New Zealand White Research Articles

Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits.

Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.

Matcha Green Tea Powder does not Prevent Diet-Induced Arteriosclerosis in New Zealand White Rabbits Due to Impaired Reverse Cholesterol Transport.

Green tea is associated with decreased risk for cardiovascular disease and stroke. Matcha is a special kind of powdered green tea known for its use in the Japanese tea ceremony. Due to its influence on lipoprotein parameters, it has been postulated to exert antiatherogenic effects. This study investigates whether it modulates the high-density lipoprotein (HDL) function and thereby influences the atherogenic process in an animal model with a strong influence on humans' situation. After a pretreatment phase based on a standard diet, 10 female New Zealand White (NZW) rabbits are fed a high-fat diet for 20 weeks. The treatment group is additionally administered 1% matcha during the whole experiment. Long-term matcha treatment leads to lowered HDL cholesterol, impaired cholesterol transport manifested by reduced in vitro cholesterol efflux capacity, reduced cholesteryl ester transfer protein (CETP)-mediated cholesterol ester (CE) transfer between HDL and triglyceride-rich particles, and reduced macrophage-specific in vivo transfer, where ian increased absorption of cholesterol in the liver but a decreased secretion into bile is observed. Pulse wave velocity, assessed by nuclear magnetic resonance, is increased in matcha-treated animals, and a similar trend is observed for atherosclerotic lesion formation. Long-term matcha green tea treatment of hypercholesterolemic rabbits cause impaired reverse cholesterol transport and increased vascular stiffness, and susceptibility for atherosclerotic lesion development.

Genetic Diversity of Rabbit (Oryctolagus cuniculus) Population in South Eastern Nigeria Using Microsatellite Markers

A study was conducted to estimate the diversity that exists among three rabbit populations adapted to the South-Eastern part of Nigeria. Blood samples were collected from 75 matured, mixed-sex, and unrelated three rabbit breeds selected across the zone. Eight microsatellites (Sol30, Sol33, and Sol44, Sat3, Sat7, Sat8, Sat12, and INRA) markers were used for the study. These microsatellites were uniformly distributed among rabbit genomes for genotyping. Subsequently, genetic variability within and between breeds was calculated. Allelic frequencies and Hardy-Weinberg equilibriums as well as Analysis of Molecular Variance, were also estimated using GenAlEX 6.41 software. Discriminant Analysis of Principal Components (DAPC) for the population structure of the rabbit breeds was performed in R v.3.5.0 using the R package adegenet. All the 8 loci amplified in this study were found to be 100% polymorphic, the observed allele sizes and their frequencies for the microsatellite markers in every three breeds showed that the highest frequency was 0.330 for the allele with the size of 470bp at Sol33 locus in New Zealand White (NZW) rabbits. The Nei’s genetic identities and distances between Chinchilla (CHI) and Dutch (DUT), CHI and NZW, DUT and NZW obtained in this study were [0.173, 0.185, and 0.189] and [1.753, 1.689, and 1.666] respectively. The dendrogram and biplot revealed that the three breeds were identified at two separate clusters. In addition, the admixture level of an individual rabbit among the three breeds indicated that the breeds were not pure and also the existence of more polymorphism within the breed than among the breed diversity.

Repair of long bone defects of large size using a tissue-engineered periosteum in a rabbit model

Tissue engineering is a promising approach for bone regeneration. In this study, we aimed to investigate whether tissue engineered periosteum (TEP), which was fabricated by combining osteogenically-induced mesenchymal stem cells (MSCs) with porcine small intestinal submucosa (SIS), could restore long bone defects of large size in rabbits. Twenty-four adult New Zealand white rabbits (NZWRs) were used in the experiments. Long bone defects of large size (30 mm-50 mm; average, 40 mm) were established on both sides of NZWRs’ radii. The defects were treated with TEP (Group A), allogeneic deproteinized bone (DPB, Group B), TEP combined with DPB (Group C), and pure SIS (Group D). The healing outcome was evaluated by radiography and histological examination at 4, 8, and 12 weeks post-treatment. The radiographical findings showed that bone defects of large size were all repaired in Groups A, B and C within 12 weeks, whereas Group D (pure SIS group) failed to result in defect healing at 4, 8, and 12 weeks. Although there was some new bone regeneration connecting the allografts and bone ends, as observed under radiographical and histological observations, bone defects of large sizes were restored primarily by structurally allografted DPB within 12 weeks. The TEP groups (Groups A and C) showed partial or total bone regeneration upon histological inspection. Based on 12-week histological examinations, significantly more bone was formed in Group A than Group C (P < 0.05), and both groups formed significantly more bone than in Groups B and D. The results indicated that long bone defects of a large size could be restored by TEP or TEP combined with the DPB scaffold, and such materials provide an alternative approach to resolving pathological bone defects in clinical settings.

