Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores.

The glycosaminoglycan hyaluronan (HA) plays important roles in diverse physiological functions where the distribution of its molecular weight (MW) can influence its behavior and is known to change in response to disease conditions. During inflammation, HA undergoes a covalent modification in which heavy chain subunits of the inter-alpha-inhibitor family of proteins are transferred to its structure, forming heavy chain-HA (HC•HA) complexes. While limited assessments of HC•HA have been performed previously, determining the size distribution of its HA component remains a challenge. Here, we describe a selective method for extracting HC•HA from mixtures that yields material amenable to MW analysis with a solid-state nanopore sensor. After demonstrating the approach in vitro, we validate extraction of HC•HA from osteoarthritic human synovial fluid as a model complex biological matrix. Finally, we apply our technique to pathophysiology by measuring the size distributions of HC•HA and total HA in an equine model of synovitis.

The effect of cyanoacrylate on knot elongation in three sutures used for prosthetic laryngoplasty in the horse.

OBJECTIVE: This study investigated the elongation following cyclic loading on square knots of 5 USP multifilament long-chain ultra-high molecular weight polyethylene core (UHMWPE), 2 mm woven UHMWPE tape, and 5 USP braided polyester, with and without cyanoacrylate glue. STUDY DESIGN: Experimental study. SAMPLE POPULATION: n = 4. METHODS: Three conditions (suture without knot, suture with knot, suture with knot + cyanoacrylate) were evaluated for each suture material on a mechanical test stand by measuring the increased length of the construct after cycling from 25 to 50N for 1000 repetitions at 20 mm/second. Knot elongation was determined by subtracting the length of the control suture from the suture with knot or suture with knot + cyanoacrylate. The data were analyzed with a linear regression model with robust estimation of variance. Post-hoc analysis determined the model adjusted differences (square knot vs. cyanoacrylate) as a difference from control. t-tests were conducted to identify the significant findings. RESULTS: Total elongation of polyester (6.2-7.8 mm) was greater than multifilament UHMWPE (3.4-6.4 mm) and UHMWPE tape (2-3.7 mm) for all conditions. Polyester had the lowest knot elongation (1.6 mm) and the addition of cyanoacrylate decreased knot elongation for polyester by 1 mm. CONCLUSIONS: Polyester had the most total construct elongation followed by multifilament UHMWPE and UHMWPE tape. Polyester showed the least knot elongation and cyanoacrylate decreased this knot elongation. CLINICAL SIGNIFICANCE: Total construct and knot elongation should be considered as contributing factors to loss of arytenoid abduction following prosthetic laryngoplasty when using polyester, multifilament UHMWPE, or UHMWPE tape. Addition of cyanoacrylate to polyester knots should be explored to limit elongation.

Comparison of cervical epidural morphine with intravenous morphine administration on antinociception in adult horses using thermal threshold testing.

OBJECTIVE: To compare the antinociceptive effects of morphine administered via cervical epidural catheter to intravenously administered morphine using a thermal threshold (TT) testing model in healthy adult horses. STUDY DESIGN: Prospective, randomized, blinded experimental study. ANIMALS: A total of six university-owned adult horses. METHODS: Horses were instrumented with a cervical (C1-C2) epidural catheter and TT testing device with probes at withers and thoracic limb coronary bands. All horses underwent three TT testing cycles including cervical epidural morphine administration (treatment EpiM; 0.1 mg kg-1), systemic morphine administration (treatment SystM; 0.1 mg kg-1) and no morphine administration (treatment Control). Baseline TT was established prior to treatments, and TT was tested at 15, 30, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480, 600 and 720 minutes following treatment. Horses underwent a 5 day washout period between treatments and the order of treatment was randomized. Differences between treatments were analyzed with repeated measures anova. RESULTS: Systemic and epidural morphine administration resulted in significantly higher TT values compared with baseline and control treatment. The duration of effect was significantly longer in treatment EpiM (10-12 hours) than in treatment SystM (1.5-2.0 hours). Horses in treatment EpiM had significantly higher TT values at time points 180-600 minutes (withers) and 300-600 minutes (coronary band) than horses in treatment SystM. CONCLUSIONS AND CLINICAL RELEVANCE: Cervical epidural administration of morphine provided antinociceptive effects as measured by increased TT for 10-12 hours compared with 1.5-2.0 hours for intravenously administered morphine. No complications or adverse effects were noticed following epidural placement of a C1-C2 catheter and administration of morphine. The use of a cervical epidural catheter can be considered for analgesia administration in treatment of thoracic limb and cervical pain in the horse.

