NZW Rabbits Research Articles

The Efficacy of Topical Cefiderocol Treatment of Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis Is Dependent upon the State of the Corneal Epithelium.

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83-1.4 Log10 greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium.

Prosthetic Joint Infection Research Models in NZW Rabbits: Opportunities for Standardization-A Systematic Review.

Prosthetic joint infection (PJI) is a major complication following total arthroplasty. Rising antimicrobial resistance (AMR) to antibiotics will further increase therapeutic insufficiency. New antibacterial technologies are being developed to prevent PJI. In vivo models are still needed to bridge the translational gap to clinical implementation. Though rabbit models have been used most frequently, there is no consensus about methodology and measured outcomes. The PubMed, Scopus, and EMBASE databases were searched for literature on PJI in rabbit models. Data extraction included bias control, experimental design, and outcome measures of the NZW rabbit models in the articles. A total of 60 articles were included in this systematic literature review. The articles were divided into six groups based on the PJI intervention: no intervention used (21%), revision surgery (14%), prevention with only antibiotics (21%), prevention with surface modifications (7%), prevention with coatings (23%), and others (14%). Despite the current availability of guidelines and recommendations regarding experimental design, bias control, and outcome measures, many articles neglect to report on these matters. Ultimately, this analysis aims to assist researchers in determining suitable clinically relevant methodologies and outcome measures for in vivo PJI models using NZW rabbits to test new antimicrobial technologies.

Realtime assessment of vascular occlusion and reperfusion in animal models of intraoperative imaging- a pilot study.

Intraoperative monitoring of blood flow (BF) remains vital to guiding surgical decisions. Here, we report the use of SurgeON™ Blood Flow Monitor (BFM), a prototype system that attaches to surgical microscopes and implements laser speckle contrast imaging (LSCI) to noninvasively obtain and present vascular BF information in real-time within the microscope's eyepiece. The ability of SurgeON BFM to monitor BF status during reversible vascular occlusion procedures was investigated in two large animal models: occlusion of saphenous veins in six NZW rabbit hindlimbs and clipping of middle cerebral artery (MCA) branches in four Dorset sheep brain hemispheres. SurgeON BFM acquired, presented, and stored LSCI-based blood flow velocity index (BFVi) data and performed indocyanine green video angiography (ICG-VA) for corroboration. Stored BFVi data were analyzed for each phase: pre-occlusion (baseline), with the vessel occluded (occlusion), and after reversal of occlusion (re-perfusion). In saphenous veins, BFVi relative to baseline reduced to 5.2±3.7 % during occlusion and returned to 102.9±14.9 % during re-perfusion. Unlike ICG-VA, SurgeON BFM was able to monitor reduced BFVi and characterize re-perfusion robustly during five serial occlusion procedures conducted 2-5 min apart on the same vessel. Across four sheep MCA vessels, BFVi reduced to 18.6±7.7 % and returned to 120.1±27.8 % of baseline during occlusion and re-perfusion phases, respectively. SurgeON BFM can noninvasively monitor vascular occlusion status and provide intuitive visualization of BF information in real-time to an operating surgeon. This technology may find application in vascular, plastic, and neurovascular surgery.

Growth performance, plasma metabolites, meat quality, and meat and lipid health indices of New Zealand White rabbits as affected by dietary dried tomato pomace powder supplementation during the summer season.

