Small Animal Research Articles

Retrospective evaluation of the utility of shock index to determine the presence of congestive heart failure in dogs with myxomatous mitral valve disease (2019-2021): 98 cases.

To calculate the shock index (SI) in dogs with myxomatous mitral valve disease (MMVD) and to evaluate its use to predict the presence of congestive heart failure (CHF). Retrospective study. Small animal university veterinary teaching hospital. Ninety-eight dogs with MMVD and 20 healthy dogs as part of a control group. Heart rate (HR) and systolic blood pressure (SBP) were recorded, and SI was calculated by dividing HR by SBP for each dog. The mean (SD) HR, SBP, and SI were 123/min (32.6), 147mmHg (21.5), and 0.86 (0.3), respectively, for dogs with MMVD and 98/min (20.9), 145mmHg (18.7), and 0.68 (0.13), respectively, for control dogs. Dogs with MMVD had a significantly higher HR compared with control dogs (P<0.01), and an elevation in HR was seen as the severity of MMVD increased. Dogs in stage B2 and C/D MMVD had a significantly higher SI value compared with control dogs (P=0.04 and P<0.01, respectively). SI was significantly higher in dogs in stage C/D MMVD compared with dogs in stage B2 MMVD (P<0.01). Ten of 98 (10%) dogs had an arrhythmia. HR, SBP, and SI were not significantly different between dogs with and without arrhythmias (P=0.13, P=0.57, and P=0.07, respectively), but significantly more dogs with CHF had an arrhythmia (P=0.01). SI (area under the curve [AUC]: 0.98) and HR (AUC: 0.95) were excellent indicators for the presence of CHF. An optimal SI cutoff value ≥1.1 had 92% sensitivity and 95% specificity for predicting the presence of CHF, and an optimal HR cutoff value of ≥157/min had 92% sensitivity and 93% specificity for the prediction of CHF. When there are compatible clinical signs, SI values ≥1.1 may suggest the presence of CHF in dogs with MMVD.

A Review on Techniques of Blood Withdrawal in Experimental Small Animals

In preclinical research, experimental studies in small animals like pharmacokinetics/ toxicokinetics, serum biochemistry and hematology necessitate the biological matrix sampling to estimate drug level, serum enzyme, and blood parameters respectively. The biological matrix is withdrawn from experimental animals by employing the recommended blood collection technique and must be conducted in compliance with the ethical guidelines. It has demanded a minimal painful and least stressful procedures, which can be achieved using inhalant/parenteral anesthesia and/or proper restraint technique. This leads to better experimental outcome. The study personnel conducting blood withdrawal must be well-versed. All these procedures must be approved by IAEC protocol and should include scientist and study personnel names who are involved in animal handling and blood withdrawal. In this review, the different techniques of blood withdrawal from small animals, including collection guidelines, limit volumes and recovery periods, and advantages and disadvantages of sites used for blood collection are demonstrated and discussed.

From lab bench to hope: a review of gene therapies in clinical trials for Parkinson's disease and challenges.

Parkinson's disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer's disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients' quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD.

Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet

The stomach-derived hormone ghrelin regulates essential physiological functions. The ghrelin receptor (GHSR) has ligand-independent actions; therefore, GHSR gene deletion may be a reasonable approach to investigate the role of this system in feeding behaviors and diet-induced obesity (DIO). Here, we investigate the effects of a long-term (12-month) high-fat (HFD) versus regular diet on obesity-related measures in global GHSR-KO and wild-type (WT) Wistar male and female rats. Our main findings are that the GHSR gene deletion protects against DIO and decreases food intake during HFD in male but not in female rats. GHSR gene deletion increases thermogenesis and brain glucose uptake in male rats and modifies the effects of HFD on brain glucose metabolism in a sex-specific manner, as assessed with small animal positron emission tomography. We use RNA-sequencing to show that GHSR-KO rats have upregulated expression of genes responsible for fat oxidation in brown adipose tissue. Central administration of a novel GHSR inverse agonist, PF-5190457, attenuates ghrelin-induced food intake, but only in male, not in female mice. HFD-induced binge-like eating is reduced by inverse agonism in both sexes. Our results support GHSR as a promising target for new pharmacotherapies for obesity.

