New Zealand White Research Articles

Long-Term Endurance Exercise Training Alters Repolarization in a New Rabbit Athlete's Heart Model.

In the present study, the effect of long-term exercise training was investigated on myocardial morphological and functional remodeling and on proarrhythmic sensitivity in a rabbit athlete’s heart model. New-Zealand white rabbits were trained during a 12-week long treadmill running protocol and compared with their sedentary controls. At the end of the training protocol, echocardiography, in vivo and in vitro ECG recordings, proarrhythmic sensitivity with dofetilide (nM) were performed in isolated hearts, and action potential duration (APD) measurements at different potassium concentrations (4.5 and 2 mM) were made in the isolated papillary muscles. Expression levels of the slow component of delayed rectifier potassium current and fibrosis synthesis and degradation biomarkers were quantified. Echocardiography showed a significantly dilated left ventricle in the running rabbits. ECG PQ and RR intervals were significantly longer in the exercised group (79 ± 2 vs. 69 ± 2 ms and 325 ± 11 vs. 265 ± 6 ms, p < 0.05, respectively). The in vivo heart rate variability (HRV) (SD of root mean square: 5.2 ± 1.4 ms vs. 1.4 ± 0.2 ms, p < 0.05) and Tpeak-Tend variability were higher in the running rabbits. Bradycardia disappeared in the exercised group in vitro. Dofetilide tended to increase the QTc interval in a greater extent, and significantly increased the number of arrhythmic beats in the trained animals in vitro. APD was longer in the exercised group at a low potassium level. Real-time quantitative PCR (RT-qPCR) showed significantly greater messenger RNA expression of fibrotic biomarkers in the exercised group. Increased repolarization variability and higher arrhythmia incidences, lengthened APD at a low potassium level, increased fibrotic biomarker gene expressions may indicate higher sensitivity of the rabbit “athlete’s heart” to life-threatening arrhythmias.

Effect of Dietary Rosemary and Ginger Essential Oils on the Growth Performance, Feed Utilization, Meat Nutritive Value, Blood Biochemicals, and Redox Status of Growing NZW Rabbits.

Simple SummaryThe rabbit farming industry has gained more interest due to its high productivity, high growth rate, and high-quality meat. One of the public health concerns is that global rabbit production is expected to increase to meet the increasing demand for lean meat. In the present study, we focused on the use of phytogenic feed additives (essential oils of rosemary (REO) and ginger (GEO)) as environmentally friendly supplementation to improve rabbit growth performance, physiological status, and meat quality. The results indicated that the use of REO and GEO at a dose of 0.5% dramatically improved the growth performance and feed utilization of treated rabbits. The cholesterol level decreased significantly in rabbit plasma and meat after REO and GEO treatments. The fat content tended to decline in the muscles and the triglycerides were remarkedly reduced in the plasma of treated animals. In addition, the oxidant/antioxidant balance in the plasma could be improved with supplementation with a high dose of REO and GEO. Accordingly, the use of REO and GEO as supplementations for growing rabbits could contribute to improving the sustainable production of the rabbit industry.This study was conducted to assess the impacts of using two essential oils, rosemary and ginger, on growing rabbits’ performance, carcass traits, meat composition, blood biochemicals, and the redox status of growing New Zealand White (NZW) rabbits. A total of 120 unsexed NZW rabbits, 42-days-old, were assigned randomly to five experimental groups (n = 24, 6 replicates with 4 rabbits each). The first group received a basal diet (control), the second to fifth groups were dietary supplemented daily with rosemary essential oil (REO) and ginger essential oil (GEO) at doses of 0.25 and 0.5% for each supplementation (REO-0.25, REO-0.5, GEO-0.25, and GEO-0.5), respectively. The growth traits were studied for 7 weeks, from the 7th to the 13th week of the rabbits’ age. The results revealed that final body weight, weight gain, and average daily gain increased significantly (p < 0.01) in the REO-0.5 and GEO-0.5 treatments compared to the control group. Daily feed intake decreased (p = 0.005) in essential oil treatments. Meanwhile, the feed conversion ratio improved significantly (p = 0.001) in REO and GEO at the high doses compared to the control group. The weight percentages of liver and giblets increased (p < 0.001) with both treatments of REO and GEO compared to the control group. The dietary supplementation with REO and GEO did not affect (p > 0.05) the meat composition of Longissimus dorsi and hind leg muscles. Meanwhile, REO and GEO supplementation significantly decreased cholesterol levels in the rabbit meat. Thiobarbituric acid reactive substance concentrations decreased by 10 and 15% in the meat of REO-0.5 and GEO-0.5 treatments, respectively, compared to the other groups. In the same trend, REO and GEO treatments induced a significant (p = 0.001) reduction in the plasma cholesterol concentrations and triglycerides compared to the control. The total antioxidant capacity increased by 7.60% and the malondialdehyde decreased by 11.64% in the plasma of GEO-0.5 treatment than the control. Thus, the dietary supplementation of REO and GEO have a beneficial effect in improving the productivity and meat quality of growing rabbits.

