Full and Partial Mid-substance ACL Rupture Using Mechanical Tibial Displacement in Male and Female Mice.

The anterior cruciate ligament (ACL) is the most commonly injured knee ligament. Surgical reconstruction is the gold standard treatment for ACL ruptures, but 20-50% of patients develop post-traumatic osteoarthritis (PTOA). ACL rupture is thus a well-recognized etiology of PTOA; however, little is known about the initial relationship between ligamentous injury and subsequent PTOA. The goals of this project were to: (1) develop both partial and full models of mid-substance ACL rupture in male and female mice using non-invasive mechanical methods by means of tibial displacement; and (2) to characterize early PTOA changes in the full ACL rupture model. A custom material testing system was utilized to induce either partial or full ACL rupture by means of tibial displacement at 1.6 or 2.0 mm, respectively. Mice were euthanized either (i) immediately post-injury to determine rupture success rates or (ii) 14 days post-injury to evaluate early PTOA progression following full ACL rupture. Our models demonstrated high efficacy in inciting either full or partial ACL rupture in male and female mice within the mid-substance of the ACL. These tools can be utilized for preclinical testing of potential therapeutics and to further our understanding of PTOA following ACL rupture.

Phytochemical compound PB125 attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a model of musculoskeletal decline.

Impaired mitochondrial function and disrupted proteostasis contribute to musculoskeletal dysfunction. However, few interventions simultaneously target these two drivers to prevent musculoskeletal decline. Nuclear factor erythroid 2-related factor 2 (Nrf2) activates a transcriptional programme promoting cytoprotection, metabolism, and proteostasis. We hypothesized daily treatment with a purported Nrf2 activator, PB125, in Hartley guinea pigs, a model of musculoskeletal decline, would attenuate the progression of skeletal muscle mitochondrial dysfunction and impaired proteostasis and preserve musculoskeletal function. We treated 2- and 5-month-old male and female Hartley guinea pigs for 3 and 10 months, respectively, with the phytochemical compound PB125. Longitudinal assessments of voluntary mobility were measured using Any-MazeTM open-field enclosure monitoring. Cumulative skeletal muscle protein synthesis rates were measured using deuterium oxide over the final 30 days of treatment. Mitochondrial oxygen consumption in soleus muscles was measured using high resolution respirometry. In both sexes, PB125 (1) increased electron transfer system capacity; (2) attenuated the disease/age-related decline in coupled and uncoupled mitochondrial respiration; and (3) attenuated declines in protein synthesis in the myofibrillar, mitochondrial and cytosolic subfractions of the soleus. These effects were not associated with statistically significant prolonged maintenance of voluntary mobility in guinea pigs. Collectively, treatment with PB125 contributed to maintenance of skeletal muscle mitochondrial respiration and proteostasis in a pre-clinical model of musculoskeletal decline. Further investigation is necessary to determine if these documented effects of PB125 are also accompanied by slowed progression of other aspects of musculoskeletal dysfunction. KEY POINTS: Aside from exercise, there are no effective interventions for musculoskeletal decline, which begins in the fifth decade of life and contributes to disability and cardiometabolic diseases. Targeting both mitochondrial dysfunction and impaired protein homeostasis (proteostasis), which contribute to the age and disease process, may mitigate the progressive decline in overall musculoskeletal function (e.g. gait, strength). A potential intervention to target disease drivers is to stimulate nuclear factor erythroid 2-related factor 2 (Nrf2) activation, which leads to the transcription of genes responsible for redox homeostasis, proteome maintenance and mitochondrial energetics. Here, we tested a purported phytochemical Nrf2 activator, PB125, to improve mitochondrial function and proteostasis in male and female Hartley guinea pigs, which are a model for musculoskeletal ageing. PB125 improved mitochondrial respiration and attenuated disease- and age-related declines in skeletal muscle protein synthesis, a component of proteostasis, in both male and female Hartley guinea pigs.

Nasal Smooth Muscle Hamartoma in a Dog: a Novel Subtype.

A 3-year-old, female spayed, Pug-cross dog presented with a 2-year history of nasal congestion and focal facial deformity. Complete surgical excision was elected following nasopharyngoscopy, endoscopic biopsy and subsequent computed tomography (CT) scan. Nasopharyngoscopy revealed a friable, polypoid mass of the right nasal conchae occluding the right nasal passage. Biopsies of the mass showed expansion of the submucosa by dense bundles of well-differentiated smooth muscle cells that were strongly immunoreactive for ⍺-smooth muscle actin and desmin. Post-procedure CT revealed a large space-occupying mass in the nasal cavity with minimal lysis of the adjacent calvarium. Histology following complete excision confirmed the results obtained on the initial endoscopic biopsy. The final diagnosis was smooth muscle hamartoma.

Liver Lobe Torsion in a Guinea Pig (Cavia porcellus).

A 5-year-old, female intact guinea pig (Cavia porcellus) presented for acute inappetence. The abdomen was severely distended and tympanic with moderate discomfort. Radiographs showed gastric distension and displacement. Gastric dilatation and volvulus were suspected. At necropsy, the left lateral liver lobe was torsed at the hilus and infarcted. Histopathology showed regionally extensive coagulative necrosis and markedly congested sinusoids, causing marked hepatic cord atrophy and dissociation. Final diagnoses were severe gastric dilatation with left lateral liver lobe torsion (LLT) and regionally extensive liver infarction, and hemoabdomen. Reports of LLT in guinea pigs are likely underrepresented in the literature. LLTs should be considered in guinea pigs presenting for acute inappetence and abdominal distension. Laboratory tests and abdominal ultrasound can help differentiate LLT from other gastrointestinal pathologies seen in guinea pigs, such as gastric dilatation and volvulus. Early recognition of LLT in guinea pigs could potentially improve patient outcomes. This is the first published report of LLT in a guinea pig.