High-resolution hybrid micro-CT imaging pipeline for mouse brain region segmentation and volumetric morphometry.

Brain region segmentation and morphometry in humanized apolipoprotein E (APOE) mouse models with a human NOS2 background (HN) contribute to Alzheimer's disease (AD) research by demonstrating how various risk factors affect the brain. Photon-counting detector (PCD) micro-CT provides faster scan times than MRI, with superior contrast and spatial resolution to energy-integrating detector (EID) micro-CT. This paper presents a pipeline for mouse brain imaging, segmentation, and morphometry from PCD micro-CT. We used brains of 26 mice from 3 genotypes (APOE22HN, APOE33HN, APOE44HN). The pipeline included PCD and EID micro-CT scanning, hybrid (PCD and EID) iterative reconstruction, and brain region segmentation using the Small Animal Multivariate Brain Analysis (SAMBA) tool. We applied SAMBA to transfer brain region labels from our new PCD CT atlas to individual PCD brains via diffeomorphic registration. Region-based and voxel-based analyses were used for comparisons by genotype and sex. Together, PCD and EID scanning take ~5 hours to produce images with a voxel size of 22 μm, which is faster than MRI protocols for mouse brain morphometry with voxel size above 40 μm. Hybrid iterative reconstruction generates PCD images with minimal artifacts and higher spatial resolution and contrast than EID images. Our PCD atlas is qualitatively and quantitatively similar to the prior MRI atlas and successfully transfers labels to PCD brains in SAMBA. Male and female mice had significant volume differences in 26 regions, including parts of the entorhinal cortex and cingulate cortex. APOE22HN brains were larger than APOE44HN brains in clusters from the hippocampus, a region where atrophy is associated with AD. This work establishes a pipeline for mouse brain analysis using PCD CT, from staining to imaging and labeling brain images. Our results validate the effectiveness of the approach, setting a foundation for research on AD mouse models while reducing scanning durations.

#1887 Comparison of the efficacy of preservation at 22°C versus 4°C in warm ischemic kidneys from MHC-inbred CLAWN miniature swine

