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1.
Cells ; 13(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38727293

ABSTRACT

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.


Subject(s)
Cell Differentiation , Chondrocytes , Chondrogenesis , Mesenchymal Stem Cells , Animals , Rabbits , Mesenchymal Stem Cells/metabolism , Chondrogenesis/genetics , Chondrocytes/metabolism , Receptors, Cytokine/metabolism , Receptors, Cytokine/genetics , Femur/pathology , Signal Transduction , Cell Line , Mesenchymal Stem Cell Transplantation
2.
Sci Rep ; 14(1): 10618, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724594

ABSTRACT

Various kinds of pets have been known to contract the ectoparasite Sarcoptes scabiei. Current acaricides are becoming less effective because of the resistance developed by the mite besides their adverse effects on the general activity and reproductive performance of domestic pets. For this reason, the present study aims to discover a novel and safe approach using silver and gold nanoparticles to fight Sarcoptic mange in rabbits as well as to explain their mechanism of action. 15 pet rabbits with clinical signs of Sarcoptic mange that were confirmed by the microscopic examination were used in our study. All rabbits used in this study were assessed positive for the presence of different developing stages of S. scabiei. Three groups of rabbits (n = 5) were used as follows: group (1) didn't receive any treatment, and group (2 and 3) was treated with either AgNPs or GNPs, respectively. Both nanoparticles were applied daily on the affected skin areas via a dressing and injected subcutaneously once a week for 2 weeks at a dose of 0.5 mg/kg bwt. Our results revealed that all rabbits were severely infested and took a mean score = 3. The skin lesions in rabbits that didn't receive any treatments progressed extensively and took a mean score = of 4. On the other hand, all nanoparticle-treated groups displayed marked improvement in the skin lesion and took an average score of 0-1. All NPs treated groups showed remarkable improvement in the microscopic pictures along with mild iNOS, TNF-α, and Cox-2 expression. Both nanoparticles could downregulate the m-RNA levels of IL-6 and IFγ and upregulate IL-10 and TGF-1ß genes to promote skin healing. Dressing rabbits with both NPs didn't affect either liver and kidney biomarkers or serum Ig levels indicating their safety. Our residual analysis detected AgNPs in the liver of rabbits but did not detect any residues of GNPs in such organs. We recommend using GNPs as an alternative acaricide to fight rabbit mange.


Subject(s)
Gold , Metal Nanoparticles , Sarcoptes scabiei , Scabies , Silver , Animals , Rabbits , Metal Nanoparticles/chemistry , Metal Nanoparticles/administration & dosage , Gold/chemistry , Scabies/drug therapy , Scabies/parasitology , Silver/chemistry , Sarcoptes scabiei/drug effects , Skin/drug effects , Skin/parasitology , Skin/pathology , Skin/metabolism
3.
BMC Genomics ; 25(1): 458, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730432

ABSTRACT

BACKGROUND: While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. RESULTS: The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy - Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the - 600 to - 1200 segment, in which the four SNPs were located. CONCLUSIONS: The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.


Subject(s)
Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Skin , Animals , Rabbits , Skin/metabolism , Phenotype , Hair Follicle/metabolism
4.
Int J Mol Sci ; 25(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731811

ABSTRACT

Recently studied N-(ß-d-glucopyranosyl)-3-aryl-1,2,4-triazole-5-carboxamides have proven to be low micromolar inhibitors of glycogen phosphorylase (GP), a validated target for the treatment of type 2 diabetes mellitus. Since in other settings, the bioisosteric replacement of the 1,2,4-triazole moiety with imidazole resulted in significantly more efficient GP inhibitors, in silico calculations using Glide molecular docking along with unbound state DFT calculations were performed on N-(ß-d-glucopyranosyl)-arylimidazole-carboxamides, revealing their potential for strong GP inhibition. The syntheses of the target compounds involved the formation of an amide bond between per-O-acetylated ß-d-glucopyranosylamine and the corresponding arylimidazole-carboxylic acids. Kinetics experiments on rabbit muscle GPb revealed low micromolar inhibitors, with the best inhibition constants (Kis) of ~3-4 µM obtained for 1- and 2-naphthyl-substituted N-(ß-d-glucopyranosyl)-imidazolecarboxamides, 2b-c. The predicted protein-ligand interactions responsible for the observed potencies are discussed and will facilitate the structure-based design of other inhibitors targeting this important therapeutic target. Meanwhile, the importance of the careful consideration of ligand tautomeric states in binding calculations is highlighted, with the usefulness of DFT calculations in this regard proposed.