One hundred and twenty New Zealand White rabbits (NZW) (5-week-old; 735.27 ± 27.23 g) were kept in an open-sided house during the summer season. The experiment aims to evaluate the impacts of dried tomato pomace powder (DTPP) supplementation on rabbits' performance, blood metabolites, carcass traits, meat quality, and lipid and health indices of NZW rabbits during 5-13 weeks of age. The four treatments were a standard rabbit feed (control) and the control diet supplemented with 0.5, 1.0, and 1.5% DTPP, respectively. Rabbits fed a diet containing 1.5% DTPP showed the highest growth rate through weeks 9-13 of age despite having the lowest feed intake spanning 5-13 weeks. The best feed conversion ratio (FCR) was recorded in rabbits fed with 1.5% DTPP-supplemented diet for 5-13 weeks. Diets supplemented with 0.5 or 1.0% DTPP enhanced markedly dressing %, total edible flesh, saturated (SFAs), monounsaturated (MUFAs), and polyunsaturated fatty acid (PUFAs) contents, as well as the ∑n - 6/∑n - 3 ratio and the total n - 6 of meat. Dietary supplementation with DTPP decreased kidney, abdominal, and back fat. Diets supplemented with DTTP decreased total cholesterol, triglycerides, and very low-density lipoprotein (vLDL) concentrations. The greatest levels of linoleic acid, arachidonic and water-holding capacity in meat were observed in rabbits fed 1.5% DTPP-supplemented diets. Diets containing 1 and 1.5% DTPP improved meats' atherogenic and thrombogenic indices, meat lipid quality desired fatty acids/undesired fatty acids ratio, and meat health index. Conclusively, DTPP up to 1.5% maintained the growth performance of rabbits, boosted meat quality through increasing vitamin E, reduced fat deposition, modified fatty acid composition, and improved atherogenic, thrombogenic, and hypocholesterolemic indices of rabbit meat.

INFLUENCE OF MG-CYLINDERS ON BONE AND CARTILAGE IN OSTEOARTHRITIS

There are no efficient treatment options for osteoarthritis (OA) that delay further progression. Besides osteoinduction, there is growing evidence of also anti-inflammatory, angiogenetic and neuroprotective effects of biodegradable magnesium-based biomaterials. Their use for the treatment of cartilage lesions in contrast is not well-evaluated yet.Mg-cylinders were analysed in an in vitro and in vivo OA model. In vitro, SCP-1 stem cell line was analysed under inflammatory conditions and Mg-impact. In vivo, small Mg- and WE43 alloy-cylinders (1mm × 0,5mm) were implanted into the subchondral bone of the knee joint of 24 NZW rabbits after establishment of OA. As control, another 12 rabbits received only drill-holes. µCT-scan were performed and assessed for changes in bone volume and density. After euthanasia, cartilage was evaluated macroscopically and histologically after Safranin-O-staining. Furthermore, staining with CD271 directed antibody was performed to assess neuro-reactivity.In vitro, an increased gene expression of extracellular matrix proteins as collagen II or aggrecan even under inflammatory conditions was observed under Mg-impact. In vivo, µCT evaluation revealed twice-elevated values for bone volume in femoral condyles with Mg-cylinders compared to controls while density remained unchanged. Cartilage showed no significant differences between the groups. Mg- and WE-samples showed significantly lower levels of CD271+ cells in the cartilage and bone of the operated joints than in non-operated joints, which was not the case in the Drilling-group. Furthermore, bone in operated knees of Drilling-group showed a strong trend to an increase in CD271+ cells compared to both Cylinder-groups. Counting of CD271+ vessels revealed that this difference was attributable to a higher amount of these vessels.The in vitro results indicate a potential cartilage regenerative activity of the degradable Mg-based material. While so far there was no positive effect on the cartilage itself in vivo, implantation of Mg-cylinders seemed to reduce pain-mediating vessels.Acknowledgements: This work is funded by the German Research Foundation (DFG, project number 404534760). We thank Björn Wiese for production of the cylinders.