Abstract Background and Aims Static cold preservation, the standard in transplantation, is primarily aimed at reducing metabolic and oxygen demand. Kidney transplantation from donors after cardiac death (DCD) addresses the shortage of donor organs, but these kidneys are susceptible to cold preservation. A previous study using small animal models demonstrated the potential benefits of preserving DCD kidneys at a warmer temperature of 22°C using extracellular-type solutions (Iwai S., PLoS One 2012). Based on this foundational research, our study aimed to evaluate the efficacy of preserving warm ischemic kidneys at temperatures of either 4°C or 22°C using preclinical large animal miniature swine models. Method After 2 hours of warm ischemia, the pig kidneys were preserved for 60 minutes at either 4°C or 22°C with extracellular-type solutions (ETK®). In Experiment 1, these preserved kidneys underwent ex-vivo perfusion for 120 minutes at 37°C with a mean arterial pressure of 85 mmHg. This perfusion used a Ringer's solution supplemented with red blood cells, aiming to determine the early functionality of kidneys subjected to 2-hour warm ischemia in transplantation and to assess whether preservation at 4°C or 22°C could maintain renal function during the acute postoperative period (n = 3 in each group). During this period, both physiological parameters (renal blood flow, intrarenal resistance, and urine output) and metabolic parameters (oxygen consumption) were evaluated. In Experiment 2, kidneys that underwent similar warm ischemia and preservation procedures were transplanted into MHC-matched recipients. These recipients received continuous tacrolimus treatment for 12 days to minimize rejection due to minor antigen differences. After transplantation, renal function was monitored and assessed by serum creatinine levels and renal biopsies for 14 days (n = 3 in each group). Results Experiment 1 demonstrated that kidneys subjected to 2 hours of warm ischemia and then preserved at 22°C had better physiological and metabolic indices during a subsequent 2-hour ex-vivo perfusion compared to those preserved at 4°C. The results were as follows: 22°C vs. 4°C—mean renal blood flow (27 ± 5 vs. 10 ± 0 ml/min), intrarenal resistance (3.5 ± 0.5 vs. 8.7 ± 0.1 mmHg/ml/min), total urine volume (14 ± 5 vs. 5 ± 4 ml), and oxygen consumption (224 ± 39 vs. 93 ± 16 ml/min/g). Importantly, there was no complete cessation of blood flow in either group, indicating the potential for long-term evaluation using a transplantation model. In Experiment 2, kidneys preserved at 22°C resulted in significantly lower peak post-transplant serum creatinine levels compared to those preserved at 4°C (3.9 ± 0.6 mg/dl vs 8.9 ± 0.3 mg/dl, p = 0.0015). There was a marked decrease in the area under the curve of creatinine from day 0 to day 14, with a 36% reduction from 61 mg/dL per day in the 4°C group to 39 mg/dL per day in the 22°C group. Renal biopsies performed on post-operative day 4 revealed extensive necrosis in the renal tubules of kidneys stored at 4°C. In contrast, kidneys preserved at 22°C showed more localized damage. In addition, PCNA staining indicated accelerated regeneration of the tubular epithelium in kidneys preserved at 22°C. Conclusion This study demonstrates that kidneys subjected to 2 hours of warm ischemia from MHC-inbred miniature swine are more effectively preserved at 22°C than at 4°C when using an extracellular-type solution. To our knowledge, this is the first report demonstrating the efficacy of organ preservation at 22°C in clinically relevant, large animal models. From the evaluation of ex-vivo perfusion of preserved kidneys, it was suggested that kidneys preserved at 22°C maintain better blood perfusion to severely ischemic kidneys immediately after transplantation, which leads to the rapid recovery of renal function of acute kidney injury. Future research will focus on elucidating the mechanisms underlying the superior outcomes associated with 22°C preservation. In addition, investigations will be conducted to determine whether similar benefits can be achieved using intracellular-type solutions, which are more commonly used in renal transplantation.

Chelator boosted tumor-retention and pharmacokinetic properties: development of 64Cu labeled radiopharmaceuticals targeting neurotensin receptor.

Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu.

Osteoarthritis, adipokines and the translational research potential in small animal patients

Osteoartritis (OA) is a debilitating disease affecting both humans and animals. In the early stages, OA is characterized by damage to the extracellular matrix (ECM) and apoptosis and depletion of chondrocytes. OA progression is characterized by hyaline cartilage loss, chondrophyte and osteophyte formation, thickening of the joint capsule and function loss in the later stages. As the regenerative potential of cartilage is very limited and osteoarthritic changes are irreversible, prevention of OA, modulation of existing osteoarthritic joint inflammation, reducing joint pain and supporting joint function are the only options. Progression of OA and pain may necessitate surgical intervention with joint replacement or arthrodesis as end-stage procedures. In human medicine, the role of adipokines in the development and progression of OA has received increasing interest. At present, the known adipokines include leptin, adiponectin, visfatin, resistin, progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin. Adipokines have been demonstrated to play a pivotal role in joint homeostasis by modulating anabolic and catabolic balance, autophagy, apoptosis and inflammatory responses. In small animals, in terms of dogs and cats, naturally occurring OA has been clearly demonstrated as a clinical problem. Similar to humans, the etiology of OA is multifactorial and has not been fully elucidated. Humans, dogs and cats share many joint related degenerative diseases leading to OA. In this review, joint homeostasis, OA, adipokines and the most common joint diseases in small animals leading to naturally occurring OA and their relation with adipokines are discussed. The purpose of this review is highlighting the translational potential of OA and adipokines research in small animal patients.

CdTe XG-Cam: A new high-resolution x-ray and gamma-ray camera for studies of the pharmacokinetics of radiopharmaceuticals in small animals.