A Novel Eye Drop Formulation for Potential Treatment of Neovascular Age-Related Macular Degeneration.

PurposeDrug delivery to posterior ocular tissues via topical eye drop administration is arduous due to the unique anatomy and physiology of the eye. Therefore, treatments for posterior eye disease have to be administered via intravitreal injection or systemic route, both of which have their drawbacks. Herein, the objective of this work was to demonstrate that a specially designed eye drop formulation could effectively deliver small-molecule vascular endothelial growth factor (VEGF) inhibitor to posterior ocular tissues for antiangiogenic therapy.MethodsThe unique eye drop formulation, termed ITRI AXN eye drops, was obtained from self-assembly of (2-hydroxypropyl)-β-cyclodextrin with a VEGF tyrosine kinase inhibitor, a hydrophilic polymer, hypromellose, and a complex stabilizer, caffeine. In vivo ocular pharmacokinetics studies were performed with New Zealand White (NZW) rabbits and Non Human Primates (NHP). The antiangiogenesis effect was evaluated on the Long-Evans rat with laser-induced choroidal neovascularization and pigmented Dutch-Belted rabbits with VEGF-induced retinal neovascularization.ResultsThe successful drug transport from ocular surface to posterior ocular cavity was indicated by a drug biodistribution pattern in pharmacokinetic studies. Excellent drug exposure in the choroid and retina with the concentrations of 900- and 750-fold greater than drug IC50 0.5 hours post the eye drop administration (drug level: 0.8%) was observed on the NHP study. The obtained formulation also demonstrated a comparable antiangiogenic outcome with the intravitreal injection of anti-VEGF antibody on rat and rabbit disease models.ConclusionsOur eye drop formulation has demonstrated great promise in antiangiogenic therapy against retinal and choroidal neovascularization in animal models. The results suggest that the aim of this work can be successfully achieved by the novel eye drop formulation.Translational RelevanceThe preclinical results provide evidence that ITRI AXN eye drops could effectively deliver therapeutics to the choroid and retina for antiangiogenic therapy.

Annona muricata L. Suppresses Stannous Chloride Effects through Changing Hematological Parameters in Male New Zealand White Rabbits

Background: Annona muricata. L has a wide range of therapeutic characteristics and is frequently used in traditional medicine to treat a variety of ailments. Stannous chloride (SnCl2) are widely used in daily life and distributed in many tissues and nutrients. Although over-ingestion of SnCl2, can cause health problems, relatively little attention has been given to the toxic effects of this compound in livestock health and hematological parameters. This study was designed to study protective roles of A. muricata L. against SnCl2 effects through alleviating hematological disturbances in adult male New-Zealand white rabbits.&#x0D; Materials and Methods: Four rabbits per group were assigned to 1 of 4 treatment groups: 0 mg A. muricata and 0 mg SnCl2/kg BW (control); 100 mg of A. muricata /kg BW; 20 mg SnCl2/kg BW; 20 mg SnCl2 plus 100 mg of A. muricata /kg BW. Rabbits were orally administered the respective doses every other day for 10 weeks.&#x0D; Results: The obtained results showed that A. muricata alone caused increase in body weight, relative weight of liver, lung, heart and kidney. It also caused increase hemoglobin (Hb), packed cell volume (PCV) level and number of platelets (PLT) compared to control. However, treatment with A. muricata was caused significant decrease in white blood cell counts (WBCs) and non-significant decrease in red blood cell counts (RBCs), mean cell volume (MCV). Meanwhile, treatment with SnCl2 was lead to adverse effect on the body weight and relative organs weight practically spleen. It was caused significant increase in WBCs, MCV compared to control. The rest of hematological parameters (RBCs, PCV, PLT, Hb and MCHC) were significantly decreased, which indicated to cause anemia. Previous parameters were returned to normal values in group that treatment with A. muricata plus SnCl2. In term of bone marrow smear, all smears are similar in terms of numbers and types of cells.&#x0D; Conclusion: Results of the present study convincingly demonstrated that SnCl2 exposure resulted in varying degree of hematological parameters of rabbits. A. muricata has been promise as nutritional supplements to help prevent disorders involving SnCl2 induced these effects. Thus A. muricata may be helpful to combat SnCl2 associated sufferings in human as well as animal.

