Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I

The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism. RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its absence in budding yeast has been associated with the accumulation of deletions within short tandem repeats. Here, we demonstrate that rNMP-associated deletion formation requires the activity of Top1, a topoisomerase that relaxes supercoils by reversibly nicking duplex DNA. The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease.     

Intravenous regional anesthesia in isoflurane anesthetized cats: lidocaine plasma concentrations and cardiovascular effects

Objective To determine if intravenous regional anesthesia (IVRA) can be used in cats without resulting in excessive plasma lidocaine concentrations or adverse cardiovascular effects. Study design Prospective, blinded crossover study. Animals Seven healthy male young adult cats weighing 3.96 ± 0.63 kg. Methods At 2.3% end‐tidal isoflurane concentration, lidocaine (L) 3 mg kg^?1 (1%) or saline (S) was injected in a distal cephalic venous catheter after application of two tourniquets to that forelimb which remained in place for 20 minutes. Heart and respiratory rates, arterial blood pressures and ECG were recorded every 5 minutes during tourniquet application and for 20 minutes following tourniquet removal. Lidocaine plasma concentrations were measured 5 minutes after injection and 0.5, 1, 2, 4, 8, 20 and 40 minutes after tourniquet removal. End tidal isoflurane concentrations were reduced to 1.5–2.0% to elicit a response to toe pinch (RTP) in the contralateral leg. The study was repeated similarly in the contralateral leg and RTP was graded for 40 minutes. Response was also tested in the leg previously injected, the differences between the two scores determined and those differences compared between the L and S treatments. The data were analyzed using anova for repeated measures comparing values to baseline. Significance was set at p < 0.005 using the Bonferroni method for multiple comparisons. Results There were no significant differences in physiologic parameters at either isoflurane concentration. Differences in RTP were significantly larger in the lidocaine treatment. The highest mean lidocaine concentrations were measured 0.5 minutes after tourniquet removal after both injections and were 2.79 ± 1.05 and 3.10 ± 1.11 µg mL^?1. The highest individual plasma concentration was 6.46 µg mL^?1. Conclusion No adverse hemodynamic effects were evident after IVRA lidocaine in any cat. The lidocaine dose studied inhibited a RTP until 20 minutes after tourniquet removal. Lidocaine concentrations varied and were measurable prior to tourniquet removal. Clinical relevance IVRA may be a suitable technique for cats undergoing surgery of the distal limbs.     

Behavioral responses following eight anesthetic induction protocols in horses

Objective To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Study design Randomized prospective experimental study. Animals Eight horses, 5.5 ± 2.4 years (mean ± SD) of age, and weighing 505 ± 31 kg. Methods After xylazine pre‐medication, each of eight horses was anesthetized on four occasions using one of eight different anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg^?1; THIO 6 mg kg^?1 + PRO 0.5 mg kg^?1; THIO 4 mg kg^?1 + PRO 1 mg kg^?1; THIO 2 mg kg^?1 + PRO 1.5 mg kg^?1; KET 2 mg kg^?1; KET 1.5 mg kg^?1 + PRO 0.5 mg kg^?1; KET 1 mg kg^?1 + PRO 1 mg kg^?1; KET 0.5 mg kg^?1 + PRO 1.5 mg kg^?1. Quality of induction and recovery were scored from 1 (poor) to 5 (excellent), and time taken to achieve lateral recumbency, first movement, sternal recumbency, and standing were evaluated. Results Time taken to achieve lateral recumbency after drug administration differed significantly (p < 0.0001) among the various combinations, being shortest in horses receiving THIO‐8 (mean ± SD, 0.5 ± 0.3 minutes) and longest in horses receiving KET‐2 (1.4 ± 0.2 minutes). The best scores for induction quality were associated with KET‐1.5 + PRO‐0.5, and the worst scores for induction quality were associated with KET‐2, although the difference was not significant. Time to first movement varied significantly among drug protocols (p = 0.0133), being shortest in horses receiving KET‐2 (12.7 ± 3.6 minutes) and longest in horses receiving THIO‐8 (29.9 ± 1.5 minutes). Horses receiving THIO‐8 made the greatest number of attempts to attain sternal posture (6.5 ± 4.7) and to stand (1.6 ± 0.8). Horses in the THIO‐8 treatment also received the poorest recovery scores (3.3 ± 1.0 and 3.0 ± 0.7 for sternal and standing postures, respectively). The best recovery scores were associated with combinations comprised mainly of propofol. Conclusions Combining propofol with either ketamine or thiopental modifies behaviors associated with use of the individual drugs. Clinical relevance Quality of early anesthesia recovery in horses may be improved by some combinations of propofol with either thiopental or ketamine.     

Evaluation of cardiac rhythm in dogs treated with levamisole hydrochloride using 24-hour ambulatory electrocardiography

The objective of this study was to evaluate the electrocardiographic alterations in the cardiac rhythm in dogs treated with levamisole hydrochloride over a period of 24 hours. Thirty-six mixed-breed dogs, both male and female, all clinically healthy, were used in the experiment. The dogs were divided into 6 groups with 6 dogs in each group, according to dosage and route of administration. The Holter test was initiated immediately after the treatment, and was maintained for 24 hours. In the group treated with 10 mg/kg by way of subcutaneous injection, one of them showed ventricular premature complexes, sometimes isolated and other times in pairs, and ventricular tachycardia, concentrated mainly in the first hour after administration of the drug. In the group of 6 animals treated subcutaneously with 25mg/kg, four showed isolated ventricular premature complexes, ventricular bigeminy and trigeminy, mainly during the first 2 hours after administration of the drug. All the animals in the other groups showed sinus arrhythmia followed by sinus arrest. The disturbances in the cardiac rhythm observed in clinically healthy animals treated with levamisole hydrochloride, indicate that it is preferable to avoid subcutaneous administration of levamisole hydrochloride and that the oral administration of the drug should be done with caution.     

