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Topic:In Vivo
In vivo studies involving horses refer to research conducted within living organisms to understand various biological processes, disease mechanisms, and therapeutic interventions in equine species. These studies provide insights into the physiological and pathological responses of horses under natural conditions. In vivo research encompasses a range of investigations, including pharmacokinetics, disease modeling, and the evaluation of treatment efficacy. It often involves the use of controlled environments to simulate real-life scenarios while observing the effects of specific variables on equine health. This page gathers peer-reviewed research articles and scholarly studies that explore the methodologies, findings, and implications of in vivo research in horses, contributing to the advancement of equine science and veterinary medicine.
Quantitative Evaluation of Equine Articular Cartilage Using Cationic Contrast-Enhanced Computed Tomography. To investigate the diffusion trajectory of a cationic contrast medium (CA4+) into equine articular cartilage, and to assess normal and degenerative equine articular cartilage using cationic contrast-enhanced computed tomography (CECT). In the first experiment (Exp1), equine osteochondral specimens were serially imaged with cationic CECT to establish the diffusion time constant and time to reach equilibrium in healthy articular cartilage. In a separate experiment (Exp2), articular cartilage defects were created on the femoral trochlea (defect joint) in a juvenile horse, while the opposite joint...
Use of next generation sequencing to investigate the microbiota of experimentally induced wounds and the effect of bandaging in horses. To use next generation sequencing to characterize the microbiota of horses during healing of skin wounds in two anatomical locations (body and limb) known to present different healing patterns; and to investigate the impact of bandaging on bacterial communities of skin wounds located on the limbs of horses. Full-thickness skin wounds were created on the distal extremity of both thoracic limbs and on one lateral mid-thoracic wall of four healthy horses. Limb wounds were randomly assigned to bandaging or not. A full-thickness sample was collected with a biopsy punch from intact thorax and limb s...
Subchondral bone cyst surgical treatment using the application of stem progenitor cells combined with alginate hydrogel in small joints in horses. One of the most common reasons for horse lameness is subchondral bone cysts (SBCs), which are especially evident in young horse athletes. It is believed that SBC development is strongly associated with an individual's bone growth and/or bone microstructure impairment. Current methods of SBC treatment include pharmacological treatment or surgical procedures which may allow the bone within the cyst to rebuild and be restored to properly developed bone tissue. Thus, we propose filling the SBCs with a 3D complex of alginate hydrogel and autologous adipose derived mesenchymal stem cells (ASCs). We ...
Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis. Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining we...
Early luteal phase progestin concentration influences endometrial function in pregnant mares. In the horse, it is still unclear if and to what extent low progestin concentration contributes to early conceptus loss. In the present study, we have investigated if reduced or elevated progestin concentration in the early luteal phase influences endometrial function and conceptus development. We hypothesized that reduced progestin concentration via delayed downregulation of endometrial progesterone receptors (PR) influences endometrial function in healthy fertile mares while progestin substitution does not. Genitally healthy estrous mares (n = 8; age 4-14 years) were inseminated and trea...
Characterisation of the in vivo interactions between detomidine and methadone in horses: Pharmacokinetic and pharmacodynamic modelling. Pharmacokinetic (PK)/pharmacodynamic (PD) modelling offers new insights to design protocols for sedation and analgesia in standing horses. Objective: To evaluate the parameters and interactions between detomidine and methadone when given alone or combined in standing horses. Methods: Randomised, placebo-controlled, blinded, crossover. Methods: Eight adult healthy horses were given six treatments intravenously: saline (SAL); detomidine (5 μg/kg bwt; DET); methadone (0.2 mg/kg bwt; MET) alone or combined with detomidine (2.5 [MLD], 5 [MMD] or 10 [MHD] μg/kg bwt). Venous blood samples were ob...