1047. Development of a Next Generation 30+ Valent Pneumococcal Conjugate Vaccine (VAX-XP) Using Site-Specific Carrier Protein Conjugation

BackgroundDue to the diversity of serotypes, exacerbated by the phenomenon of serotype replacement, there remains an unmet medical need for a pneumococcal conjugate vaccine (PCV) containing additional serotypes. Using a cell-free protein synthesis (CFPS) platform to produce an enhanced carrier protein (eCRM®) based on the CRM197 sequence, Vaxcyte is developing a PCV encompassing over 30 serotypes. The eCRM carrier protein contains multiple insertions of the non-native amino acid para-azidomethyl-L-phenylalanine (pAMF) that facilitates site-specific conjugation of the pneumococcal polysaccharides (PS) to eCRM. Unlike conventional methodologies, site-selective conjugation enhances process consistency and increases capacity for inclusion of additional serotypes in a PCV without promoting carrier suppression. Using this platform, the aim of the current study was to employ CFPS technology to construct a 31-valent PCV and evaluate its immunogenicity in New Zealand White (NZW) rabbits. MethodsThe eCRM carrier protein was individually conjugated to each of 31 selected pneumococcal PSs using copper-free click chemistry to produce 31 Conjugate Drug Substances (DS), which were then mixed with aluminum phosphate to produce the VAX-XP Drug Product. 24 of the DS conjugates in VAX-XP were generated at manufacturing scale. Two doses of VAX-XP were administered to NZW rabbits at 0 and 21 days to assess its ability to elicit anti-capsular IgG antibodies. Additionally, rabbits were also administered either Prevnar13 or a mixture of Pneumovax 23 and 8 incremental PS in isotonic saline, as comparators.ResultsVAX-XP showed conjugate-like immune responses for all 31 serotypes, as demonstrated by superior responses to PS-based vaccines and comparable responses to Prevnar13. IgG responses for VAX-XP compared with Prevnar13 and Pneumovax 23 at 14 days post dose 2 ConclusionThese results demonstrate that increasing the number of pneumococcal serotypes does not result in immunological attenuation in any of the serotypes contained in VAX-XP relative to the current standard of care. Furthermore, the data confirm the scalability and reproducibility of the CFPS platform in the production of VAX-XP conjugates, creating the foundation for a next generation broad-valency PCV.Disclosures Chris Behrens, PhD, Vaxcyte, Inc. (Employee) Jeff Fairman, PhD, Vaxcyte, Inc. (Employee) Paresh Agarwal, PhD, Vaxcyte, Inc. (Employee) Shylaja Arulkumar, MS, Vaxcyte, Inc. (Employee) Sandrine Barbanel, MS, Vaxcyte, Inc. (Employee) Leslie Bautista, n/a, Vaxcyte, Inc. (Employee) Aym Berges, PhD, Vaxcyte, Inc. (Employee) John Burky, BS, Vaxcyte, Inc. (Employee) Peter Davey, MS, Vaxcyte, Inc. (Employee) Chris Grainger, PhD, Vaxcyte, Inc. (Employee) Sherry Guo, PhD, Vaxcyte, Inc. (Employee) Sam Iki, MS, Vaxcyte, Inc. (Employee) Mark Iverson, BS, Vaxcyte, Inc. (Employee) Neeraj Kapoor, PhD, Vaxcyte, Inc. (Employee) Olivier Marcq, PhD, Vaxcyte, Inc. (Employee) Thi-Sau Migone, PhD, Vaxcyte, Inc. (Employee) Lucy Pill, MS, Vaxcyte, Inc. (Employee) Mohammed Sardar, n/a, Vaxcyte, Inc. (Employee) Paul Sauer, MBA, Vaxcyte, Inc. (Employee) James Wassil, MS MBA, Vaxcyte, Inc. (Employee)

Intradiscal injection of monosodium iodoacetate induces intervertebral disc degeneration in an experimental rabbit model

BackgroundEstablishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. The intra-articular injection of monosodium iodoacetate (MIA), which is commonly used in animal models of osteoarthritis, induces cartilage degeneration and progressive arthritis in a dose- and time-dependent manner. The purpose of this study was to determine the effect of MIA injections into rabbit IVDs on the progression of IVD degeneration evaluated by radiographic, micro-computerized tomography (micro-CT), magnetic resonance imaging (MRI), and histological analyses.MethodsIn total, 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1–L2 to L4–L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1–L2: CA only; L2–L3: MIA 0.01 mg; L3–L4: 0.1 mg; L4–L5: 1.0 mg; L5–L6: non-injection (NI) control). Disc height was radiographically monitored biweekly until 12 weeks after injection. Six rabbits were sacrificed at 2, 4, 8, and 12 weeks post-injection and processed for micro-CT, MRI (T2-mapping), and histological analyses. Three-dimensional (3D) disc height in five anatomical zones was evaluated by 3D reconstruction of micro-CT data.ResultsDisc height of MIA-injected discs (L2–L3 to L4–L5) gradually decreased time-dependently (P < 0.0001). The disc height of MIA 0.01 mg-injected discs was significantly higher than those of MIA 0.1 and 1.0 mg-injected discs (P < 0.01, respectively). 3D micro-CT analysis showed the dose- and time-dependent decrease of 3D disc height of MIA-injected discs predominantly in the posterior annulus fibrosus (AF) zone. MRI T2 values of MIA 0.1 and 1.0 mg-injected discs were significantly decreased compared to those of CA and/or NI controls (P < 0.05). Histological analyses showed progressive time- and dose-degenerative changes in the discs injected with MIA (P < 0.01). MIA induced cell death in the rabbit nucleus pulposus with a high percentage, while the percentage of cell clones was low.ConclusionsThe results of this study showed, for the first time, that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs in a time- and dose-dependent manner. This study suggests that MIA injection into rabbit IVDs could be used as an animal model of IVD degeneration for developing future treatments.