B-PO05-014 A RETROSPECTIVE STUDY OF SEASONAL VARIABILITY OF CARDIAC ELECTROPHYSIOLOGY IN THE RABBIT HEART

Rabbits are an important animal model for the study of cardiac electrophysiology and are suitable for analyzing mechanisms of cardiac arrhythmias. Rabbits are known to have seasonal variation in activity, behavior, and breeding; however, there are few data related to seasonal variation in electrophysiological parameters in the rabbit heart. To determine if there is significant seasonal variation in cardiac electrophysiology of the New Zealand White (NZW) rabbit heart. Male NZW rabbit hearts (N = 55) were purchased from an approved vendor and housed on a 12:12 hr light:dark cycle. Hearts were Langendorff-perfused for simultaneous optical mapping of Vm and Ca2+ with voltage-sensitive (RH237) and calcium-sensitive (Rhod2-AM) indicators, respectively. Data were collected from 2012-2016 and retrospectively analyzed. We defined the seasons meteorologically: December-February as winter, March-May as spring, June-August as summer and September-November as autumn. All data were collected while pacing at a constant cycle length of 300 ms. Retrospective data revealed seasonal variability in the action potential duration (APD) and in the calcium transient duration (CaTD). For summer compared to spring and autumn, APD50 (121.1 ± 11 vs. 137 ± 19.8 and vs. 135.3 ± 11.3 ms, p < 0.01 for both) and APD80 (151.1 ± 11.7 vs. 166.4 ± 17.6 and vs. 163.5 ± 11.9 ms, p < 0.01 for both) were significantly shorter, but not different from winter. For summer compared to spring, CaTD50 (123.8 ± 5.5 vs. 137.7 ± 13.2 ms, p < 0.01) and CaTD80 (162.8 ± 6.1 vs. 178.4 ± 16.9 ms, p = 0.11) were shorter. There was not significance difference in Vm-Ca2+ coupling (i.e., CaTD - APD) between seasons. APD and CaTD are significantly shorter in the summer months of isolated rabbit hearts. These data may provide insight into seasonal patterns of arrhythmia in humans, but should also be considered with regard to experimental rigor and reproducibility.

Impacts of nano-emulsified vegetable oil on growth, hemato-biochemical markers, oxidative stress, and gut microbiota of New Zealand white and V-line rabbits

The present study aimed to examine the impact of magic oil® (a nano-emulsified vegetable oil) (NEVO) on growth and carcass traits, serum metabolites, and intestinal microbiota of New Zealand White (NZW) and V-line rabbits. A total of 450 rabbits of both breeds (male, five weeks old) with a 700 ± 19 g average live body weight was uniformly distributed into six groups (75 rabbits per each). Each group was subdivided into five replicates, each of 15 rabbits. Animals randomly allocated into a two × three completely factorial design (two breeds: NZW and V-line, and three treatments of NEVO: control (0.0), 0.5, and 1.0 ml of NEVO per liter of water, respectively). The findings of the present study revealed that V- line rabbits recorded a significant increase in the final body weight, final body weight gain, and total feed conversion ratio, along with carcass traits when compared to New Zealand White (NZW). Comapred with the control group, the final body weight, final body weight gain, and carcass traits of rabbits, orally supplemented with NEVO were significantly improved. At the same time, feed intake was not significantly improved. The effect of the NEVO supplement and its association with the breed (p < 0.001) have improved significantly the final body weight, final body weight gain, feed conversion ratio and carcass characteristics. A significant improvement in serum and tissue metabolites was observed with increasing NEVO levels. A remarkable increase in the serum total protein and globulin associated with a significant reduction (p < 0.001) in the serum total lipids and total cholesterol levels were also noticed with increasing NEVO levels. Total bacterial count, and the population of Escherichia coli and lactobacilli in the jejunum and colon were significantly (p < 0.001) lower in both rabbit breeds supplemented with NEVO than that of the control group. Based on these findings, supplementation of NEVO enhanced growth, antioxidant status and minimized pathogenic bacteria in rabbits.