Modifications of long-term heart rate variability produced in an experimental model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) has been linked to a higher prevalence of cardiac arrhythmias, the most frequent being atrial fibrillation, but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic nervous system activity, which can be quantified by analysing heart rate variability (HRV). Our aim was to investigate the modifications of long-term HRV in an experimental model of diet-induced MetS to identify the early changes in HRV and the link between autonomic dysregulation and MetS components. NZW rabbits were randomly assigned to control (n = 10) or MetS (n = 10) groups, fed 28 weeks with high-fat, high-sucrose diet. 24-hour recordings were used to analyse HRV at week 28 using time-domain, frequency-domain and nonlinear analyses. Time-domain analysis showed a decrease in RR interval and triangular index (Ti). In the frequency domain, we found a decrease in the low frequency band. Nonlinear analyses showed a decrease in DFA-α1 and DFA-α2 (detrended fluctuations analysis) and maximum multiscale entropy. The strongest association between HRV parameters and markers of MetS was found between Ti and mean arterial pressure, and Ti and left atrial diameter, which could point towards the initial changes induced by the autonomic imbalance in MetS.

2557. Development of Rabbit Models of Ventilator-Associated Carbapenem-Resistant Acinetobacter baumannii Pneumonia

Abstract Background Carbapenem-resistant (CR) Gram-negative bacteria are emerging worldwide as global public health threats. Mortality rates from these pathogens are especially high in immunocompromised patients. Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of CR Gram-negative bacterial infections. We therefore aimed to develop rabbit animal models of VABP caused by CR strains of Acinetobacter baumannii. Methods Persistently neutropenic NZW rabbits were used throughout the study. A novel endotracheal tracheostomy system was developed for intubation. The early-phase intubated model (0-24h) received mechanical ventilation, while the late-phase intubated model (72-96h) was ambulatory. Ventilators were set to FiO2=40% and PEEP=8mmHg. The following outcome variables were assessed: survival, residual tissue bacterial burden (log CFU/g), residual BAL bacterial burden (log CFU/mL), lung weights, pulmonary lesion score, histology, pulse O2 saturation, radiographic imaging, pro-inflammatory cytokines, quantitative tissue and BAL PCR, and histology. Results Within the first 12h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, which were established at approximately 106 CFU/g and 105 CFU/mL, persisted through 24h in the early-phase model and were increased in the late-phase model (72-96h) to approximately 107 CFU/g, and 106 CFU/mL. Mean Max SpO2 was ≥99 mmHg and mean nadir SpO2 was ≥74 mmHg. Serial thoracic radiographs over the course of 12-96h demonstrated progressive multilobar pneumonic infiltrates, while lung histology revealed progressive development of focal bronchopneumonia, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, macrophage activation, monocytic infiltration, alveolar septal disruption, and microcolonies of bacteria. Conclusion The new rabbit model of VABP produced by CR A. baumannii recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection. Disclosures All Authors: No reported disclosures

Insufficient arterial driving pressure turns hypoxic microvascular remodeling into a catastrophe

Abstract The tissue microvasculature is known to remodel in response to ischemia. However, the benefit or harm of this process is not completely understood and may limit also the potential of taking control of ischemic diseases that remain the leading cause of death worldwide. In a series of clinical and preclinical studies, we have thus dissected the biological relevance and the pathomechanistic role of hypoxic microvascular remodeling in critical limb threatening ischemia (CLTI). High-resolution contrast enhanced ultrasound was used in 50 patients with severe CLTI scheduled for immediate revascularization to study ischemic muscle microvascular blood flow. Immunohistological analyses were performed for amputation muscle samples from a set of 40 CLTI patients to analyze microvascular changes with respect to the level of myofiber atrophy. Furthermore, the amputation muscle samples were used to find 3 paired samples from 20 patients representing microvascular transformation along worsening of ischemic muscle damage, and used for RNA sequencing to analyze mechanisms of microvascular transformation. Additionally, animal models for acute ischemia in C57Bl-mice (n=42) and hypercholesterolemic LDLR-/-ApoB100/100 mice (n=61) and chronic CLTI-like ischemia model in cholesterol-fed NZW rabbits (n=24) with AdVEGF-A or AdLacZ control gene transfer were employed to study: 1) the natural course of microvascular changes leading to efficient muscle regeneration; 2) the effect of reduced arterial driving pressure on muscle regeneration; and 3) the effect of reduced arterial driving pressure and microvascular transformation on muscle regeneration, respectively. Decreased capillary transit time (P&amp;lt;0.01) and a gradual arterialization of capillaries along worsening of ischemic tissue damage (P&amp;lt;0.001) were observed in CLTI muscle. CLTI muscle RNA sequencing further suggested that the capillary arterialization process is an orchestration of different growth factors, cell types and even physical forces in the hypoxic muscle. Furthermore, animal models of acute and chronic limb ischemia display post-ischemic capillary enlargement (P&amp;lt;0.05) as a primary microvascular modification that facilitates collateral maturation but under decreased arterial driving pressure can turn from a good intention to aggravating ischemic damage. These results depict a critical role for the microvasculature in determining ischemic muscle outcome after an initial arterial occlusion in CLTI. Hypoxic microvascular remodeling, according to this data, initially has a good purpose but can also cause harm given enough time and the wrong environment. Moreover, these results offer understanding to the differential natural recoveries of experimental animals and human patients from an ischemic exposure – information that is essential for designing better treatments for ischemic diseases.