Subject(s)
Enzyme Inhibitors , Glycogen Phosphorylase , Imidazoles , Molecular Docking Simulation , Kinetics , Rabbits , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Glycogen Phosphorylase/antagonists & inhibitors , Glycogen Phosphorylase/metabolism , Glycogen Phosphorylase/chemistry , Imidazoles/chemistry , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Computer Simulation , Structure-Activity Relationship , Triazoles/chemistry , Triazoles/pharmacology , Triazoles/chemical synthesis
5.
J Mass Spectrom ; 59(6): e5031, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38726684

ABSTRACT

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination. A Waters Symmetry C18 column was used to separate the analytes and internal standard. The composition of the mobile phase was like (A) 0.1% v/v formic acid in water and (B) methanol. The detection of MFX and AB was accomplished through the utilization of positive ion electrospray ionization under multiple reaction monitoring mode. The linearity curves for both analytes exhibited an acceptable trendline across a concentration range of 2.34-300 ng/mL for MFX and 7.81-1000 ng/mL for AB in surrogate rabbit tear fluid. The lower limit of quantitation for MFX was 2.34 ng/mL, while for AB, it was 7.81 ng/mL. The approach was strictly validated, encompassing tests of selectivity, linearity (with r2 > 0.99), precision, accuracy, matrix effects, and stability. Consequently, we employed this method to evaluate the pharmacokinetics profiles of MFX and AB in rabbit tear fluid following single topical doses.


Subject(s)
Moxifloxacin , Tandem Mass Spectrometry , Tears , Rabbits , Animals , Tandem Mass Spectrometry/methods , Tears/chemistry , Moxifloxacin/pharmacokinetics , Moxifloxacin/analysis , Reproducibility of Results , Amphotericin B/pharmacokinetics , Amphotericin B/analysis , Limit of Detection , Anti-Infective Agents/pharmacokinetics , Anti-Infective Agents/analysis , Chromatography, Liquid/methods , Ophthalmic Solutions/pharmacokinetics , Linear Models , Liquid Chromatography-Mass Spectrometry
6.
Int J Immunopathol Pharmacol ; 38: 3946320241249429, 2024.
Article in English | MEDLINE | ID: mdl-38721971

ABSTRACT

OBJECTIVE: This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by enhancing gastric residence time (GRT) and preventing gastro-esophageal reflux disease (GERD). METHOD: Various combinations of raft-forming agents, such as Tragacanth gum (TG), guar gum (GG), and xanthan gum (XG), were evaluated alongside sodium alginate (SA) to develop an effective raft. Preformulation studies and preliminary screening were conducted to identify the most suitable raft-forming agent, and GG was chosen due to its mucilaginous properties. The formulation was optimized using a 32 full factorial design, with the quantities of GG and SA as independent factors and apparent viscosity and in-vitro drug release (%) as dependent factors. The in vivo floating behavior study was performed for optimized and stabilized formulation. RESULTS: Among the tested batches, F6 was selected as the optimized formulation. It exhibited desirable characteristics such as adequate raft weight for extended floating in gastric fluid, improved apparent viscosity, and a significant percentage of drug release at 12 h. A mathematical model was applied to the in-vitro data to gain insights into the drug release mechanism of the formulation. The stability of the suspension was assessed under accelerated conditions, and it demonstrated satisfactory stability. The formulation remains floating in the Rabbit stomach for more than 12 h. CONCLUSION: It concludes that the developed formulation has enhanced bioavailability in the combination of GG and SA. The floating layer of the raft prevents acid reflux, and the famotidine is retained for an extended period of time in the gastric region, preventing excess acid secretion. The developed formulations are effective for stomach ulcers and GERD, with the effect of reducing acid secretion by H2 receptor antagonists.