Transrectal three-dimensional fetal volumetry and crown-rump length measurement during early gestation in mares: Intra- and inter-observer reliability and agreement. The aim of this study was to investigate if transrectal three-dimensional (3D) ultrasound is a reliable technique to measure equine fetal volume (FV) during early gestation in mares. In total 149 warmblood mares were examined once transrectally on days 45 ± 1 of pregnancy with a portable 3D ultrasound device (Voluson i, GE Healthcare, Zipf, Austria). The following measurements were performed: Two-dimensional (2D) and 3D crown-rump length (CRL), FV using Virtual Organ Computer-aided AnaLysis (VOCAL™) software with rotational angles of 6° and 30°. To analyze intra- and inter-observer re...
The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses. The equine herpesvirus type 1 (EHV-1) ORF1 and ORF71 genes have immune modulatory effects in vitro. Experimental infection of horses using virus mutants with multiple deletions including ORF1 and ORF71 showed promise as vaccine candidates against EHV-1. Here, the combined effects of ORF1 and ORF71 deletions from the neuropathogenic EHV-1 strain Ab4 on clinical disease and host immune response were further explored. Three groups of EHV-1 naïve horses were experimentally infected with the ORF1/71 gene deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or remained uninfected. In comparison t...
Mitochondrial DNA replication is initiated at blastocyst formation in equine embryos. Intracytoplasmic sperm injection is the technique of choice for equine IVF and, in a research setting, 18-36% of injected oocytes develop to blastocysts. However, blastocyst development in clinical programs is lower, presumably due to a combination of variable oocyte quality (e.g. from old mares), suboptimal culture conditions and marginal fertility of some stallions. Furthermore, mitochondrial constitution appears to be critical to developmental competence, and both maternal aging and invitro embryo production (IVEP) negatively affect mitochondrial number and function in murine and bovine emb...
Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes. The evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian order , with a view to understanding their impact on the evolution of modern equids (family ). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization, and time of activity. Our results show that subsequent to their ancestral divergence from rhinoceroses and tapirs, equids acquired four novel ERV lineages. We show that two of these ER...
Extracellular Vesicles in Joint Disease and Therapy. The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this approach is still in its infancy. As in joint diseases both inflammation and the associated articular tissue destruction are important factors, both the immune-suppressive and the regenerative properties of EVs are potentially advantageous characteristics for future therapy. There is, however, only limited knowledge on the basic features, such as numerical profile and function, of EVs in joint articular tissues in general and th...
Cyclooxygenase-2 is inhibited in prolonged luteal maintenance induced by intrauterine devices in mares. Treatment with intrauterine devices (IUD) prolongs luteal phases in mares, but the mechanism for this has not been fully elucidated. The aims of the present study were to examine how IUDs affect the uterus to induce longer luteal phases, particularly the role of cyclooxygenase-2 (COX-2) in the maintenance of the corpus luteum (CL). Twenty-seven reproductively normal mares were included: 12 were inseminated (AI), and 15 were fitted with IUDs. Blood samples for progesterone were obtained on Days 0, 3, 5, 7, 9, 11, 13, 14, and 15 (relative to day of ovulation). The groups were further divided int...
Comparison of incisional complications between skin closures using a simple continuous or intradermal pattern: a pilot study in horses undergoing ventral median celiotomy. Development of incisional complications following ventral median celiotomy might depend on suture pattern for skin closure. Methods: In this prospective study, 21 healthy male horses underwent celiotomy. Skin closure was either performed via a continuous percutaneous pattern (CO group; 5 warmbloods/5 ponies) or an intradermal pattern (ID group; 5 warmbloods/6 ponies). Follow-up examination of the incisional site included daily monitoring for edema, dehiscence, and drainage. Transcutaneous ultrasound was performed at Days 3, 6, and 10 as well as on Week 8 and 12 to evaluate size of edema and pr...
Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3-4 days. The purpose of this study was to determine if a low dose of diclazuril (0.5mg/kg of 1.56% diclazuril pellets) given to six healthy adult horses every 3-4 days for a total of five administrations would achieve steady-state plasma concentrations known to be inhibitory to Sarcocystis neurona and Neospora caninum. Blood was collected via venipuncture immediately before (trough concentrations) and 10h after (peak concentrations) each diclazuril administration and analysed by high-pressure liquid chromatography. The mean population-derived peak concentration was 0.284μg/mL and the mean terminal hal...