Topical Losartan Decreases Myofibroblast Generation But Not Corneal Opacity After Surface Blast-Simulating Irregular PTK in Rabbits.

To evaluate the efficacy of topical losartan after blast injury-simulating irregular phototherapeutic keratectomy (PTK) in rabbits. Twelve NZW rabbits underwent 100 pulse 6.5mm diameter PTK over a metal screen to generate severe surface irregularity and inhibit epithelial basement membrane regeneration. Corneas were treated with 0.8mg/mL losartan in balanced salt solution (BSS) or BSS 50 µL six times per day for six weeks after PTK. All corneas had slit lamp photography, with and without 1% fluorescein at two, four, and six weeks after PTK, and were analyzed using immunohistochemistry for the myofibroblast marker α-smooth muscle actin (α-SMA), keratocyte marker keratocan, mesenchymal cell marker vimentin, transforming growth factor (TGF)-β1, and collagen type IV. Topical 0.8mg/mL losartan six times a day significantly decreased anterior stromal α-SMA intensity units compared to BSS at six weeks after anterior stromal irregularity-inducing screened PTK (P = 0.009). Central corneal opacity, however, was not significantly different between the two groups. Keratocan, vimentin, TGF-β1, or collagen type IV levels in the anterior stroma were not significantly different between the two groups. Topical losartan effectively decreased myofibroblast generation after surface blast simulation irregular PTK. However, these results suggest initial masking-smoothing PTK, along with adjuvant topical losartan therapy, may be needed to decrease corneal stromal opacity after traumatic injuries that produce severe surface irregularity. Topical losartan decreased scar-producing stromal myofibroblasts after irregular PTK over a metal screen but early smoothing of irregularity would also likely be needed to significantly decrease corneal opacity.

Epitope-Specific Anti-SerpinB3 Antibodies for SerpinB3 Recognition and Biological Activity Inhibition.

SerpinB3 is a serine protease inhibitor that plays a relevant role in disease progression and cancer by increasing fibrosis, cell proliferation, and invasion, besides conferring resistance to apoptosis. The mechanisms underlying these biological activities are not yet fully understood. The aim of this study was to generate antibodies directed against different SerpinB3 epitopes to better investigate their biological role. Five exposed epitopes were identified using the software DNASTAR Lasergene and the corresponding synthetic peptides were used for NZW rabbit immunization. Anti-P#2 and anti-P#4 antibodies were able to recognize both SerpinB3 and SerpinB4 by ELISA. Anti-P#5 antibody, produced against the reactive site loop of SerpinB3, showed the greatest specific reactivity for human SerpinB3. This antibody was able to recognize SerpinB3 at nuclear level, while anti-P#3 antibody recognized SerpinB3 only at cytoplasmic level, both by immunofluorescence and by immunohistochemistry. The biological activity of each antibody preparation was assessed in HepG2 cells overexpressing SerpinB3 and anti-P#5 antibody reduced proliferation by 12% cell and cell invasion by 75%, while trivial results were obtained with the other antibody preparations. These findings indicate that the reactive site loop of SerpinB3 is essential for the invasiveness features induced by this serpin and it could become a novel druggable target.