Subject(s)
Drug Delivery Systems , Famotidine , Galactans , Famotidine/administration & dosage , Famotidine/pharmacokinetics , Animals , Drug Delivery Systems/methods , Drug Liberation , Alginates , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/metabolism , Biological Availability , Mannans/administration & dosage , Plant Gums , Viscosity , Male , Rabbits , Gastric Mucosa/metabolism , Gastric Mucosa/drug effects , Polysaccharides, Bacterial , Drug Stability , Administration, Oral
7.
J Exp Biol ; 227(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38699818

ABSTRACT

Little is known regarding the precise muscle, bone and joint actions resulting from individual and simultaneous muscle activation(s) of the lower limb. An in situ experimental approach is described herein to control the muscles of the rabbit lower hindlimb, including the medial and lateral gastrocnemius, soleus, plantaris and tibialis anterior. The muscles were stimulated using nerve-cuff electrodes placed around the innervating nerves of each muscle. Animals were fixed in a stereotactic frame with the ankle angle set at 90 deg. To demonstrate the efficacy of the experimental technique, isometric plantarflexion torque was measured at the 90 deg ankle joint angle at a stimulation frequency of 100, 60 and 30 Hz. Individual muscle torque and the torque produced during simultaneous activation of all plantarflexor muscles are presented for four animals. These results demonstrate that the experimental approach was reliable, with insignificant variation in torque between repeated contractions. The experimental approach described herein provides the potential for measuring a diverse array of muscle properties, which is important to improve our understanding of musculoskeletal biomechanics.


Subject(s)
Hindlimb , Muscle, Skeletal , Torque , Animals , Rabbits , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Hindlimb/physiology , Biomechanical Phenomena , Electric Stimulation , Male
8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(4): 289-295, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38710512

ABSTRACT

Objective To evaluate the toxicology of targeting human epidermal growth factor receptor-2 chimeric antigen receptor T (HER2-CAR-T) cells and to provide a safety basis for the clinical evaluation of HER2-CAR-T cell therapy. Methods The recombinant lentiviral vector was used to generate HER2-CAR-T cells. Soft agar colony formation assay was used to observe the colony formation of HER2-CAR-T cells, and the colony formation rate was statistically analyzed. The HER2-CAR-T cell suspension was co-incubated with rabbit red blood cell suspension, and the hemolysis of red blood cells was evaluated by direct observation and microplate reader detection. The HER2-CAR-T cell preparation was injected into the ear vein of male New Zealand rabbits, and the stimulating effect of HER2-CAR-T cells on the blood vessels of the animals was observed by staining of tissue sections. The vesicular stomatitis virus envelope glycoprotein (VSV-G) gene of pMD 2.G vector was used as the target sequence, and the safety of the lentiviral vector was verified by real-time fluorescence quantitative PCR. The heart, liver, lung, and kidney of mice receiving HER2-CAR-T cell infusion were collected, and the lesions were observed by HE staining. Results The HER2-CAR-T cells were successfully prepared. These cells did not exhibit soft agar colony formation ability in vitro, and the HER2-CAR-T cell preparation did not cause hemolysis in New Zealand rabbit red blood cells. After the infusion of HER2-CAR-T cells into the ear vein of New Zealand rabbits, no obvious vascular stimulation response was found, and no specific amplification of VSV-G was detected. No obvious lesions were found in the heart, liver, lung and kidney tissues of the treatment group. Conclusion The prepared HER2-CAR-T cells have reliable safety.