Comparison of a New Braid Fixation System to an Interlocking Intramedullary Nail for Tibial Osteotomy Repair in an Ovine Model

Objectives— To compare bone healing of tibial osteotomy repaired with Nitinol wire braid and hardened steel rods (Braid system) and polymethylmethacrylate bone cement with an interlocking intramedullary (IM) nail fixation in an ovine model.
Study Design— In vitro and in vivo experimental study.
Animals— Adult female sheep (n=22).
Methods— Using sheep tibia, a middiaphyseal transverse osteotomy was performed in the right tibia, which were then randomly assigned to the Braid system group or IM nail group (n=5). The left tibia were used as controls. The torsional properties of tibial constructs were compared. The study was repeated in vivo in 12 sheep and mechanical properties and bone healing were evaluated at 12 weeks.
Results— In vitro, there was no significant difference in torsional stiffness between the groups. In vivo, operative time for the Braid system group was significantly shorter than the IM nail group. At 12 weeks, there were no significant differences in maximum torque and torsional stiffness between IM nail and Braid system groups nor were there significant radiographic or histologic differences between the groups.
Conclusions— The Braid system might decrease operative time for repair of transverse middiaphyseal tibial fractures and result in similar bone healing at 12 weeks after surgery compared with an interlocking IM nail repair.
Clinical Relevance— A Nitinol Braid system may be a treatment option for transverse midshaft tibial fractures.     

Long-Term Efficacy of a Percutaneously Adjustable Hydraulic Urethral Sphincter for Treatment of Urinary Incontinence in Four Dogs

Objective— To evaluate the efficacy of a surgically placed, static hydraulic urethral sphincter (SHUS) for treatment of urethral sphincter mechanism incompetency (USMI).
Study Design— Prospective study.
Animals— Spayed female dogs (n=4) with acquired USMI.
Methods— Urinary incontinence was assessed using a subjective continence score before and after implantation of an SHUS on the proximal urethra via ventral median celiotomy. Dogs were assessed for urinary continence, urinary tract infections, and implant-associated complications for 30 months. Residual incontinence was treated with percutaneous inflation of the SHUS with sterile saline solution through a biocompatible subcutaneous administration port.
Results— At last follow-up (26–30 months after surgery), continence scores improved from a median preoperative score of 3/10 to a median postoperative score of 10. One dog developed wound drainage over the subcutaneously placed administration port but remained continent after port removal. Three occluders were percutaneously filled with additional saline (median, 0.18 mL; mean, 0.16 mL) to improve continence after surgery.
Conclusions— Application and adjustment of an SHUS provided sustained improvements in continence score in all dogs.
Clinical Relevance— In this pilot study, 3 of 4 dogs with hydraulic urethral sphincter implantation had successful percutaneous adjustment and maintained improved continence scores for 2 years after surgery. Continence was maintained in the 4th dog even after administration port removal. Based on this pilot study, the SHUS warrants further clinical evaluation for treatment of dogs with USMI unresponsive to medical management.     

Survey of Feeding Practices, Supplement Use, and Knowledge of Equine Nutrition among a Subpopulation of Horse Owners in New England

Nutrition is a critical component of equine health. Horse owners' knowledge of nutrition is likely to affect their feeding practices. The aim of this study was to survey feeding practices, dietary supplement use, and knowledge about equine nutrition in New England by surveying a subpopulation of horse owners (67/337 or 19.8%) who brought their horses to the Large Animal Hospital at the Cummings School of Veterinary Medicine at Tufts University between July and September 2008. All owners reported feeding hay, with the majority feeding grass or timothy hay. Most owners (96%) reported feeding a concentrate in addition to hay. Approximately 84% of owners reported including at least one dietary supplement in their horse's daily feeding. The most commonly used supplements were chondroprotectives, electrolytes, and multivitamins. Survey questions designed to assess the owner's knowledge of nutrition suggested that many owners may not have a basic understanding of principles of equine nutrition; less than 50% knew the daily water and hay requirements for a horse, and 69% lacked knowledge about the proper use of concentrates in a diet. Most of the surveyed owners consulted multiple sources of information concerning equine nutrition, including veterinarians (n = 36), trainers (n = 27), feed stores (n = 10), and the internet (n = 7). Although the major source of information was the veterinarian, it appears that the communication between horse owners and their veterinarian about optimal feeding practices could be enhanced. This survey demonstrated areas in the veterinarian–client dialog that need to be addressed when evaluating the health and well-being of the horse.     

Adenosquamous Carcinoma of the Trachea in a Domestic Ferret (Mustela putorius furo)

A 4-year-old, castrated, male domestic ferret (Mustela putorius furo) was evaluated for a possible upper respiratory tract infection and wheezing for approximately 3 weeks. Supportive care for a suspected upper respiratory tract infection was initiated; however, the patient became progressively more dyspneic over the next 48 hours. A possible tracheal mass was identified upon thoracic radiographic imaging of the ferret. Tracheoscopy and a computed tomography scan of the neck and thorax confirmed the presence of a tracheal mass approximately 3 cm from the larynx obstructing 80% of the tracheal lumen. Rather than pursuing surgical resection, the owners elected humane euthanasia. An adenosquamous carcinoma of the trachea was diagnosed after histologic analysis. This tumor type has been diagnosed in the lungs of ferrets that were experimentally exposed to carcinogens found in cigarette smoke; however, there are no previous reports of this or any other tumor type associated with the ferret trachea. A tracheal mass causing a partial upper airway obstruction should be considered within the differential disease diagnosis list when a ferret is presented with dyspnea.