Deproteinized Bone Tissue as a Matrix for Tissue-Engineered Construction: Experimental Study

Background. At present, for a number of reasons the complete bone defect replacement with autogenous bone is not always possible. Bone substitute materials are used as an alternative to autogenous bone tissue and can be of either biological or non-biological origin. One of the ways of development of reconstructive technologies is the use of tissue-engineered constructs that fully imitate autogenous bone tissue in the required volume.&#x0D; Aim of study to define in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs.&#x0D; Methods. An in vivo study was carried out on NZW rabbits. To create a construct, we used the fragments of deproteinized cancellous bone tissue of the human femoral head and stromal vascular fraction of rabbit adipose tissue as a matrix. Bone defect modeling with its subsequent replacement was performed to evaluate the efficacy of reparative osteogenesis during bone defects reconstruction. Study groups were defined: group 1 (control) surgical modeling of a bone defect of the femur without its reconstruction; group 2 surgical modeling of a bone defect of the femur with its reconstruction using fragments of deproteinized cancellous bone matrix; group 3 surgical modeling of a bone defect of the femur with its reconstruction using fragments of deproteinized cancellous bone matrix in combination with stromal vascular fraction of adipose tissue (according to ACP SVF technology).&#x0D; Results. Comparative analysis of reparative processes in case of applying tissue-engineered constructs based on deproteinized human cancellous bone matrix in combination with adipose tissue-derived stromal vascular fraction on in vivo experimental model revealed that the use of these bone substitute materials contributes not only to an early activation of reparative regeneration of main structural elements of the bone tissue in the area of the bone defect replacement, but also to its well-timed differentiation. This determines the restoration of structural and functional viability of the bone tissue at the damage site without developing discernible reactive inflammation. Moreover, the effect of the selected tissue-engineered construct with the combined influence of several factors (ACP SVF) in its composition turned out to be more effective in stimulating bone tissue repair and differentiation.&#x0D; Conclusion. Combination of SVF and deproteinized bone matrix for creating tissue-engineered constructs enables to engage several regeneration mechanisms and accelerate the process of bone defect replacement in comparison with isolated deproteinized bone matrix without bone defect reconstruction.

Ranpirnase (OKG-0301), a Novel Ribonuclease, Demonstrates Antiviral Activity against Adenovirus in the Ad5/NZW Rabbit Ocular Replication Model.

Adenovirus ocular infections are common ocular viral infections seen worldwide, for which there is no approved antiviral therapy available. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA resulting in an inhibition of protein synthesis. The study goal was to determine the anti-adenoviral activity of topical formulations of ranpirnase (OKG-0301) on adenoviral replication in the Ad5/NZW rabbit ocular replication model. NZW rabbits were inoculated in both eyes with human adenovirus type 5 (HAdV5) after corneal scarification. A day later, topical therapy was initiated in both eyes with 0.03% OKG-0301, 0.003% OKG-0301, saline or 0.5% cidofovir. Eyes were cultured to determine HAdV5 eye titers over 2 weeks. OKG-0301 (0.03% and 0.003%) and 0.5% cidofovir decreased viral titers compared to saline. Furthermore, both OKG-0301 formulations and 0.5% cidofovir shortened the duration of the HAdV5 infection compared to saline. Both 0.03% OKG-0301 and 0.003% OKG-0301 demonstrated increased antiviral activity compared to saline in the Ad5/NZW rabbit ocular replication model. The antiviral activity of the OKG-0301 groups was similar to that of the positive antiviral control, 0.5% cidofovir. Ranpirnase (OKG-0301) may be a potential candidate for a topical antiviral for adenoviral eye infections. Further clinical development is warranted.