Subject(s)
Receptor, ErbB-2 , Receptors, Chimeric Antigen , Animals , Humans , Receptor, ErbB-2/genetics , Receptor, ErbB-2/immunology , Rabbits , Mice , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Male , Immunotherapy, Adoptive/methods , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Cell Line, Tumor , Genetic Vectors/genetics , Lentivirus/genetics , Female
9.
Jt Dis Relat Surg ; 35(2): 361-367, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38727116

ABSTRACT

OBJECTIVES: This study aims to compare the radiological, biomechanical, and histopathological results of microfracture treatment and osteochondral damage repair treatment with a new scaffold product produced by the three-dimensional (3D) bioprinting method containing gelatin-hyaluronic acid-alginate in rabbits with osteochondral damage. MATERIALS AND METHODS: A new 3D bioprinted scaffold consisting of gelatin, hyaluronic acid, and alginate designed by us was implanted into the osteochondral defect created in the femoral trochlea of 10 rabbits. By randomization, it was determined which side of 10 rabbits would be repaired with a 3D bioprinted scaffold, and microfracture treatment was applied to the other knees of the rabbits. After six months of follow-up, the rabbits were sacrificed. The results of both treatment groups were compared radiologically, biomechanically, and histopathologically. RESULTS: None of the rabbits experienced any complications. The magnetic resonance imaging evaluation showed that all osteochondral defect areas were integrated with healthy cartilage in both groups. There was no significant difference between the groups in the biomechanical load test (p=0.579). No statistically significant difference was detected in the histological examination using the modified Wakitani scores (p=0.731). CONCLUSION: Our study results showed that 3D bioprinted scaffolds exhibited comparable radiological, biomechanical, and histological properties to the conventional microfracture technique for osteochondral defect treatment.


Subject(s)
Alginates , Bioprinting , Cartilage, Articular , Gelatin , Hyaluronic Acid , Knee Joint , Printing, Three-Dimensional , Tissue Scaffolds , Animals , Rabbits , Alginates/chemistry , Gelatin/chemistry , Hyaluronic Acid/chemistry , Hyaluronic Acid/therapeutic use , Tissue Scaffolds/chemistry , Cartilage, Articular/pathology , Cartilage, Articular/injuries , Cartilage, Articular/surgery , Knee Joint/surgery , Knee Joint/pathology , Bioprinting/methods , Disease Models, Animal , Biomechanical Phenomena , Magnetic Resonance Imaging , Arthroplasty, Subchondral/methods
10.
Nat Commun ; 15(1): 3780, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710714

ABSTRACT

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.


Subject(s)
Choroidal Neovascularization , Dependovirus , Genetic Therapy , Genetic Vectors , Retinal Pigment Epithelium , Animals , Dependovirus/genetics , Genetic Vectors/genetics , Genetic Vectors/administration & dosage , Genetic Therapy/methods , Mice , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/virology , Choroidal Neovascularization/therapy , Choroidal Neovascularization/genetics , Rabbits , Humans , Gene Transfer Techniques , Macular Degeneration/therapy , Macular Degeneration/genetics , Macular Degeneration/pathology , Disease Models, Animal , Capsid Proteins/genetics , Capsid Proteins/metabolism , Transduction, Genetic , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Mice, Inbred C57BL , Retina/metabolism , Retina/virology , Male , HEK293 Cells
11.
Am J Reprod Immunol ; 91(5): e13853, 2024 May.
Article in English | MEDLINE | ID: mdl-38706383

ABSTRACT

BACKGROUND: The amniotic membrane (AM) has shown immense potential in repairing wounds due to its great regenerative qualities. Although the role of AM as a biological scaffold in repairing wounds has been studied well, the tissue regenerative potential of AM-derived mesenchymal stem cells (MSCs) and conditioned media (CM) derived from it remains to be discovered as of now. Here, we examined the wound healing abilities of fresh and frozen thawed rabbit AM (rAM) along with the MSCs and their lyophilised CM in rabbits challenged with skin wounds. METHODS: To elucidate the role of rAM-MSCs and its CM in repairing the wound, we isolated it from the freshly derived placenta and characterised their differentiation potential by performing an in vitro tri-lineage differentiation assay besides other standard confirmations. We compared the wound repair capacities of rAM-MSCs and lyophilised CM with the fresh and cryopreserved AM at different timelines by applying them to excision wounds created in rabbits. RESULTS: By monitoring wound contractions and tissue histology of wounded skin at different time points after the application, we observed that rAM-MSCs and rAM-MSC-derived CM significantly promoted wound closure compared to the control group. We also observed that the wound closure capacity of rAM-MSCs and rAM-MSC-derived CM is as efficient as fresh and cryopreserved rAM. CONCLUSION: Our findings suggest that rAM-MSCs and rAM-MSC derived CM can be effectively used to treat skin wounds in animals and correctly delivered to the damaged tissue using AM as a bioscaffold, either fresh or frozen.