In vitro MSC function is related to clinical reaction in vivo. We recently demonstrated that intracellular xenogen-contaminated autologous MSCs (FBS) and non-xenogen-contaminated allogeneic (ALLO) MSCs caused an adverse clinical response after repeated intra-articular injection in horses, whereas autologous (AUTO) MSCs did not. Our current objective was to use clinical data from the previous study to compare MSC stemness against adverse response indicated by synovial total nucleated cell count (TNCC) following intra-articular MSC injection. Stemness, quantified by a trilineage differentiation (TLD) score; immunomodulation, quantified by mixed lymphocyte ...
Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2×2 factorial trial. Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial n...
Pharmacokinetics of Metformin in Combination With Sitagliptin in Adult Horses After Enteral Administration. Insulin dysregulation (ID) is a common metabolic disorder in horses. Recently, incretin hormone release has been suggested to be involved in ID in horses. In human medicine, metformin and sitagliptin are commonly used in combination for metabolic syndrome. This combination could be useful in treating ID in horses. However, no pharmacokinetics data have been reported in this species. The objective of the present study was to establish the plasma concentration-time profile and to derive pharmacokinetics data for a combination of metformin and sitagliptin in horses after enteral administration. S...
Use of an aiming device and computed tomography for assisted debridement of subchondral cystic lesions in the limbs of horses. To describe the use of an aiming device (AD) and computed tomography (CT) for preoperative planning and intraoperative guided debridement of subchondral cystic lesions (SCL) in the limbs of horses and to determine the outcome 12 months after surgery. Methods: Prospective case series. Methods: Twelve horses referred because of lameness caused by 1 or 2 SCL (total of 14 SCL). Methods: All horses underwent CT-guided debridement of the SCL. The entry point of the drill bit and direction of drilling were planned and controlled by using a series of CT images and the AD. The SCL were curetted and fil...
Histological and Radiographic Evaluation of Equine Bone Structure after Implantation of Castor Oil Polymer. The main purpose of this study was to evaluate the characteristics of a vegetal polymeric biomaterial intended for bone substitution in horses and to investigate the responses of the equine third metacarpal bone to biomaterial implantation. Methods: Six horses were submitted to osteotomy on the dorsal aspect of the left and right third metacarpal bones; one bone defect was randomly selected for treatment with biopolymer, while the other was left untreated and served as a control. Bone density was monitored radiographically after surgery and bone biopsy fragments were collected at the end...
Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses. Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. Methods: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses ...
Evaluation of an in-clinic dry chemistry analyzer for canine, equine, and feline plasma samples. Method validation studies characterize the performance of new laboratory methods relative to established methods using quality guidelines in order to define the new method's performance characteristics and to identify differences that could influence data interpretation. We investigated the performance of an in-clinic dry chemistry analyzer (Catalyst One, IDEXX) for measuring 19 routine plasma biochemistry analytes in dogs, cats, and horses. We analyzed 2 levels of quality control material (QCM) in duplicate twice daily for 5 d to determine the coefficient of variation (CV), percent bias, ob...
Diffusion of charged and uncharged contrast agents in equine mandibular condylar cartilage is not affected by an increased level of sugar-induced collagen crosslinking. Nutrition of articular cartilage relies mainly on diffusion and convection of solutes through the interstitial fluid due to the lack of blood vessels. The diffusion is controlled by two factors: steric hindrance and electrostatic interactions between the solutes and the matrix components. Aging comes with changes in the cartilage structure and composition, which can influence the diffusion. In this study, we treated fibrocartilage of mandibular condyle with ribose to induce an aging-like effect by accumulating collagen crosslinks. The effect of steric hindrance or electrostatic forces on the d...
Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection. Doping control is an important and indispensable aspect of fair horse racing; genetic doping has been recently included to this. In this study, we aimed to develop a detection method of gene doping. A plasmid cloned with human erythropoietin gene (p.hEPO, 250 μg/head) was intramuscularly injected into a microminipig. Subsequently, p.hEPO was extracted from 1 mL of plasma and detected by droplet digital polymerase chain reaction. Results: The results confirmed that the maximum amount of plasmid was detected at 15 min after administration and the majority of the plasmid was degraded in the b...
Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways. Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is characterized by myofibrillar disarray and ectopic desmin aggregates of unknown origin. To investigate the pathophysiology of MFM, we compared resting and 3 h postexercise transcriptomes of gluteal muscle and the resting skeletal muscle proteome of MFM and control Arabian horses with RNA sequencing and isobaric tags for relative and absolute quantitation analyses. Three hours after exercise, 191 genes were identified as differentially expressed (DE) in MFM vs. control muscle with >1 log fold change (FC) in genes involve...
Bone Marrow Aspiration Does Not Induce a Measurable Pain Response Compared to Sham Procedure. Bone marrow is commonly collected from horses for regenerative medicine applications. Little information is available regarding pain experienced by the horse during bone marrow aspiration. The objective of this study was to characterize horse reaction and pain response during bone marrow aspiration (BMA) compared to a sham (SHAM) procedure. We hypothesized there would be significantly greater horse reaction or pain response measured by salivary cortisol, heart rate variability, and depth and duration of sedation between BMA and SHAM. Twelve university owned horses underwent a BMA and sham proc...
Bursting strength of surgeon’s and self-locking knots for closure of ventral midline celiotomy in horses. To compare the bursting strength and failure mode of ventral midline celiotomy closed with a simple continuous suture pattern with 1 of 2 knot combinations, a novel self-locking knot combination of a forwarder start with an Aberdeen end knot (F-A) and a traditional combination of a surgeon's start with a surgeon's end knot (S-S). Methods: Ex vivo experimental. Methods: Equine cadavers (n = 14). Methods: A 20-cm ventral midline celiotomy was created in 14 equine cadavers. Horses were assigned to celiotomy closure with an F-A or S-S knot combination. Prior to closure, a 200-L inflatable blad...
Dynamic changes in gene expression and signalling during trophoblast development in the horse. Equine chorionic girdle trophoblast cells play important endocrine and immune functions critical in supporting pregnancy. Very little is known about the genes and pathways that regulate chorionic girdle trophoblast development. Our aim was to identify genes and signalling pathways active in vivo in equine chorionic girdle trophoblast within a critical 7-days window. We exploited the late implantation of the equine conceptus to obtain trophoblast tissue. An Agilent equine 44K microarray was performed using RNA extracted from chorionic girdle and chorion (control) from equine pregnancy days 27, ...
Dynamic changes in gene expression and signalling during trophoblast development in the horse. Equine chorionic girdle trophoblast cells play important endocrine and immune functions critical in supporting pregnancy. Very little is known about the genes and pathways that regulate chorionic girdle trophoblast development. Our aim was to identify genes and signalling pathways active in vivo in equine chorionic girdle trophoblast within a critical 7-days window. We exploited the late implantation of the equine conceptus to obtain trophoblast tissue. An Agilent equine 44K microarray was performed using RNA extracted from chorionic girdle and chorion (control) from equine pregnancy days 27, ...
Cytological and bacteriological sampling from filters used for embryo recovery to evaluate the uterine status of donor mares. While testing for uterine bacterial infection is usually performed prior to artificial insemination (AI), samples taken during or after embryo flushing are generally not assessed either in subfertile and old mares or in fertile mares, even though knowledge of the status of the uterine environment in which the embryo is to develop would help to predict the outcome of embryo transfer programmes. The presence of bacteria and inflammatory cells in the liquid retained in the filter after uterine flushing in donors was determined at the moment of embryo recovery. Primarily, a group of mares (n = 8) ...