Antioxidants status and physiological responses to early and late heat stress in two rabbit breeds.

Early life heat stress negatively affects rabbit production and well-being. However, the physiological response to acute heat stress in later life is not clearly defined. The present study aims to investigate the effects of early and late heat stress at 36°C on some blood constituents, antioxidant enzymes activity in the blood, and muscle in New Zealand white and Baladi Black rabbits. A total of sixty post-weaning rabbits of each breed were randomly divided into two groups; control groups (NZWC and BBC) and early heat-stressed groups for six hours at 36 ± 1°C and 62% relative humidity (RH) (NZWT and BBT groups). After heat stress, six rabbits from each group were slaughtered for blood and muscle tissue collection. The surviving rabbits were kept at 28 ± 1°C and 40% RH till 13 weeks of age. At the end of 13 weeks, all rabbits were exposed to late heat stress as precious described to perform four groups: single late stressed groups; NZWC2, BBC2, and double stressed groups; NZWT2 and BBT2. After late heat stress, six rabbits from each group were slaughtered for blood and muscle tissue collection. The early and late heat stress caused a significant reduction in the blood creatine kinase, lactate dehydrogenase, and high-density lipoprotein and antioxidant enzymes' activity in blood and muscle of both NZW and BB rabbits compared with the control groups. While, the blood total cholesterol, triglycerides, total lipids levels, and lipid peroxidation activity in blood and muscle were significantly increased due to the early and late heat-stressed both breeds compared with the control groups. It could be concluded that the early heat stress at 36°C has negative effects on several physiological indicators and antioxidant activities in the blood and muscle of NZW and BB rabbits.

Developmental and reproduction toxicity of piperonyl butoxide part 2 developmental safety of piperonyl butoxide in the NZW rabbit

Piperonyl butoxide (PBO) was developed in the 1940s. PBO increases the effectiveness of pyrethrins, thus it is called a synergist. Herein, the findings from a guideline developmental toxicity study in rabbits conducted in 1986 are reported. Inseminated New Zealand White rabbits were randomly assigned to a control and three treatment groups of 16 does each. Dose levels of 50, 100 and 200 mg/kg/day were selected based on a dosage-range study to avoid excessive maternal toxicity and administered orally (gavage) as a single daily dose on days 7–19 of gestation at a volume of 0.5 mL/kg. The control group received the vehicle only, Mazola® corn oil. Cesarean sections were performed on all surviving females on gestation day 29 and fetuses were evaluated. Survival for all study groups was 100%. Treatment-related maternotoxicity was manifested at the 100 and 200 mg/kg/day levels as decreased defecation and dose-related body weight losses during the treatment period (gestation days 7–13 and 7–19). The Cesarean section parameter values and fetal morphological observations of the treated groups did not differ significantly from the concurrent control group and were within the historical control range for this rabbit strain. No maternal or fetal adverse effects were seen at the 50 mg/kg/day dose level. Although maternal toxicity resulting from treatment was apparent at the 100 and 200 mg/kg/day dose levels, neither fetotoxicity nor teratogenicity were elicited in rabbits by piperonyl butoxide at dose levels as high as 200 mg/kg/day.