Single cell RNA sequencing reveals ferritin as a key mediator of autoimmune pre-disposition in a mouse model of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a devastating autoimmune disorder characterized by failure of self-tolerance with resultant production of autoreactive antibodies. The etiology of this syndrome is complex, involving perturbations in immune cell signaling and development. The NZBWF1 mouse spontaneously develops a lupus-like syndrome and has been widely used as a model of SLE for over 60 years. The NZBWF1 model represents the F1 generation of a cross between New Zealand Black (NZB) and New Zealand White (NZW) mice. In order to better understand the factors that contribute to the development of autoimmunity, single cell RNA sequencing was conducted using the bone marrow from female NZBWF1 mice prior to the development of overt disease. The results were contrasted with single cell RNA sequencing results from the two parental strains. The expected findings of B cell abundance and upregulation, and evidence of interferon signaling were validated in this model. In addition, several novel areas of inquiry were identified. Most notably, the data showed a marked upregulation of the ferritin light chain across all cell types in the NZBWF1 mice compared to parental controls. This data can serve as a gene expression atlas of all hematopoietic cells in the NZBWF1 bone marrow prior to the development of autoimmunity.

A novel animal model for vulnerable atherosclerotic plaque: dehydrated ethanol lavage in the carotid artery of rabbits fed a Western diet.

The study of unstable atherosclerotic plaques is limited by the absence of ideal animal models to reproduce the plaque instability observed in humans. In this study, we attempted to develop a novel animal model for vulnerable atherosclerotic plaques using dehydrated ethanol lavage in rabbits fed a Western diet (WD). A total of 30 New Zealand White (NZW) rabbits were randomized to 5 groups, including a control group with or without WD, a balloon injury with WD group, and an ethanol injury with or without WD group. Operations were conducted using the right common carotid artery as the target vessel. All animals were followed up for 3 months unless a vascular event occurred. Blood samples and carotid artery specimens were ultimately collected for analysis of atherogenesis. Compared to rabbits in which lesions were induced by balloon injury, those subjected to an ethanol lavage with high cholesterol diet showed progressive atherosclerotic lesions in all carotid artery segments, which were characterized by greater plaque burden, smaller minimum lumen area (MLA), and increased vulnerability as indicated by abundant macrophages, scattered smooth muscle cell (SMC) composition, higher matrix metalloproteinase-9 (MMP-9) expression in plaques, thinner fibrous cap thickness, and higher possibility of stroke event (50% vs. 0%). Meanwhile, the serum interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) levels in the ethanol injury group with a high-cholesterol diet were significantly higher than those in the balloon injury group after 3 months (all P<0.01). We successfully established a novel animal model for vulnerable atherosclerosis by ethanol exposure of the carotid segment that has a higher predictive value for the probability of ischemic events than the balloon injury model. Therefore, it may represent a promising animal model for investigating new therapeutic approaches, novel imaging modalities, and underlying mechanisms for vulnerable atherosclerotic plaque.

Response of Carcass Characteristics of Growing White New Zealand Rabbit Fed on Different Biological Treated Roughages

The aim of the present study was to investigate the effect of feeding biological treated rice straw with Pleurotusostreatus or treated corn stalks with Trichodermareesei at different levels on carcass characteristics of rabbits. Dried treated rice straw (RS) or corn stalks (CS) were used to formulate the experimental pelleted diet by substituting of berseem hay with treated rice straw with medium only (without Pleurotusostreatus) and biological treated rice straw with Pleurotusostreatus (BTRS) or treated corn stalks with medium only (without Trichodermareesei) and biological treated corn stalks with Trichodermareesei (BTCS) at different levels. All diets were formulated to be iso-nitrogenous and iso-caloric, and to meet nutrients requirements for growing rabbits. A number of 78 weaned New-Zealand white rabbits about 6 weeks of age and weighed 500 g in average were randomly divided into 13 groups (R1 to R13) 6 rabbits in each. The experimental groups were fed as following the first group fed control diet (0% rice straw or corn stalks) and other 12 groups were fed on diets containing rice straw either with or without fungi or corn stalks either with or without fungi at 33, 66 and 100% as replacing of berseem hay (11, 22 and 33% of total diet). At the end of the experimental period (91 days), three rabbits from each group were slaughtered to evaluate carcass characteristics. The results showed that the values were significantly (P<0.05) higher with the slaughter weight (SW). The eviscerated body (EBW), carcass weight (CW1) and carcass weight and total giblets(CW2) with R13 (BTCS) ration and R6 ration were significantly (P<0.05) higher with CW1, CW2 and BTRS rations than other experimental rations. While SW, EBW, CW1 and CW2 were significantly lower with R2 (NBTRS) ration than other experimental rations. Values of the dressing percentage (DP1) showed that R6 (BTRS) ration was significantly higher while R3 (NBTRS) ration was significantly lower than other experimental rations. The values of the dressing percentage (DP3) showed that R10 (NBTCS) ration and R12 (BTCS) rations were significantly higher than other experimental rations. The average values of carcass cuts showed that R5 and R6 with (BTRS) rations were improved (P<0.05). The excellent carcass cuts weight (middle part than that of the control diet). It’s worthy to recommend the treated rice straw or corn stalks with fungi to be used to enhance carcass characteristics in rabbits’ diet.Conclusion : It was concluded that the treatment of rice straw with Pleurotusostreatus and corn stalks with Trichodermareesei (especially the replacement of berseem hay with 100% of the biological treated BTRS and BTCS) had beneficial returns on the carcass characteristics (traits) of the growing white New Zealand rabbits.

