3 represented the infected, non-treated (positive control) group. While, groups 4, 5 and 6 comprised infected treated with at 100 mg/kg, 200 mg/kg and 400 mg/kg of extracts, respectively. Finally, group 7 consisted of infected rabbits treated with Toltrazuril at a dosage of 5 mg/kg body weight. Result: The analysis of phytochemicals by FT-IR for Vitis vinifera leaf extract revealed the existence of 15 biologically active compounds. VVLE was able to decrease the induced weight loss due to infection. Moreover, the oxidative status due to E. stiedae infection had been changed after treatment with VVLE where the level of glutathione, malondialdehyde and nitric oxide was improved indicating the antioxidant activity of the VVLE. Our findings suggested that VVLE could boost the induced oxidative stress in the liver of infected New Zealand rabbits, but studies are needed to determine the mechanism of VVLE. [ABSTRACT FROM AUTHOR]

The document "New Insights into Rabbit Viral Diseases" explores the impact of viruses on rabbit populations, focusing on myxoma virus (MYXV) and rabbit hemorrhagic disease virus (RHDV). It discusses the emergence of new genotypes of RHDV with expanded host ranges, affecting various hare species and American leporids. The document also highlights the role of rabbits in different ecosystems, as both keystone species and destructive pests, and the use of biocontrol methods like RHDV in managing rabbit populations. Additionally, it emphasizes the importance of citizen science in studying lagoviruses and developing effective control strategies. [Extracted from the article]

Purpose: Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [N-arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR). Methods: A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs. Results: The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18–5.00) at 2 h and 0.92 ppm (0.60–1.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was −5.1 mmHg⋅h (95% CI: −10 to 0.41) for control,−7.5 mmHg⋅h (95% CI: −14 to −1.1) for half-hourly acetaminophen, and −4.4 mmHg⋅h (95% CI: −14 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was −2.3 mmHg⋅h (95% CI: −5.9 to 1.3) for control,−2.0 mmHg⋅h (95% CI: −5.6 to 1.7) for AM404, −1.7 mmHg⋅h (95% CI: −4.5 to 1.2) for acetaminophen, and −3.2 mmHg⋅h (95% CI: −5.4 to −0.96) for acetaminophen/AM404 combined. Conclusions: Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsporidia are a group of fungus-related eukaryotes with worldwide distribution. The microsporidian species Encephalitozoon cuniculi and E. hellem occur in mammals, birds and even humans. Knowledge of their relevance in wild rabbits is very limited so far. Thus, the aim of the present study was to investigate the occurrence of E. cuniculi and E. hellem in wild rabbit populations in southern Germany (Bavaria). Therefore, blood and organ samples of 158 wild rabbits were investigated by serological and PCR-based assays. Antibodies to E. cuniculi were detected in 24 of the 158 (15.2%) wild rabbits, while DNA of E. cuniculi was found in 7 (4.4%) and DNA of E. hellem was found in 3 (1.9%). Sequencing identified E. cuniculi genotype 1. This study provides the first E. cuniculi genotype determination in free-living wild rabbits worldwide and the first evidence of E. hellem in rabbits worldwide. Wild rabbits should, therefore, be regarded as a reservoir for both pathogens and as a source of infection for domestic rabbits, other animals and humans. Encephalitozoon cuniculi and Encephalitozoon hellem are fungus-related, obligate intracellular pathogens belonging to the microsporidia. Both microorganisms occur in mammals, birds and even humans, thus revealing a zoonotic potential. Knowledge of their relevance in wild rabbits is very limited so far. Thus, the aim of the present study was to investigate the occurrence of E. cuniculi and E. hellem in wild rabbit populations in southern Germany (Bavaria). Therefore, blood and organ samples (brain/kidney) of 158 wild rabbits were investigated by immunofluorescence and PCR-based assays. Antibodies to E. cuniculi were detected in 24 of the 158 (15.2%) wild rabbits, while DNA of E. cuniculi was found in 7 (4.4%) and DNA of E. hellem was found in 3 (1.9%). Sequencing identified E. cuniculi genotype 1. This study provides the first E. cuniculi genotype determination in free-living wild rabbits worldwide and the first evidence of E. hellem in rabbits worldwide. Wild rabbits should, therefore, be regarded as a reservoir for both pathogens and, on the basis of molecular evidence from kidney tissue and presumed urine excretion, also as a source of infection for E. cuniculi for animals and humans. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the impact of the Encephalitozoon cuniculi on pet rabbits. It examines the link between antibody levels against this parasite and various health parameters in pet rabbits. By dividing 90 pet rabbits into healthy, subclinical, and clinical groups, this study carefully analyzed blood and biochemical changes. Key findings reveal that higher antibody levels in subclinical and clinical rabbits are crucial for diagnosis and management. This study also associates neurological signs and anemia with active infection, emphasizing the need for vigilant clinical and hematologic monitoring. The research found a higher infection rate in mature adult rabbits and a significant prevalence in Bangkok, indicating regional and age-related risk factors. Anemia was significantly linked to E. cuniculi infection, while no connections were found with other parameters. Recognizing anemia and neurological symptoms aids early diagnosis. Encephalitozoon cuniculi can cause serious disease and subclinical infection in rabbits and requires active surveillance to control the infection. This study investigated the association between anti-Encephalitozoon cuniculi antibody status and various health parameters in pet rabbits. A total of 90 rabbits were divided into healthy (N = 30), subclinical (N = 30), and clinical (N = 30) groups based on their anti-Encephalitozoon cuniculi antibody status and clinical presentations. The mean ages of the control (37 ± 40 months) and subclinical groups (38 ± 34 months) were notably lower compared to that of the clinical group (63 ± 38 months, p < 0.01). Serum titers for anti-Encephalitozoon cuniculi antibodies were significantly elevated in rabbits with subclinical and clinical infections compared to those of healthy rabbits (p < 0.05). Neurological signs were predominant in rabbits with active E. cuniculi infection (80.0%), with additional pathological features including urinary dysfunction (10.0%) and cataracts (10.0%). The source of rabbits was not associated with E. cuniculi infection (p = 0.159). Anemia was significantly linked to E. cuniculi infection (p = 0.026); however, no significant associations were found with leukocytosis, thrombocytopenia, or serum biochemistry parameters. Mature adult rabbits were more likely to be infected with E. cuniculi. Recognizing anemia and neurological signs facilitates in early diagnosis of E. cuniculi infection. [ABSTRACT FROM AUTHOR]

Introduction: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). Methods: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and gene set enrichment analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. Results: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells; however, it did not influence the proliferation of cells. RNA sequencing and gene set enrichment analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. Conclusions: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment. [ABSTRACT FROM AUTHOR]