Study about animal (NZW Rabbit, Juvenile pig) test to secure safety and effectiveness of thermoplastic polyurethane stent graft &amp; graft using electrospinning

Background. A stent is a cylindrical medical device used to normalize the flow of blood or body fluids, such as blood vessels, gastrointestinal tract, and bile duct, by inserting it into a narrowed or blocked area under image fluoroscopy without performing a surgical operation when the flow is not smooth. In particular, stents applied to blood vessels are divided into stents for coronary arteries, stents for blood vessels, stents for blood vessels in the brain, stents for iliac arteries, and stents made of absorbent materials. It is used to improve blood flow.Coronary artery disease refers to a lesion in which blood flow to the myocardium is impaired due to stenosis of the coronary arteries due to atherosclerosis. Atherosclerotic coronary artery disease has long been known as the most common cause of death in the West. Although it has not yet occurred frequently in the East, including Korea, it is reported that coronary artery disease is on the rise with the recent change in eating habits. Coronary artery disease is clinically manifested in one of three aspects: angina pectoris, myocardial infarction, and sudden death. Double myocardial infarction is usually caused by sudden thrombus in a coronary artery with atherosclerotic stenosis, resulting in complete blockage of myocardial blood flow. Myocardial infarction, which was supplied by blood vessels from blocked blood vessels, leads to necrosis. In order to improve blood flow in blood vessels blocked from blood supply due to myocardial infarction, stenting is in the spotlight along with surgical methods. Among the causes of blocking the flow of blood vessels, thrombus is seen as the main cause, so the frequency of using vascular stents with suppressed thrombus formation is increasing.Results. A coronary stent is a medical device used to improve blood flow by expanding a coronary artery narrowed by the formation of a thrombus, and is an intermediary procedure that minimizes side effects through surgery. Among the causes of blocking the flow of blood vessels, thrombus fish are seen as the main cause, so the frequency of using vascular stents with suppressed thrombus formation is increasing. S&amp;G Biotech Research Institute is developing a self-expanding Nitinol stent graft that can ensure patency while suppressing the formation of blood clots. The graft material used here is a material that hardly decomposes in bodily fluids such as blood by using a thermoplastic polyurethane material, and is loaded with an antithrombotic agent. Our research team produced a stent graft by spinning the TPU graft onto the self-expanding Nitinol stent skeleton with an electrospinning device, and confirmed its safety and effectiveness by conducting a biological safety evaluation and animal testing. In addition to the vascular stent for the coronary artery for the treatment of coronary artery disease, the frequency of application of the aortic vascular stent graft for the treatment of aortic vascular disease is also increasing. The aortic vascular stent graft is a stent composed of a metal stent skeleton and a graft and suture made of a biocompatible polymer material and is used for aortic dissection and aneurysm treatment.Conclusion. After blood vessel extraction, the surface of the inserted stent and the inside of the blood vessel were checked, and the result was grade 0 (no thrombus observed). No other peculiarities were identified inside the blood vessels. As a result of checking the H&amp;E results of 3 parts (distal part, middle part, and proximal part) of each blood vessel, in the stent group. Neointimal proliferation was not confirmed.Funding: This research was financially supported by the Ministry of Trade, Industry and Energy (MOTIE) and Korea Institute for Advancement of Technology (KIAT) through the International Cooperative R&amp;D program (Project No. P0016047).

RVSV-ΔG-SARS-CoV-2-S vaccine: repeated intramuscular (IM) toxicity, local tolerance, immunogenicity and biodistribution study in NZW rabbits.