Potentiality of oregano essential oils as a growth modulator, immune enhancer and natural antioxidative in mite infested Newzealand white rabbits

Potentiality of oregano essential oils as a growth modulator, immune enhancer and natural antioxidative in mite infested Newzealand white rabbits

Abstract 10941: Cerebral Consumption of Lactate Increases Neurological Injury After Experimental Cardiac Arrest in Rabbits

Introduction: Neuronal consumption of lactate is known to be protective after long duration of brain ischaemia. However, its consequences on neurological function after shorter duration of ischemia like after cardiac arrest are unknown. Hypothesis: We hypothesized that cerebral lactate consumption is deleterious for neurological outcome, whereas lactate dehydrogenase inhibition by oxamate could improve recovery. Methods: Male New-Zealand rabbits were anesthetized and surgically instrumented to assess lactate, glucose and O 2 cerebral consumption by measurement of the arterio-jugular differences. After 10 min of ventricular fibrillation, animals were resuscitated and randomly received a 30-min infusion of either saline (Control, n=6), lactate (Lact, 5 mg/kg/min, n=6) or oxamate (Oxa, 37.5 mg/kg/min, n=6). They were followed during 4 h. Additional animals were submitted to the same procedure without surgical instrumentation to allow recovery and assessment of neurological function during 48 h after cardiac arrest. In both experiments, neuronal death was assessed histologically by fluorojade C staining. Results: In Control group, a strong increase of the cerebral consumption of O 2 , glucose and lactate was observed during the 4 hours following resuscitation. In Lact group, lactate consumption was increased as compared to Control, whereas it was almost abolished in Oxa group (17.13±3.59, 32.60±6.24 and 4.04±1.58 mmol/L/min in Control, Lact and Oxa, respectively). Additionally, Oxa group presented a reduced consumption of glucose and O 2 after cardiac arrest as compared to other groups. Interestingly, administration of oxamate was highly neuroprotective whereas lactate administration worsened the neurological outcome after cardiac arrest (38±4, 64±10 and 15±6 % of neurological dysfunction score at 48h in Control, Lact and Oxa, respectively). Oxamate infusion was also associated with a significant reduction in the number of degenerative neurons at 4 h and 48 h of follow-up. Conclusions: The cerebral consumption of lactate appeared to be detrimental in rabbits after cardiac arrest. Its inhibition by oxamate is potently neuroprotective.

Comparison of In Vivo and In Vitro Digestibility in Rabbits.

Simple SummaryWe tested the Ankom DaisyII Incubator as an alternative to the in vivo procedures for measuring the in vitro dry matter digestibility of diets for rabbits. The results were variable according to the methods. Among those tested in the trial, the enzymatic one was more effective than those based on fecal inocula. We conclude that the Ankom DaisyII Incubator can be used to estimate the in vivo dry matter digestibility of rabbit diets, but the choice of the method proved to be fundamental for the reproducibility of results.The apparent dry matter digestibility of diets for rabbits was measured in vivo (ADMDvv) and in vitro with the Ankom DaisyII Incubator. Four diets were tested: low fiber (LF), LF + 5% of pregerminated fenugreek seeds (PGFS) (LF5), LF + 10% PGFS (LF10), and high fiber (HF). For the ADMDvv, feces samples were collected from 56 White New-Zealand × Californian rabbits fed the 4 diets; animals were randomly allocated into 4 groups and housed in individual cages. For the in vitro trial, 3 methods were tested: fecal inoculum (FA) with Kansans State buffer; fecal inoculum with artificial saliva (FB); and multienzyme (ENZ). Fecal inocula were collected at slaughtering from the distal colon of rabbits fed ad libitum the LF diet. For FA and FB methods, the digestibility was measured at 36 and 48 h. The in vitro methods ranked the apparent dry matter digestibility of diets in the same order as in vivo, but ENZ values were always higher than FA and FB at 36 and 48 h. The prediction equations of in vivo digestibility with the ENZ method showed higher coefficient of determination (R2 = 0.69) and lower SE (0.190) than FA and FB; also, reproducibility was higher with ENZ (CV = 3.1%). In conclusion, different methods can be applied to the Ankom DaisyII Incubator to study the digestibility in rabbits. In our trial, the better reproducibility was observed with the multienzyme method than FA and FB were probably related to the variability of inocula.