Subject(s)
Amnion , Mesenchymal Stem Cells , Wound Healing , Animals , Rabbits , Female , Mesenchymal Stem Cells/cytology , Cell Differentiation , Culture Media, Conditioned/pharmacology , Mesenchymal Stem Cell Transplantation/methods , Skin/injuries , Skin/pathology , Pregnancy , Disease Models, Animal , Cells, Cultured , Transplantation, Homologous
12.
JASA Express Lett ; 4(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38717467

ABSTRACT

A long-standing quest in audition concerns understanding relations between behavioral measures and neural representations of changes in sound intensity. Here, we examined relations between aspects of intensity perception and central neural responses within the inferior colliculus of unanesthetized rabbits (by averaging the population's spike count/level functions). We found parallels between the population's neural output and: (1) how loudness grows with intensity; (2) how loudness grows with duration; (3) how discrimination of intensity improves with increasing sound level; (4) findings that intensity discrimination does not depend on duration; and (5) findings that duration discrimination is a constant fraction of base duration.


Subject(s)
Inferior Colliculi , Loudness Perception , Animals , Rabbits , Loudness Perception/physiology , Inferior Colliculi/physiology , Acoustic Stimulation/methods , Discrimination, Psychological/physiology , Auditory Perception/physiology , Neurons/physiology
13.
Article in German | MEDLINE | ID: mdl-38701800

ABSTRACT

In 2023, no new active pharmaceutical ingredients were released on the German market for horses and food-producing animals. Two established veterinary active pharmaceutical ingredients became available for additional species: The phosphorus compound butafosfan was also approved for horses, dogs, and cats and the mineral sodium chloride as an isotonic sodium chloride solution was also approved for rabbits and guinea pigs. In addition, for small animals, there were new releases of an agent (pergolidmesilate) in a novel pharmaceutical formulation and a lower content of the active ingredient, one drug (fluralaner) in a smaller package size as well as one drug (oxalic acid dehydrate) with a new route of administration. Furthermore, one combination of active ingredients (diprophylline+heptaminol) is available on the market for horses and food producing animals again.


Subject(s)
Veterinary Drugs , Animals , Horses , Germany , Dogs , Cats , Guinea Pigs , Rabbits
14.
Article in German | MEDLINE | ID: mdl-38701806

ABSTRACT

In 2023, 2 novel pharmaceutical agents for small animals were released on the German market: the structural but non-functional analog of the inhibitory neurotransmitter gamma-aminobutyric acid pregabalin with an anxiolytic active component and the dopamine agonist ropinirole in form of eye drops to induce vomiting. Two established active veterinary pharmaceutical ingredients became available for additional species: The phosphorus compound butafosfan was additionally approved for horses, dogs and cats and the mineral sodium chloride as an isotonic sodium chloride solution was also approved for rabbits and guinea pigs. In addition, for small animals, there were new releases of an agent (dexamethasone) in a novel pharmaceutical formulation, one drug with a new route of administration (hydrocortisone aceponate), one drug with a new content of the active ingredient (firocoxib) as well as one veterinary drug with a new combination of active ingredients in a novel pharmaceutical formulation (gentamicin+mometasone+posaconazole). Furthermore, one combination of active ingredients (diprophylline+heptaminol) is available on the market for small animals again.


Subject(s)
Veterinary Drugs , Animals , Dogs , Cats , Horses , Germany , Rabbits
15.
BMC Vet Res ; 20(1): 173, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702665

ABSTRACT

Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines' physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies' titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles.