Three Immunocompetent Small Animal Models That Do Not Support Zika Virus Infection.

Zika virus (ZIKV) is a mosquito-borne flavivirus that is primarily transmitted to humans through the bite of an infected mosquito. ZIKV causes disease in infected humans with added complications of Guillain-Barré syndrome and birth defects in infants born to mothers infected during pregnancy. There are several large immunocompetent animal models for ZIKV including non-human primates (NHPs). NHP models closely reflect human infection; however, due to sample size restrictions, investigations into the effects of transmission route and the impacts on disease dynamics have been understudied. Mice have been widely used for modeling ZIKV infection, yet there are few ZIKV-susceptible immunocompetent mouse models and none of these have been used to investigate sexual transmission. In an effort to identify a small immunocompetent animal model to characterize sexual transmission of ZIKV, we attempt experimental infection of multimammate mice, New Zealand white rabbits, and Hartley guinea pigs. The multimammate mouse is the natural reservoir of Lassa fever virus and has been identified to harbor other human pathogens. Likewise, while NZW rabbits are susceptible to West Nile virus, they have not yet been examined for their susceptibility to infection with ZIKV. Guinea pigs have been successfully used as models for ZIKV infection, but only in immunocompromised life stages (young or pregnant). Here, it was found that the multimammate mouse and New Zealand White (NZW) rabbits are not susceptible ZIKV infection as determined by a lack viral RNA in tissues and fluids collected. Sexually mature male Hartley guinea pigs were inoculated subcutaneously and by mosquito bite, but found to be refractory to ZIKV infection, contrary to findings of other studies in young and pregnant guinea pigs. Interestingly, here it is shown that adult male guinea pigs are not susceptible to ZIKV infection, even when infected by natural route (e.g., mosquito bite). Although a new small animal model for the sexual transmission for ZIKV was not established through this study, these findings provide information on outbred animal species that are not permissive to infection (NZW rabbits and multimammate mice) and new information surrounding limitations of a previously established animal model (guinea pigs).

Dexamethasone-Eluting Contact Lens for the Prevention of Postphotorefractive Keratectomy Scar in a New Zealand White Rabbit Model.

To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1% dexamethasone drops applied 4 times a day for 4 weeks.

Role of Hridayarnava Rasa on Inflammatory Responses in Rabbits with High Fat Diet Induced Atherosclerosis

Background: Atherosclerotic plaque formation is a chain of events that begins with fatty streak accumulation followed by monocytes infiltration and lipid core formation. Monocytes/macrophages play an important role in the initiation and progression of atherosclerosis. The role of inflammation and atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies in high-fat diet (HFD) induced atherosclerosis rabbits. Identifying triggers for inflammation and uncovering the details of inflammatory pathways may ultimately present new therapeutic targets. H. Rasa maintains the heart by providing cardioprotective activity along with changes in certain inflammatory markers in atherosclerosis. Objectives: The primary objective of the study is to evaluate the role of oxidized low-density lipoprotein cholesterol (LDLc) in the inflammatory response and how this inflammation triggers the level of white blood cells. The secondary objective is how this Hridayarnava Rasa, an Ayurvedic formulation inhibits the oxidation of LDLc and protects cells from inflammation in HFD-induced atherosclerosis model rabbits. Materials and Methods: Newzealand white rabbits of 24 were randomly divided into 6 groups of 4 animals each. Group I rabbits fed with standard pellet diet; group II rabbits fed with HFD; group III, IV, and V were fed with HFD and different doses of H. Rasa and group VI rabbits were fed with HFD plus Atorvastatin. Results: Total leucocytes, lymphocytes, monocytes, LDLc: high-density lipoprotein cholesterol (HDLc) ratio and total cholesterol (TC): HDLc ratio were increased in group II, III, IV, and VI of 30, 60, and 90 days when compared to group I. The levels of total leukocytes, lymphocytes, monocytes, LDLc: HDLc ratio, and TC: HDLc ratio were significantly reduced in group IV and V of 30, 60, and 90 days when compared to group II. In the present study, treatment with H. Rasa (group V) (i.e., 41.07 mg/kg. b. wt/p. o) was shown to be most effective over 90 days. Conclusion: These results suggest that HFD accelerates the development of atherosclerosis by increasing the inflammatory markers such as oxidized LDL (oxLDLc) and leukocyte counts in a time-dependent manner and H. Rasa protects the aorta by preventing the oxidative damage of LDLc which inturn maintains the inflammatory markers and provided the anti-inflammatory responses and protects the aorta from atherosclerotic plaque formation in a dose-and time-dependent manner. Limitation of the Study: This study focused on the characteristics of the rabbit lipoprotein pathway and pathophysiology of atherosclerotic lesions via inflammatory markers. This paper primarily determines how H. Rasa protects the aorta from the formation of atherosclerotic plaques caused by oxidative low-density lipoprotein. Further studies will need to focus specifically on the inflammatory pathways and the role of H. Rasa.