EFFECTS OF SEX AND GENOTYPE ON MORPHOMETRIC TRAITS OF RABBIT

A total of one hundred (100) matured rabbit of 4 – 6 month of age comprising of New Zealand White (NZW) and Dutch (DUT) breeds were used in the study. They comprised of forty nine (49) New Zealand White, thirteen (13) males and thirty six (36) females, Fifty one (51) Dutch breed comprising of twenty one (21) males and thirty (30) females. The experiment was conducted at the Livestock Teaching and Research Farm, University of Maiduguri, Borno State. Maiduguri. The management system used was intensive system and semi intensive system. By housing them in a cage based on breed and sex. Each rabbit is housed in a cage measuring 33cm x 38cm x 45cm and the cages were tagged for easy identification, measurement and weighing. The cages were slightly raised above the ground for cross ventilation and to facilitate cleaning.Body weight was measured with a digital weighing scale in kilograms and the body measurements were measured using tailor tape calibrated in centimeters. The data measured are body weight (BW), body length (BL), nose to shoulder length (NSL), heart girth (HG), height at withers (HW), ear length (EL), leg length (LL), tail length (TL) and height of the rabbit (HR). Results obtained showed that sex had no significant effect on all the morphometric data measured. Significant effect of genotypes on morphometric traits were observed on NSL, HG, HW, EL and TL with their corresponding values of 10.83, 13.57, 13.37, 14.73, 10.95 in Dutch breed and corresponding values in

What is the restorative effect of VEGF inhibitor bevacuzimab against subarachnoid hemorrhage in an experimental model?

This study investigated the effect of vascular endothelial growth factor (VEGF) inhibitor bevacuzimab (BVZ) on the rabbit basilar artery using an experimental subarachnoid hemorrhage (SAH) model. Eighteen adult male New-Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH+BVZ group (n = 6). Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 10 mg/kg, intravenous BVZ for 2 days after the SAH. Basilar artery diameters were measured with magnetic resonance angiography (MRA) 72 h after the SAH in all groups. After 72 h, whole brains, including the upper cervical region, were obtained from all the animals after perfusion and fixation of the animal. The wall thickness, luminal area, and the apoptosis at the basilar arteries were evaluated in all groups. BVZ significantly prevented SAH-induced vasospasm confirmed in vivo with MRA imaging with additional suppression of apoptosis on basilar artery wall. VEGF inhibition with BVZ has shown to have a vasospasm and apoptosis attenuating effect on basilar artery in a SAH model.

Synthesis of 111In-p-SCN-Bn-DTPA-nimotuzumab and its preclinical evaluation in EGFR positive NSCLC animal model

Abstract The aim of this study was to investigate labeling of nimotuzumab (h-R3) with 111In using p-SCN-Bn-DTPA as bifunctional chelate, evaluate its targeting potential against SK-LU-1, H226, H650, H661, and HCC4006 non-small cell lung carcinoma (NSCLC) cell lines and correlate epidermal growth factor receptor (EGFR) expression level with internalization kinetics, biodistribution and imaging accuracy using Balb/c mice and New Zealand White rabbit (NZWR) animal model. The amount of p-SCN-Bn-DTPA attached to h-R3 was assessed by measuring relative absorbance at 652 nm with ultraviolet (UV) spectrophotometer. High-performance liquid chromatography (HPLC) was used to determine percent radiochemical purity (%RCP) and in vitro stability using excess amount of diethylenetriamine pentaacetate (DTPA). The in vitro stability in rat serum was estimated using iTLC-SG. EGFR expression level in each tumor was assessed by chemiluminescence. In vivo uptake in different organs of Balb/c mice and non-invasive imaging potential using NZWR bearing HCC4006 tumor, was evaluated with gamma camera. UV spectroscopy has confirmed the attachment of five p-SCN-Bn-DTPA (chelate) with one antibody. The HPLC indicated 98.85 ± 0.14% (n = 3) %RCP with high yield (&gt;96%), specific activity 3.5 ± 0.0.25 mCi per mg and 94.25 ± 0.34% in vitro stability at 37 °C in mice serum. In excess DTPA no considerable transchelation was experiential from the 111In labeled p-SCN-Bn-DTPA-h-R3 to the challenger. The EGFR expression in HCC4006 was higher amongst all with band density of 23.53 relative to 1.00 of H226. Initially internalization was lower which went up 1.05 × 104 molecules per HCC4006 cell in 48 h. The optimal concentration of h-R3 for maximum uptake was 15 μg per animal. Higher uptake in target organ was observed in animal infected with HCC4006 cells. However, in excess pure h-R3 the uptake was significantly reduced indicating tumor specificity. HCC4006 target site was undistinguishable relative to background activity in the initial phase of imaging due to poor uptake. However, within 60 h the HCC4006 tumor was quite apparent. This experiment suggests that at optimal dosage of 111In labeled h-R3 can be used for localization and identification of EGFR positive NSCLC using gamma camera.