Subject(s)
Horse Diseases , Mice, Inbred BALB C , Streptococcal Infections , Streptococcal Vaccines , Streptococcus equi , Streptococcus , Animals , Streptococcus equi/immunology , Horses , Rabbits , Streptococcal Infections/veterinary , Streptococcal Infections/prevention & control , Streptococcal Infections/microbiology , Streptococcal Infections/immunology , Mice , Horse Diseases/prevention & control , Horse Diseases/microbiology , Horse Diseases/immunology , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Female , Antibodies, Bacterial/blood , Adjuvants, Immunologic/administration & dosage , Vaccines, Inactivated/immunology
16.
Transpl Int ; 37: 12601, 2024.
Article in English | MEDLINE | ID: mdl-38694492

ABSTRACT

Controlled hypothermic storage (CHS) is a recent advance in lung transplantation (LTx) allowing preservation at temperatures higher than those achieved with traditional ice storage. The mechanisms explaining the benefits of CHS compared to conventional static ice storage (SIS) remain unclear and clinical data on safety and feasibility of lung CHS are limited. Therefore, we aimed to provide a focus review on animal experiments, molecular mechanisms, CHS devices, current clinical experience, and potential future benefits of CHS. Rabbit, canine and porcine experiments showed superior lung physiology after prolonged storage at 10°C vs. ≤4°C. In recent molecular analyses of lung CHS, better protection of mitochondrial health and higher levels of antioxidative metabolites were observed. The acquired insights into the underlying mechanisms and development of CHS devices allowed clinical application and research using CHS for lung preservation. The initial findings are promising; however, further data collection and analysis are required to draw more robust conclusions. Extended lung preservation with CHS may provide benefits to both recipients and healthcare personnel. Reduced time pressure between procurement and transplantation introduces flexibility allowing better decision-making and overnight bridging by delaying transplantation to daytime without compromising outcome.


Subject(s)
Lung Transplantation , Lung , Organ Preservation , Animals , Organ Preservation/methods , Lung Transplantation/methods , Humans , Swine , Lung/physiology , Dogs , Rabbits , Cryopreservation/methods
17.
Sci Data ; 11(1): 488, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734729

ABSTRACT

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.


Subject(s)
Herbivory , Transcriptome , Animals , Cattle/genetics , Female , Rabbits/genetics , Databases, Genetic , Deer/genetics , Equidae/genetics , Goats/genetics , Horses/genetics , Sheep/genetics
18.
Int J Mol Sci ; 25(9)2024 May 05.
Article in English | MEDLINE | ID: mdl-38732255

ABSTRACT

This research aimed to explore the healing impacts of Melittin treatment on gastrocnemius muscle wasting caused by immobilization with a cast in rabbits. Twenty-four rabbits were randomly allocated to four groups. The procedures included different injections: 0.2 mL of normal saline to Group 1 (G1-NS); 4 µg/kg of Melittin to Group 2 (G2-4 µg/kg Melittin); 20 µg/kg of Melittin to Group 3 (G3-20 µg/kg Melittin); and 100 µg/kg of Melittin to Group 4 (G4-100 µg/kg Melittin). Ultrasound was used to guide the injections into the rabbits' atrophied calf muscles following two weeks of immobilization via casting. Clinical measurements, including the length of the calf, the compound muscle action potential (CMAP) of the tibial nerve, and the gastrocnemius muscle thickness, were assessed. Additionally, cross-sectional slices of gastrocnemius muscle fibers were examined, and immunohistochemistry and Western blot analyses were performed following two weeks of therapy. The mean regenerative changes, as indicated by clinical parameters, in Group 4 were significantly more pronounced than in the other groups (p < 0.05). Furthermore, the cross-sectional area of the gastrocnemius muscle fibers and immunohistochemical indicators in Group 4 exceeded those in the remaining groups (p < 0.05). Western blot analysis also showed a more significant presence of anti-inflammatory and angiogenic cytokines in Group 4 compared to the others (p < 0.05). Melittin therapy at a higher dosage can more efficiently activate regeneration in atrophied gastrocnemius muscle compared to lower doses of Melittin or normal saline.