Effects of Hamo NK hard capsule on experimental atherosclerosis model

This study evaluated the effects of Hamo NK hard capsule on athresclerosis using experimental atherosclerosis model. NewZealand White rabbits were fed a high-fat diet (HFD) containing cholesterol and peanut oil. The animals received oral administration of HFD and Hamo NK hard capsule at two doses of 0.126 and 0.378 g/kg bw/day for 8 consecutive weeks. Blood samples were collected for analyis of biochemical parameters at before treatment, week 4 and week 8. Histopathology assessments of the aortic artery and liver were carried out at the end of the experiment. Hamo NK was effective in reducing serum triglyceride level after 8 weeks of the experiment. In addition, Hamo NK at two doses of 0.126 g/kg b.w and 0.378 g/kg b.w for 8 consecutive weeks did not affect the cholesterol, LDL-C and HDL-C concentrations induced by a HFD. Hamo NK at the dose of 0.126 g/kg bw/day was not only able to decrease significant aortic surface lesions but also capable of managing atherosclerosis plaques formation in aorta; whereas theses activities were not notiaceable at the dose of 0.378 g/kg b.w.

Calcium fructoborate coating of titanium-hydroxyapatite implants by chemisorption deposition improves implant osseointegration in the femur of New Zealand White rabbit experimental model.

Background: The identification of biocomposites that improve cell adhesion and reduce bone integration time is a great challenge for implantology and bone reconstruction. Aim: Our aim was to evaluate a new method of chemisorption deposition (CD) for improving the biointegration of hydroxyapatite-coated titanium (HApTi) implants. CD method was used to prepare a calcium fructoborate (CaFb) coating on a HApTi (HApTiCaFb) implant followed by evaluation of histological features related to bone healing at the interface of a bioceramic material in an animal model. Methods: The coating composition was investigated by high-performance thin-layer chromatography/mass spectrometry. The surface morphology of the coating was studied by scanning electron microscopy (SEM), before and after the in vitro study. We implanted two types of bioceramic cylinders, HApTi and HApTiCaFb, in the femur of 10 New Zealand White (NZW) rabbits. Results: The release of CaFb from HApTiCaFb occurred rapidly within the first three days after phosphate-buffered saline immersion; there was then a linear release for up to 14 days. SEM analysis showed similar morphology and particle size diameter for both implants. Around the porous HApTiCaFb implant, fibrosis and inflammation were not highlighted. Conclusions: Easily applied using CD method, CaFb coatings promote HApTi implant osseointegration in the femur of NZW rabbits.

Effect of the Spatial Distribution of the Temperature and Humidity Index in a New Zealand White Rabbit House on Respiratory Frequency and Ear Surface Temperature.