The recent emergence of targeted radionuclide therapy has increased the demand for imagers capable of visualizing pharmacokinetics in developing radiopharmaceuticals in the preclinical phase. Some radionuclides emit hard x-rays and gamma-rays below 100 keV, in which energy range the performance of conventional NaI scintillators is poor. Multipinhole collimators are also used for small animal imaging with a good spatial resolution but have a limited field of view (FOV). In this study, a new imager with high sensitivity over a wide FOV in the low-energy band ( 100 keV) was developed for the pharmacokineticstudy. We developed an x-ray and gamma-ray camera for high-resolution spectroscopy, named "CdTe XG-Cam," equipped with a cadmium telluride semiconductor detector and a parallel-hole collimator using a metal 3D printer. To evaluate the camera-system performance, phantom measurements with single and dual nuclides ( , , and were performed. The performance for in vivo imaging was evaluated using tumor-bearing mice to which a nuclide ( or administered. We simultaneously obtained information on and , which emit emission lines in the low-energy band with peak energies close to each other (23-26 keV for and 27-31 keV for , and applied an analytical method based on spectral model fitting to determine the individual radioactivities accurately. In the small animal imaging, the distributions of the nuclide in tumors were accurately quantified and time-activity curves in tumors areobtained. The demonstrated capability of our system to perform in vivo imaging suggests that the camera can be used for applications of pharmacokineticsresearch.

Агонисты альфа-2адренорецепторов. Дексмедетомидин

Dexmedetomidine is a selective alpha2-adrenoreceptor agonist with a powerful sedative effect and analgesic properties. High selectivity of dexmedetomidine (1620:1) makes it the optimal drug among all representatives of the alpha-2adrenoreceptor agonist class for use in relatively small animals. Dexmedetomidine is currently the most popular sedative used for premedication and sedation, as well as in multimodal analgesia in a constant-rate infusion mode in intensive care. In 2024, a domestic drug with the trade name «Dexody» of the pharmaceutical company «Apicenna» with the active substance dexmedetomidine was registered. The drug is a complete analogue of the original drug and is approved for use in veterinary medicine.

Canine Euthanasia's Trend Analysis during Thirty Years (1990-2020) in Italy: A Veterinary Hospital as Case Study.

This study aimed to investigate changes in the number of, and reasons for, requests for dogs' euthanasia over the last thirty years. Data (breed, age, gender, neuter status, manner, and cause of death) from dogs' euthanasia registered between 1990 and 2020 in a small animals' veterinary hospital were analyzed. The overall period examined has been split into two terms (T1 = 1990-2004 and T2 = 2005-2020) considering the introduction and enforcement of Law 189/2004. During the whole period examined, a significant increasing trend in euthanasia cases has been recorded (p = 0.027). Comparing the two terms, we observed significant differences regarding variables such as age, breed, reproductive status, and ownership. The number of euthanized dogs was significantly higher in T1 than in T2. Dogs euthanized in T2 were older than dogs in T1. A high percentage of the euthanized dogs were crossbred and stray dogs. Additionally, the number of neutered/spayed dogs was significantly higher. Regarding the cause of death, a significantly higher percentage of neoplastic processes was detected in T2. The data here reported suggest a potential influence of Law 189/2004. This law in Italy has proven to be a legal milestone that has influenced the decision-making process between euthanasia and natural death.

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

Abstract The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration. However, it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains. This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals. Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin. Recently, we showed that the PINK1 kinase is selectively expressed as a truncated form (PINK1–55) in the primate brain. In the present study, we used multiple antibodies, including our recently developed monoclonal anti-PINK1, to validate the selective expression of PINK1 in the primate brain. We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages, which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains. PINK1 was enriched in the membrane-bound fractionations, whereas Parkin was soluble with a distinguishable distribution. Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes, though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress. These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

Microbial Colonization of Explants after Osteosynthesis in Small Animals: Incidence and Influencing Factors.