Enhancement of Binding Affinity of Anti-Hapten Polyclonal IgG Recognizing Mitragynine using Affinity Purification

Antibodies are glycoproteins found in peritoneal fluid, serum, and blood. The antibody-based assay has been used for broad applications such as immunodiagnostic and other biomedical applications. Depending on the intended application, a highly purified polyclonal antibody could be used as an alternative. Purification of antibodies from anti-sera has been proven as one of the methods to enhance the binding affinity of antibodies towards its antigen. We report herein the enhancement of the binding affinity of anti-hapten polyclonal IgG recognizing mitragynine using affinity purification. Serum from the terminal bleed of New Zealand White (NZW) rabbits immunized with mitragynine conjugated with cationized– bovine serum albumin at methyl ester (C22-MG-cBSA), or aromatic ether modification (C9-MG-cBSA) were subjected to HiTrap Protein G affinity purification using fast protein liquid chromatography (FPLC). The elution peak from chromatography fractions was analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. Here, we report the binding of polyclonal antibodies produced from inoculation of either C22-MG-cBSA or C9-MG-cBSA immunogens of which mitragynine-ovalbumin (MG-OVA) was used as coating antigen in the ELISA assay. Non purified anti-sera from C22-MG-cBSA-inoculated rabbits showed higher titer than C9-MG-cBSA at 1/128 000 and 1/32 000 dilutions, respectively. The affinity of purified poly-IgGs from rabbits immunized with C22-MG-cBSA showed a mean Kd value of 7.965 × 10-6 μM, which was lower than those immunized with C9-MG-cBSA at mean Kd of 1.390 × 10-4 μM. In addition, the purified poly- IgGs showed higher binding towards MG-OVA than non-purified anti-sera at comparable protein concentrations. These results indicated that the higher binding affinity of purified polyclonal IgG is due to the reduced competition among polyclonal antibodies with non- IgG proteins that co-existed in the non-purified anti-sera after the affinity purification.

Early impairment of cartilage poroelastic properties in an animal model of ACL tear

BackgroundIn more than 50% of cases, anterior cruciate ligament (ACL) lesions lead to post-traumatic osteoarthritis. Ligament reconstruction stabilizes the joint, but the tear seems to impair the poroelasticity of the cartilage: synovial membrane fluid inflammation is observed 3 weeks after tearing. There have been some descriptions of visible cartilage changes, but poroelasticity has never been analyzed at this early stage. The present animal study aimed to determine (1) whether cartilage showed early poroelastic deterioration after ACL tear; (2) whether an impairment correlated with macroscopic changes; and (3) whether cartilage poroelasticity deteriorated over time. HypothesisIn the days following trauma, cartilage poroelasticity is greatly impaired, without macroscopically visible change. Material and methodsACL tear was surgically induced in 18 New-Zealand rabbits. Cartilage poroelasticity was assessed on indentation-relaxation test in 3 groups: “early”, at 2 weeks postoperatively (n=6), “mid-early” at 6 weeks (n=6) and in a non-operated control group (“non-op”). Macroscopic changes were scored in the same groups. ResultsPoroelastic impairment was greatest at the early time-point (2 weeks). Permeability ranged from a mean 0.08±0.05×10−15 m4/Ns (range, 0.028–0.17) in the “non-op” group to 1.03±0.60×10−15 m4/Ns (range, 0.24–2.15) in the “early” group (p=0.007). Shear modulus ranged from 0.53±0.11MPa (range, 0.36–0.66) to 0.23±0.10MPa (range, 0.12–0.43), respectively (p=0.013). Macroscopic deterioration, on the other hand, differed significantly only between the “mid-early” and the “non-op” groups: p=0.011 for cartilage deterioration and p=0.008 for osteophyte formation. At the “mid-early” time point, poroelastic deterioration was less marked, with 0.33±0.33×10−15 m4/Ns permeability (range, 0.06–1.06) and shear modulus 0.30±0.10MPa (range, 0.13–0.41: respectively p=0.039 and p=0.023 compared to the “non-op” group. DiscussionThe severe rapid deterioration in poroelasticity following ACL tear in an animal model, as notably seen in increased permeability, corresponds to changes in cartilage microstructure, with easier outflows of interstitial fluid. This mechanical degradation may underlie onset of microcracks within the cartilage, leading to physiological loading that the cartilage by its nature is unable to repair. Further investigations are needed to correlate these experimental data with clinical findings. Level of evidenceIII; comparative study with control group.