BriLife®, a vector-based vaccine that utilizes the recombinant vesicular stomatitis virus (VSV) platform to express and present the spike antigen of SARS-CoV-2, is undergoing testing in a phase 2 clinical trial in Israel. A nonclinical repeated-dose (GLP) toxicity study in New Zealand white rabbits was performed to evaluate the potential toxicity, local tolerance, immunogenicity and biodistribution of the vaccine. rVSV-ΔG-SARS-CoV-2-S (or vehicle) was administered intramuscularly to two groups of animals (106, 107 PFU/animal, n = 10/sex/group) on three occasions, at 2-week intervals, followed by a 3-week recovery period. Systemic clinical signs, local reactions, body weight, body temperature, food consumption, ophthalmology, urinalysis, clinical pathology, C-reactive protein, viremia and antibody levels were monitored. Gross pathology was performed, followed by organs/tissues collection for biodistribution and histopathological evaluation. Treatment-related changes were restricted to multifocal minimal myofiber necrosis at the injection sites, and increased lymphocytic cellularity in the iliac and mesenteric lymph nodes and in the spleen. These changes were considered related to the inflammatory reaction elicited, and correlated with a trend for recovery. Detection of rVSV-ΔG-SARS-CoV-2-S vaccine RNA was noted in the regional iliac lymph node in animals assigned to the high-dose group, at both termination time points. A significant increase in binding and neutralizing antibody titers was observed following vaccination at both vaccine doses. In view of the findings, it was concluded that the rVSV-ΔG-SARS-CoV-2-S vaccine is safe. These results supported the initiation of clinical trials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00204-022-03302-5.

Nano-Selenium Effect on Sexual Hormones and Enzymatic Activity in Relation to Sexual Puberty in NZW Rabbits

Nano-Selenium Effect on Sexual Hormones and Enzymatic Activity in Relation to Sexual Puberty in NZW Rabbits

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

PurposeMicroencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin.MethodsAn S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed.ResultsThe microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis.ConclusionThe in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

Evaluating Maternal Exposure to an Environmental Per and Polyfluoroalkyl Substances (Pfas) Mixture During Pregnancy: Adverse Maternal and Fetoplacental Effects in a New Zealand White (Nzw) Rabbit Model

Evaluating Maternal Exposure to an Environmental Per and Polyfluoroalkyl Substances (Pfas) Mixture During Pregnancy: Adverse Maternal and Fetoplacental Effects in a New Zealand White (Nzw) Rabbit Model

The Influence of Dietary Zinc Oxide Nanoparticles on Zootechnical Performance and Biometric Indices of Growing New Zealand White Rabbits

This study was designed to compare the effects of dietary conventional inorganic Zinc oxide (ZnO) and nano-zinc oxide (ZnO-NPs) on the zootechnical performance, selected blood serum indices, antioxidant status, general health and production of rabbit meat enriched with zinc enriched with nano-zinc in growing New Zealand White rabbits (NZW). A total of 481 newly-born rabbits produced from two natural successive mating between 36 primiparous (NZW) Rabbit does and 12 bucks by the intensive breeding system were utilized throughout this study. Rabbits does and bucks were randomly distributed into four equal groups, the control positive group G1 was fed the basal diet supplemented with premix contain 50 ppm inorganic zinc in the form of ZnO; while the control negative G2 was fed on a basal diet supplemented with Zinc Free premix, meanwhile, G3 was fed on the basal diet supplemented with premix contain 25 ppm nano zinc as zinc oxide nanoparticles, however, G4 was fed on the basal diet supplemented with 50 ppm nano zinc as zinc oxide nanoparticles in the premix, Litters after weaning continued on the same diet like their dams till the age of selling at 62 days old. The results showed that the growing rabbits in (G4) supplemented with 50 mg ZnO-NPs/kg diet surpassing significance (P≤ 0.05) in all groups and achieved the best result regarding (birth weight(g), weaning weight(g), sealing weight (g) moreover lower Pre-weaning mortality %, and Post-weaning mortality%). Also, G4 showed significant improvement in FCR in comparison with other groups. Furthermore, showed highest significant increase in total protein and globulin, HDL, SOD, GSH, Catalase activity, and zinc concentration in serum, liver, and thigh tissue and also showed the highest significant decrease in AG ratio, creatinine, urea, uric acid, cholesterol, Triglyceride, LDL, VLDL, risk factor, MDA and NO level in G4 at 62 day age old, compared to other groups, while there was no significant difference in albumin level between all the experimental groups. In conclusion, supplementation of 50 mg ZnO-Npskg diet in the premix to the diet of growing NZW rabbit maximize the productive performance and improve FCR without any adverse effect.