Despite recent advancements in antibiotics, hygienic measures, and peri-operative systemic antibiotics, post-operative infections in osteosynthesis remain prevalent and continue to be among the most common surgical complications, leading to delayed fracture healing, osteomyelitis, implant loosening, and loss of function. Osteosynthesis implants are routinely utilized in veterinary medicine and the current study investigates the microbial colonization of implants following osteosynthesis in small animals, along with its incidence and influencing factors. The results are analyzed in regard to correlations between infection, patient, disease progression, and radiographic images, as well as other factors that may promote infection. Seventy-one explants from sixty-five patients were examined and evaluated for microbial colonization. Factors like body weight and age, location and type of plate and additional injuries like lung lesions, the surgeon's experience, or the number of people present during the surgical procedure seem to influence the development of an infection. Of the animals, 60% showed osteolytic changes and 73.3% of those with dysfunctional mobility had an implant infection. Microorganisms were detected in almost 50% of the explants, but a clinically relevant infection was only present in five patients (7.3%), suggesting that the presence of microorganisms on an implant does not necessarily lead to treatment complications.

Abdominocentesis and intra-abdominal pressure measurement in small animals.

To provide a video tutorial detailing how to perform "blind" and ultrasound-guided abdominocentesis for diagnostic and therapeutic guidance, and to provide a brief demonstration of intra-abdominal pressure measurement (IAP). Any cat or dog with suspicion of free abdominal effusion or patients requiring measurement of IAP. Abdominocentesis should be performed when there is high suspicion for peritoneal effusion based on physical exam and/or diagnostic imaging. The 4-quadrant tap uses 20-gauge or larger needles placed blindly in ≥ 1 of the 4 quadrants of the abdomen to collect abdominal fluid. In contrast, ultrasound allows visualization of fluid in the abdomen prior to percutaneous insertion of a needle and syringe to collect fluid. Regardless of collection technique, fluid should have immediate cytologic analysis and later can be submitted for biochemical parameters, additional cellular analysis by a pathologist, and culture and sensitivity (in rare cases if indicated). Intravesicular bladder pressure measurement using a manometer-urinary catheter system approximates the IAP when there is concern for organ hypoperfusion and compartment syndrome. Abdominocentesis can be performed with and without the use of ultrasound guidance. Intravesicular bladder pressure measurement is used to diagnose and trend IAP values before and after treatments are performed. Abdominocentesis is a simple and safe technique that all small animal clinicians should be comfortable performing. Effusion sampling can guide further diagnostics and treatments. Measurement of IAP is simple and requires no specialized equipment.

An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice

BackgroundHypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment.MethodsPol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood–brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated.ResultsThis hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients.ConclusionOur study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.Graphical

Syrian Hamsters Model Does Not Reflect Human-like Disease after Aerosol Exposure to Encephalitic Alphaviruses.

Venezuelan (VEE), eastern (EEE), and western (WEE) equine encephalitis viruses are encephalitic New World alphaviruses that cause periodic epizootic and epidemic outbreaks in horses and humans that may cause severe morbidity and mortality. Currently there are no FDA-licensed vaccines or effective antiviral therapies. Each year, there are a limited number of human cases of encephalitic alphaviruses; thus, licensure of a vaccine or therapeutic would require approval under the FDA animal rule. Approval under the FDA animal rule requires the disease observed in the animal model to recapitulate what is observed in humans. Currently, initial testing of vaccines and therapeutics is performed in the mouse model. Unfortunately, alphavirus disease manifestations in a mouse do not faithfully recapitulate human disease; the VEEV mouse model is lethal whereas in humans VEEV is rarely lethal. In an effort to identify a more appropriate small animal model, we evaluated hamsters in an aerosol exposure model of encephalitic alphavirus infection. The pathology, lethality, and viremia observed in the infected hamsters was inconsistent with what is observed in NHP models and humans. These data suggest that hamsters are not an appropriate model for encephalitic alphaviruses to test vaccines or potential antiviral therapies.

Harnessing the potential of monocytes/macrophages to regenerate tissue engineered vascular grafts.