Intratracheal oxygen administration increases FIO2 and PaO2 compared with intranasal administration in healthy, standing horses.

OBJECTIVE: To evaluate the efficacy of 2 different oxygen delivery strategies-intranasal and tracheal insufflation-on the inspired fraction of oxygen (FIO2) in standing horses and to determine the time needed for arterial oxygen partial pressure (PaO2) equilibration. ANIMALS: 6 healthy adult horses. PROCEDURES: In this blinded, randomized crossover design study, horses were randomly assigned to receive oxygen via nasal cannula (group N) or transcutaneous tracheal catheter (group T). After placement of venous and arterial catheters, FIO2 was measured through a catheter placed into the distal portion of the trachea. After baseline measurements were obtained, horses received oxygen at up to 25 mL/kg/min for 1 hour via either intranasal or intratracheal catheter. The FIO2 and PaO2 were recorded at 5, 10, 15, 20, 25, 30, 45, and 60 minutes during and 5, 10, 15, 20, and 30 minutes after oxygen insufflation. Data were analyzed by use of a 2-way repeated measures ANOVA with Tukey-Kramer post hoc testing for pairwise comparisons (P < 0.05). RESULTS: During oxygen administration, FIO2 and PaO2 increased significantly when compared with baseline, resulting in significantly higher values for group T (37.7 ± 2.4%; 214.6 ± 18 mm Hg) than for group N (34.3 ± 3.9%; 184.1 ± 11 mm Hg). The equilibration time was less than 10 minutes. CLINICAL RELEVANCE: Intratracheal oxygen administration resulted in better oxygenation than nasal insufflation and should therefore be considered in standing horses that are experiencing severe respiratory compromise. The equilibration between FIO2 and PaO2 is rapid in adult horses.

Cervical Epidural Spinal Analgesia for Acute Management of Severe Unilateral Forelimb Lameness: Case Report.

A 20-year-old Quarter Horse gelding was presented with severe right forelimb lameness (5/5 AAEP Lameness Scale) due to a tear of the superficial digital flexor muscle which was diagnosed via palpation of swelling and ultrasonography revealing major muscle fiber disruption and hematoma formation. When traditional systemic therapy (non-Steroidal anti-inflammatories) did not restore clinically acceptable comfort and the risk of supporting limb laminitis became a reasonable concern, a cervical epidural catheter was placed between the first and second cervical vertebrae in the standing, sedated patient using ultrasound guidance. The gelding was treated with epidural morphine (0.1 mg/kg every 24 h then decreased to 0.05 mg/kg every 12 h) and was pain-scored serially following treatment. Spinal analgesia was provided for 3 days. Pain scores significantly decreased following each treatment with morphine, and the gelding was successfully managed through the acutely painful period without any adverse effects associated with the C1-C2 epidural catheter placement technique, the epidural morphine, or contralateral limb laminitis. At the 2-month follow-up, the gelding was walking sound with no complications seen at the catheter insertion site. In this case, spinal analgesia using epidural morphine administered via a cervical epidural catheter was an effective and technically achievable option for pain management associated with severe forelimb muscle injury in a horse.

The surface stress of biomedical silicones is a stimulant of cellular response.

Silicones are commonly used for lubrication of syringes, encapsulation of medical devices, and fabrication of surgical implants. While silicones are generally viewed as relatively inert to the cellular milieu, they can mediate a variety of inflammatory responses and other deleterious effects, but the mechanisms underlying the bioactivity of silicones remain unresolved. Here, we report that silicone liquids and gels have high surface stresses that can strongly resist deformation at cellular length scales. Biomedical silicones, including syringe lubricants and fillings from FDA-approved breast implants, readily adsorb matrix proteins and activate canonical rigidity sensing pathways through their surface stresses. In 3D culture models, liquid silicone droplets support robust cellular adhesion and the formation of multinucleated monocyte-derived cell masses that recapitulate phenotypic aspects of granuloma formation in the foreign body response. Together, our findings implicate surface stress as a cellular stimulant that should be considered in application of silicones for biomedical purposes.