Simple SummaryA rabbit house’s microclimate has a strong influence on the physiological responses of rabbits, and thermal discomfort may damage their development. The primary aim of this study was to develop a spatial distribution of temperature and humidity index (THI) maps via kriging interpolation, as well as to characterize and evaluate its relationship with physiological responses (i.e., the respiratory frequency (RF) and ear surface temperature (EST) of New Zealand white (NZW) rabbits kept in a rabbit house. The spatial distribution maps of THI allowed us to visualize the heterogeneity in the distribution space of the variables, as well as to identify regions where NZW rabbits were exposed to unfavorable developmental conditions. The relationship between THI, RF, and EST was evident, and the maps showed that an increase in THI led to an acceleration of respiratory movements and an elevation of surface temperature in rabbit ears. This led to an attempt to dissipate excess heat acquired from the environment. Thus, the spatial distribution maps of THI overlaid with RF and EST data was found to provide useful information to assist the producer in making decisions to improve the production environment for NZW rabbits.The objective of this study was to characterize and evaluate the temperature and humidity index (THI) of New Zealand white (NZW) rabbits kept in a rabbit house using geostatistical techniques. Furthermore, we sought to evaluate its relationship with respiratory frequency (RF) and ear surface temperature (EST). The experiment was conducted at the Federal University of Lavras, Brazil. A total of 52 NZW rabbits were used. For the characterization of the thermal environment, the dry bulb temperature (tdb, °C), relative humidity (RH, %), and dew point temperature (tdp, °C) were collected at 48 points in the rabbit house at 6:00 a.m., 12:00 p.m., and 6:00 p.m. for seven days. The RF and EST of the animals was monitored. Subsequently, the THI was calculated and the data were analyzed using geostatistical tools and kriging interpolation. In addition, the RF and EST data were superimposed on the rabbit house’s THI data maps. The magnitude of the variability and structure of the THI inside the rabbit house were characterized and the heterogeneity was visualized. Critical THI points inside the rabbit house and in locations where animals with high RF and ESTs were housed were identified, thus providing information about improving the production environment.

PRODUCTIVE PERFORMANCE AND PHYSOLIGICAL RESPONSE OF GROWING RABBITS AS AFFECTED BY USING SUGAR BEET PULP WITH OR WITHOUT ENZYMES MIXTURE SUPPLEMENT

This study evaluated the effect of using two dietary levels (20 or 40% of the diet) sugar beet pulp (SBP) with or without enzymes mixture supplement (Smizyme) at a level of 0.3g/kg diet on growth performance, nutrients digestibility, some blood parameters, immune response, antioxidant activity and economic profit of growing rabbits. Seventy five weaned New Zealand White (NZW) rabbits, six weeks old, with an average live body weight 729.52± 18.97g were randomly divided into five groups (fifteen rabbits, each). Rabbits were fed on 5 experimental diets as follows: diet 1: A control without SBP,2, 3fed diets 20 and 40%SBPwithout enzymes mixture and 4, 5 fed diets 20 and 40%S BP with enzymes mixture .The growth trail lasted about 8 weeks The results indicated that, inclusion of 40% SBP with enzymes mixture in rabbit diet significantly increased final body weight, daily body weight gain, improve feed conversion, relative growth rate and performance index, dressing% and also gave the highest economical efficiency than those fed control diet. Digestibility coefficients of DM, CP, EE, NFE significantly increased with replacement 20 or 40% SBP with enzymes mixture in rabbit diets. Feeding on40% SBP with enzymes mixture increased significantly digestibility coefficients of OM and CF as compared to rabbits fed control diet. Albumin/ Globulin ratio, AST and Catalase were significantly increased with replacement 20 or 40% SBP with enzymes mixture in rabbit diets compared to control. However, total cholesterol and Malondialdehyde significantly decreased with replacement 40% SBP with enzymes mixture in rabbit diet as compared with control diet. Feeding rabbits on 40% SBP with enzymes mixture achieved significantly higher IgG and IgM than those fed control diet. Conclusively, it could be recommended replacement sugar beet pulp SBP up 40% with enzymes mixture of the rabbit diets to improve the performance, antioxidant status, immunity functions and economic return of the growing rabbits.