Subject(s)
Melitten , Muscle, Skeletal , Muscular Atrophy , Regeneration , Animals , Rabbits , Melitten/pharmacology , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Regeneration/drug effects , Muscular Atrophy/drug therapy , Muscular Atrophy/metabolism , Muscular Atrophy/etiology , Muscular Atrophy/pathology , Male
19.
Anat Histol Embryol ; 53(3): e13052, 2024 May.
Article in English | MEDLINE | ID: mdl-38735035

ABSTRACT

One crucial component of the optical system is the ciliary body (CB). This body secretes the aqueous humour, which is essential to maintain the internal eye pressure as well as the clearness of the lens and cornea. The histological study was designed to provide the morphological differences of CB and iris in the anterior eye chambers of the following vertebrate classes: fish (grass carp), amphibians (Arabian toad), reptiles (semiaquatic turtle, fan-footed gecko, ocellated skink, Egyptian spiny-tailed lizard, Arabian horned viper), birds (common pigeon, common quail, common kestrel), and mammals (BALB/c mouse, rabbit, golden hamster, desert hedgehog, lesser Egyptian jerboa, Egyptian fruit bat). The results showed distinct morphological appearances of the CB and iris in each species, ranging from fish to mammals. The present comparative study concluded that the morphological structure of the CB and iris is the adaptation of species to either their lifestyle or survival in specific habitats.


Subject(s)
Ciliary Body , Iris , Animals , Ciliary Body/anatomy & histology , Iris/anatomy & histology , Rabbits/anatomy & histology , Mice/anatomy & histology , Lizards/anatomy & histology , Vertebrates/anatomy & histology , Reptiles/anatomy & histology , Fishes/anatomy & histology , Birds/anatomy & histology , Anterior Chamber/anatomy & histology , Turtles/anatomy & histology , Carps/anatomy & histology , Mice, Inbred BALB C , Amphibians/anatomy & histology , Cricetinae , Quail/anatomy & histology , Hedgehogs/anatomy & histology , Columbidae/anatomy & histology , Mesocricetus/anatomy & histology
20.
Anat Histol Embryol ; 53(3): e13053, 2024 May.
Article in English | MEDLINE | ID: mdl-38735036

ABSTRACT

This study aimed to determine the morphometric measurements anatomically and CT images of skulls of healthy male and female rabbits during postnatal development, to analyse the data statistically and to demonstrate the structural changes in bone. A total of 40 rabbits (20 females and 20 males) were divided into four groups including prepubertal period (group I (0-1 month)), period between adolescence and adulthood (group II (3-5 month)) and later (young adult period as group III (1-3 years) and old adult period as group IV (3-5 years)), with five animals in each group. After the morphometric measurements, the surface area and volume values of the skull were calculated. The skulls were reconstructed using a 3D Slicer (5.0.2), which is used for 3D modelling. The cranial bones in each group were then crushed using a grinder so that the powdered samples were obtained for XRF (X-ray fluorescence technique). The p-value was statistically highly significant between group and gender (p < 0.001). In morphometric measurements, males were generally higher than females. Only PL, GBOC and GNB measurements were higher in females. The p-value between groups (in all measurements), between genders (in TL, GLN, FL, VL, OZB and GBN parameters) and between groups and genders (in TL, DL and VL parameters) was statistically highly significant (p < 0.001). The p-value between the groups, p-value between sexes and p-value between group and sex in Si, P, K, Ca, Ni, Zn, Sr, Sr and Ca/P elements were statistically significant (p < 0.001). Consequently, metric, volume and surface area measurements were taken through 3D modelling of skull bone in prepubertal period (group I), period between adolescence and adulthood (group II) and later (young adult period as group III and old adult period as group IV) of rabbits and the change in the mineral structure during postnatal development and effect of sex on this change were investigated. This might be the first study to assess both metric and mineral changes at four age intervals taken during the life span of rabbits.


Subject(s)
Imaging, Three-Dimensional , Skull , Tomography, X-Ray Computed , Animals , Rabbits/anatomy & histology , Rabbits/growth & development , Female , Male , Skull/anatomy & histology , Skull/diagnostic imaging , Skull/growth & development , Imaging, Three-Dimensional/veterinary , Tomography, X-Ray Computed/veterinary , Bone Density
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