Cell-free tissue-engineered vascular grafts provide a promising alternative to treat cardiovascular disease but timely endothelialization is essential for ensuring patency and proper functioning post-implantation. Recent studies from our lab showed that blood cells like monocytes (MCs) and macrophages (Mφ) may contribute directly to cellularization and regeneration of bioengineered arteries in small and large animal models. While MCs and Mφ are leukocytes that are part of the innate immune response, they share common developmental origins with endothelial cells (ECs) and are known to play crucial roles during vessel formation (angiogenesis) and vessel repair after inflammation/injury. They are highly plastic cells that polarize into proinflammatory and anti-inflammatory phenotypes upon exposure to cytokines; and differentiate into other cell types, including EC-like cells, in the presence of appropriate chemical and mechanical stimuli. This review focuses on the developmental origins of MCs and ECs; the role of MCs and Mφ in vessel repair/regeneration during inflammation/injury; and the role of chemical signaling and mechanical forces in Mφ inflammation that mediates vascular graft regeneration. We postulate that comprehensive understanding of these mechanisms will better inform the development of strategies to coax MCs/Mφ into endothelializing the lumen and regenerate the smooth muscle layers of cell-free bioengineered arteries and veins that are designed to treat cardiovascular diseases and perhaps the native vasculature as well.

Anesthesia and Analgesia Recommended for Painful Procedures in Small Animals

The non-invasive but painful and invasive procedures are frequently performed in experimental animal studies, such as blood withdrawal, route of administration, and surgical procedures. Most of these procedures commonly conducted under anesthesia and/or analgesia and should be complied with the ethical requirements. However, pain is difficult to assess in animals, therefore, it is advisable to provide the analgesics pre-emptively or if painful condition is expected. Preanesthetic like tranquilizer is generally used to reduce the stress in animal and further it also aids in the smooth induction of anesthesia and recovery. In view of this, the objective is to demonstrate and discuss the guidelines of anesthesia and analgesia in small animals, especially mouse and rat with principal focus to ethical purview. These guidelines can be applicable to the animal house facility, pharmacology laboratory, and to a large extent for veterinary care.

Residency program factors affecting ACVS board examination pass rates from 2017 to 2021: A survey of ACVS small animal surgery residency programs.

To identify small animal surgery (SAS) residency program factors associated with board examination pass rates for the American College of Veterinary Surgeons (ACVS) board certification examinations. Online survey. Program directors of ACVS-registered SAS residency programs. An online survey was distributed to eligible 2021 ACVS SAS residency program directors. Respondents provided program information and Phase I and Phase II board examination pass rate data from 2017 to 2021. Programs were grouped based on overall combined board examination pass rates as "excellent" (≥90%) versus "adequate" (<90%). Data were analyzed using recursive partitioning. Responses from 36 ACVS SAS residency programs (18 private practice [PP], 18 academic programs [AP]) were included. Pass rates were considered "excellent" for 17/36 programs (11/17 AP, 6/17 PP). The strongest indicator of "excellent" programs was most mentors participating in rounds >75% of the time. Of those, the second indicator of "excellent" programs was a soft tissue caseload of <7 surgeries/resident/week. If the soft tissue caseload was >7 surgeries/resident/week, a high orthopedic caseload (>9 surgeries/resident/week) was indicative of "excellent" programs. If most mentors were not participating in rounds >75% of the time, APs were more likely to be "excellent." SAS APs may have higher ACVS board examination pass rates. Mentor involvement, caseload, and residency practice type may influence board examination pass rates. ACVS SAS residency programs' board examination pass rates may improve by optimizing mentor involvement and caseload regardless of practice type.

FLASC – Fast Localized Abdominal Scan in Cattle

Rapid ultrasound examination has been used in human emer­gency medicine and adapted to small animal (FAST) and equine medicine (FLASH) for assessment of trauma or colic. Fast Lo­calized Abdominal Scan in Cattle (FLASC) is a focused assess­ment using the ultrasound that I have adapted to assist with all of my examinations when I do not have a clear idea what is causing clinical signs. This exam is tailored toward the most common things I find in beef cattle, but can be useful with all classes of cattle to assist in diagnosis.