Rabbit as an animal model for the study of biological grafts in pelvic floor dysfunctions

The aims of this study were to evaluate the feasibility of the New Zealand White (NZW) rabbit for studying implanted biomaterials in pelvic reconstructive surgery; and to compare the occurrence of graft-related complications of a commercial polypropylene (PP) mesh and new developed human dermal matrix implanted at vaginal and abdominal level. 20 white female NZW rabbits were randomized into two groups, experimental group (human acellular dermal matrices-hADM-graft) and control group (commercial PP graft). In each animal, grafts were surgically implanted subcutaneously in the abdominal wall and in the vaginal submucosa layer for 180 days. The graft segments were then removed and the surgical and clinical results were analyzed. The main surgical challenges during graft implantation were: (a) an adequate vaginal exposure while maintaining the integrity of the vaginal mucosa layer; (b) to keep aseptic conditions; (c) to locate and dissect the breast vein abdominal surgery; and (d) to withdraw blood samples from the ear artery. The most abnormal findings during the explant surgery were found in the PP group (33% of vaginal mesh extrusion) in comparison with the hADM group (0% of vaginal graft extrusion), p = 0.015. Interestingly, macroscopic observation showed that the integration of the vaginal grafts was more common in the hADM group (40%) than in the PP group, in which the vaginal mesh was identified in 100% of the animals (p = 0.014). The NZW rabbit is a good model for assessing materials to be used as grafts for pelvic reconstructive surgery and vaginal surgery. Animals are easily managed during the procedures, including surgical intervention and vaginal mucosa approach. Additionally, hADM is associated with fewer clinical complications, as well as better macroscopic tissue integration, compared to PP mesh.

Oral administration of Moringa oleifera leaf powder relieves oxidative stress, modulates mucosal immune response and cecal microbiota after exposure to heat stress in New Zealand White rabbits

BackgroundHeat stress (HS) disrupts the gut barrier allowing the uptake of lipopolysaccharide (LPS) and leads to an inflammatory response and changes in gut microbiota composition. Moringa oleifera leaf powder (MOLP) has been proposed to combat HS, yet its alleviate role is currently under investigation. The current study investigated the effects of chronic HS and MOLP supplementation on changes in redox status and immune response of cecal mucosa along with alteration in cecal microbiota.MethodsA total of 21 young New Zealand White (NZW) rabbits (male) about 32 weeks old (mean body weight of 3318 ± 171 g) reared on a commercial pelleted diet were employed; divided into three groups (n = 7): control (CON, 25 °C), heat stress (HS, 35 °C for 7 h daily), and HS supplemented orally with MOLP (HSM, 35 °C) at 200 mg/kg body weight per day for 4 weeks.ResultsThe results demonstrated that MOLP supplementation increased organ index of cecal tissue compared with the HS group (P > 0.05). Levels of malonaldehyde (MDA) and activity of superoxide dismutase (SOD) as well as lactate dehydrogenase (LDH) were reduced in the cecal mucosa of the HSM group compared with the HS group. MOLP downregulated the contents of cecal mucosa LPS, several inflammatory markers (TNF-α/IL-1α/IL-1β), and myeloperoxidase (MPO) in the HSM group (P < 0.05). Secretory immunoglobulin A (SIgA) was increased in the HSM group compared with the HS group (P < 0.05). The transcriptome of cecal mucosa showed that MOLP reduced gene expression relative to several immune factors, including IL-10, IFNG, and RLA, whereas both HS and MOLP increased the gene expression of fat digestion and absorption pathway, including APOA1, FABP1, FABP2, MTTP, and LOC100344166, compared to the CON group (P < 0.001). At the phylum level, the relative abundance of Proteobacteria was increased by HS, while Actinobacteria was significantly increased by HSM compared to other groups (P < 0.05). At genus level, Papillibacter was higher in abundance in HSM groups compared to CON and HS groups (P < 0.05). Higher butyrate concentrations were observed in the HSM group than HS and CON groups (P < 0.05).ConclusionIn conclusion, HS in growing rabbits resulted in alteration of cecal microbiota at phyla level as well as increased oxidative stress and expression of mucosal inflammatory genes. Whereas, oral MOLP supplementation elevated the relative weight of cecum, affected their immunological and cecal micro-ecosystem function by improving antioxidant status and down-regulating mucosal tissue inflammatory response.