Effect of source and concentration of zinc on growth performance, meat quality and mineral retention in New Zealand rabbits

&lt;p&gt;Zinc supplementation in rabbit diet favours deposition of this mineral in meat and, therefore, contributes to satisfying the daily requirements of Zn in humans that consume it. A trial was conducted to study the effect of two sources (ZnSO&lt;sub&gt;4&lt;/sub&gt; and Zn-methionate) and two concentrations of Zn, along with a control (without Zn supplementation), on weight gain, meat quality and muscle retention in New Zealand White (NZW) rabbits during fattening stage. Treatments were randomly assigned to 100 NZW rabbits 40 days old, in a completely randomised experimental design using a factorial arrangement of treatments (2×2+control). The experimental period was 30 d. In each experimental treatment, weight gain, feed consumption and meat quality were recorded, as well as the retention of Zn in serum, liver, loin and hind leg. Results showed no differences (&lt;em&gt;P&lt;/em&gt;&amp;gt;0.05) in weight gain and food consumption, which can be attributed to diet-added Zn sources (ZnSO&lt;sub&gt;4&lt;/sub&gt; and Zn-methionate). Food conversion was better with the organic source at the highest concentration (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). Regarding meat quality, no differences were found (&lt;em&gt;P&lt;/em&gt;&amp;gt;0.05) in hind legs for source effect and Zn concentration, while in loin, differences (&lt;em&gt;P&lt;/em&gt;=0.02) were found in the colour parameter of L* and B* when the organic source of Zn (Zn-methionate) was supplied. Most retention of Zn on the loin occurred when a concentration of 25 mg Zn kg&lt;sup&gt;–1&lt;/sup&gt; of Zn-methionate was added, which could be important to provide larger amounts of Zn for human consumption.&lt;/p&gt;

Impact of Saccharomyces Cerevisiae Boulardii Supplementation As Probiotic On Productive Performance And Economic Efficiency Of Growing Rabbits

Our study was carried out at the farm of Faculty of Agriculture, Ain Shams University, Egypt. The average temperatures were 18.4°C and 23.9 °C from December 2017 - February 2018 to study the effects of Saccharomycescerevisiaeboulardii supplementation (as feed additives) on productive performance of growing rabbits. Sixty growing rabbits of the NZW (New Zealand White Rabbits), (4 weeks old) and weighted (603.62 gm mean body weight) were randomly distributed into 4 treated groups, n=15 rabbits per each group. Rabbits of supplemented groups were given 100 (R1), 200 (R2) and 400 (R3) gm/ton feed of Saccharomyces cerevisiaeboulardii mixed in the diet for 6 successive weeks. Individual live body weight was noted weekly from start till the end of the experiment. At the end of the experimental period, 10 rabbits (from each group) were fasting for 12 hrs, then slaughtered for carcass traits measure. Experimental lighting system was 16-hours photoperiod /day (16L: 8D) through both daily natural and the artificial fluorescent lighting. A pelleted ration of 17.3% crude protein, 13.37% crude fiber and 2510 kcal of digestible energy per kg feed was offered ad libitum all the time. Results revealed significant (P≤0.05) increases in the final body weight and daily weight gain with saccharomyces cerevisiae supplementation when compared with control group. Though, significantly (P≤0.05) improved feed conversion ratio in all treated groups compared with control one were noticed. Feed intake was the lower in treated groups than control group. There were significant (P≤0.05) increasing in hot carcass weight and carcass percentage with respect to the control group. Supplemented Saccharomycescerevisiae reduced (P≤0.05) the liver, heart, lungs and kidneys percentages compared the control group. Supplemented rabbit feeds with saccharomycescerevisiaeboulardii in their diets had highly increasing in relative economic efficiency and clear improvement of net revenue than control group.

Drug Release and Pharmacokinetic Evaluation of Novel Implantable Mometasone Furoate Matrices in Rabbit Maxillary Sinuses.

Intranasal corticosteroid sprays (INCSs) used to treat chronic rhinosinusitis are suboptimal due to limited penetration into the middle meatus, rapid clearance, and poor patient compliance. A bioresorbable drug matrix, developed with the XTreoTM drug delivery platform, may overcome the limitations of INCS by providing continuous dosing over several months. To evaluate the in vitro drug release and in vivo pharmacokinetics of novel mometasone furoate (MF) matrices in a rabbit dorsal maxillary osteotomy model. XTreoTM matrices were formulated to consistently elute MF for up to 6 months. Matrices were surgically placed bilaterally into the maxillary sinuses of New Zealand White (NZW) rabbits. Tissue and plasma MF concentrations were measured to assess the in vivo drug delivery. The in vivo and in vitro drug release kinetics of the matrices were quantified and compared to those of rabbits receiving daily Nasonex® MF nasal sprays. XTreoTM matrices self-expanded upon deployment to conform to the irregular geometry of the maxillary sinus cavities in the NZW rabbits. Sustained release of MF was demonstrated in vitro and in vivo for 2 MF matrices of distinct release durations and an in vitro-in vivo correlation was established. Therapeutic levels of MF in local tissues were measured throughout the intended dosing durations. In contrast to the variable peaks and troughs of daily nasal sprays, sustained dosing via a single administration of MF matrices was confirmed by quantifiable plasma MF concentrations over the intended dosing duration. The XTreoTM MF matrices provided targeted and efficient dosing to local sinus tissues that was superior to INCS. Sustained drug release was confirmed both in vitro and in vivo. The novel XTreoTM technology may provide precisely tuned, long-lasting drug delivery to sinus tissues with a single treatment.