The impacts of treatment with newly developed probiotic versus phaleria macrocarpa leaves extract on the histological features in immunocompromised New Zealand white rabbits

This research aimed to examine the possible effectiveness of treatment with a freshly formulated new probiotic versus Phaleria macrocarpa leaves extract indicated by the histopathological changes occurred to the colon of the immunocompromised New Zealand White (NZW) rabbits. The study included 40 rabbits, divided into 4 groups. Three of the groups were fed with the immunosuppressive medication (azathioprine, 500 mg/kg/day) to be immunocompromised, Group B was treated with P. macrocarpa extract, Group Ctreated with our developed probiotic, and the group D left untreated as a positive control, Group A regarded as control negative. The duration of immunocompromising drug induction was set as 14 days; and the period of treatment was set for another 14 days. Distinctly, the treated rabbits were showing improvements of healing processes compared to non-treated, where the signs of lack of normal mucous folds, different degrees of mucosal edema and congestion, submucosal hemorrhage, accumulative score of gross colon morphology and major severe lesions of the colon tissue of the non-treated were significantly improved in the probiotic treated, as well as, P. macrocarpa treated groups. As a conclusion, the results indicated that uptake of the formulated probiotic could strengthen rabbits’ immune responses of the immunoco-mpromised rabbits significantly (both the specific and non-specific responses) and retain the weakened colon tissues (caused by the immunosuppressant drug). These findings are recommended to be used in future for development of promising commercial supplements to mitigate the medical risks that comes with immunosuppressant medications currently given to animals or human patients under certain circumstances.

Pharmacokinetics and Safety of an Intravitreal Humanized Anti-VEGF-A Monoclonal Antibody (PRO-169), a Biosimilar Candidate to Bevacizumab.

BackgroundPRO-169 is a biosimilar candidate to bevacizumab (BEV), a monoclonal antibody (mAb) that inhibits vascular endothelial growth factor-A (VEGF-A) developed for intravitreal use. The current study demonstrates the intraocular pharmacokinetics (PK) of PRO-169 and its safety using New Zealand white (NZW) rabbits.MethodsIntraocular concentration was evaluated in thirty-six rabbits at 1h, 1, 2, 5, 14 and 30 days after a single bilateral injection of PRO-169 or BEV (1.25 mg/0.05 mL). In a secondary experiment, safety was evaluated after three consecutive unilateral injections at 30-day intervals in twenty-four rabbits (PRO-169: 1.25 mg/0.05 mL or ranibizumab [RZB]: 0.5 mg/0.05 mL), by liver-associated enzymes (LAE), ophthalmological examination and adverse event (AE) incidence. Primary endpoints were vitreous maximum concentration (Cmax), time to attain maximum concentration (tmax), area under curve (AUC0-t), half-life (t1/2) and LAE. Secondary endpoints included aqueous humor (AH) and plasma pharmacokinetics, clinical examination and AEs.ResultsThe Cmax in the vitreous was 593.75 ± 45.63 (PRO-169) vs 644.79 ± 62.65 µg/mL (BEV) (p= 0.136). Tmax was 0.53 ± 0.82 vs 0.85 ± 0.73 days (p= 0.330). The AUC0-t was 3837.72 ± 465.91 vs 4247.31 ± 93.99 days*µg/mL (p= 0.052) and the half-life was 4.99 ± 0.89 vs 5.18 ± 0.88 days (p= 0.711). LAEs were normal in 92% of NZW rabbits; no differences between groups were observed (p>0.05). The AH and plasma PKs were also similar. Finally, clinical examinations found no alterations. AEs were observed in 25% of PRO-169 rabbits, without differences vs RZB (p=0.399).ConclusionPRO-169 can be efficiently diffused and distributed in ocular compartments, showing vitreous pharmacokinetics analogous to BEV. The safety experiment did not find evidence of clinical alterations from a repeated injection of PRO-169. These results provide scientific justification supporting that PRO-169 should be evaluated in future clinical trials to confirm its safety and efficacy.

Growth performance, tissue precipitation, metallothionein and cytokine transcript expression and economics in response to different dietary zinc sources in growing rabbits.

The impact of different dietary zinc sources on the growth, serum metabolites, tissue zinc content, economics and relative expression of cytokine and metallothionein genes was evaluated in this study. A total of 120 35-day-old male New Zealand White (NZW) rabbits were randomly distributed into four dietary experimental groups with 10 replicates per group and 3 animals per replicate. The control group was fed basal diet with a Zn-free vitamin-mineral premix; the other three groups received control basal diet supplemented with 50mg/kg level with zinc oxide (ZnO; as inorganic source), Zn-methionine (Zn-Met; as organic source) and zinc oxide nanoparticles (nano-ZnO). The results indicated that Zn-Met and nano-ZnO groups significantly improved body weight, daily weight gain (DWG), feed conversion ratio (FCR) and nutrient digestibility, as well as decreased mortality, compared to ZnO and control groups. Zn-Met and nano-ZnO significantly reduced serum total cholesterol but did not affect serum proteins and liver function. Nano-ZnO supplemented group also recorded the highest value of serum alkaline phosphatase (ALP), insulin-like growth factor (IGF-1) and lysozymes compared to other groups. Nano-ZnO supplementation had increased hepatic Zn and Cu content and decreased faecal Zn content. Also nano-ZnO group recorded higher expression levels of genes encoding for metallothionein I and metallothionein II, interleukin-2 and interferon-γ in the liver of rabbits. The findings of this study demonstrated zinc nanoparticles, and organic zinc supplementation had improved growth performance and health status of growing rabbits than inorganic zinc oxide.

Quality Characteristics Carcasses Of New Zealand White Crossbred Rabbit Was Given FOS (Fructooligosaccharide) From Ambon Banana Peel Isolation

Fructooligosaccharide (FOS) is an alternative solution to control colibacillosis which can eliminate pathogenic bacteria in the contamination tract and stimulate the immune system (immunostimulants). The fructan contained in FOS produced by hydrolysis of chicory plant inulin has been widely reported, but the production of FOS from banana peel waste has not been widely published. This research aims to know and study the carcass characteristics of New Zealand White (NZW) crossbred rabbits given FOS (Fructooligosaccharide) from Ambon Banana Peel. The material used in this study were 42 New Zealand White crossbred rabbits 2 months old with 3 replications with 7 treatments, the percentage of FOS was 0%, 2.5%, 5%, 7.5%, 10%, 12.5%, and 15%, which is given through drinking water after 2 weeks of maintenance for 7 consecutive days at 08.00 am. The conclusion of this study that the provision of FOS (Fructooligosaccharide) from banana peel isolation had a significant effect on the carcass characteristics of New Zealand White crossbred rabbits (P &lt;0.05) on carcass weight, meat weight, bone percentage, and had a very significant effect (P &lt;0.01) on carcass percentage.

Long-term multimodal imaging characterization of persistent retinal neovascularization using DL-alpha-aminoadipic acid in pigmented and white rabbits

PurposeIntravitreal (IVT) injection of DL-alpha-aminoadipic acid (AAA) is a new animal model for retinal neovascularization (RNV) reported in rabbits. This study performs longitudinal multimodal imaging for up to 1 year to evaluate DL-AAA RNV in both New Zealand white (NZW) rabbits and Dutch-Belted pigmented (DBP) rabbits. MethodDetailed characterization and quantification of this model were performed in these two strains in 32 eyes by optical coherence tomography (OCT), fundus photography, and fluorescein angiography (FA) for up to 16 weeks following DL-AAA administration in 32 eyes and up to 52 weeks in 5 eyes. H & E histology was also performed in these two strains 8 weeks after injection of DL-AAA. ResultRNV was successfully generated using 50 μL 80 mM DL-AAA solution for DBP rabbits and 80 μL 80 mM DL-AAA for NZW rabbits. The incidence of persistent vascular leakage is 100% (15/15) for DBP rabbits and 70.6% (12/17) for NZW rabbits at 16 weeks. Complications with NZW rabbits ultimately decreased the efficiency in NZW rabbits to 58.8% (10/17) of NZW rabbits getting persistent (to 16 weeks) vascular leakage without ocular complications as compared with 100% (15/15) in DBP rabbits. Five eyes (2 DBP and 3 NZW) were selected from those demonstrating RNV at 16 weeks and were monitored for up to 52 weeks. All 5 demonstrated persistent RNV to 52 weeks. Quantification of the mean leakage area (MLA) in DBP rabbits is more accurate than in NZW rabbits since the reduced contrast between the leakage and background in NZW rabbits makes it more challenging to quantify. ConclusionDL-AAA can induce persistent and quantifiable RNV in both DBP and NZW rabbits. DBP rabbits have a higher success rate, lower required volume of DL-AAA, and more accurate method for quantification that could be more desirable.