In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 alpha-subunits, in association with KCNE beta-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.

Non-steroidal anti-inflammatory drugs (NSAIDs) contribute to gastrointestinal ulcer formation by inhibiting epithelial cell migration and mucosal restitution; however, the drug-affected signaling pathways are poorly defined. We investigated whether NSAID inhibition of intestinal epithelial migration is associated with depletion of intracellular polyamines, depolarization of membrane potential (E m ) and altered surface expression of K + channels. Epithelial cell migration in response to the wounding of confluent IEC-6 and IEC-Cdx2 monolayers was reduced by indomethacin (100 μM), phenylbutazone (100 μM) and NS-398 (100 μM) but not by SC-560 (1 μM). NSAIDinhibition of intestinal cell migration was not associated with depletion of intracellular polyamines. Treatment of IEC-6 and IEC-Cdx2 cells with indomethacin, phenylbutazone and NS-398 induced significant depolarization of E m , whereas treatment with SC-560 had no effect on E m . The E m of IEC-Cdx2 cells was: −38.5±1.8 mV under control conditions; −35.9±1.6 mV after treatment with SC-560; −18.8±1.2 mV after treatment with indomethacin; and −23.7±1.4 mV after treatment with NS-398. Whereas SC-560 had no significant effects on the total cellular expression of K v 1.4 channel protein, indomethacin and NS-398 decreased not only the total cellular expression of K v 1.4, but also the cell surface expression of both K v 1.4 and K v 1.6 channel subunits in IEC-Cdx2. Both K v 1.4 and K v 1.6 channel proteins were immunoprecipitated by K v 1.4 antibody from IEC-Cdx2 lysates, indicating that these subunits co-assemble to form heteromeric K v channels. These results suggest that NSAID inhibition of epithelial cell migration is independent of polyamine-depletion, and is associated with depolarization of E m and decreased surface expression of heteromeric K v 1 channels.

Tenoscopy appears to be a useful modality in the treatment of open injury to the digital flexor tendon sheath in horses. Direct viewing, guided debridement, and targeted large-volume lavage are advantages obtained with intrathecal arthroscopy. Tenoscopy, when combined with antimicrobial and anti-inflammatory treatment, appears to offer a good chance of survival for affected horses.

Whereas in vivo testing is required, a bioabsorbable tendon plate may provide initial increased strength to support tendon healing and decrease external coaptation requirements.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively as therapeutic agents, despite their well documented gastrointestinal (GI) toxicity. At this time, the mechanisms responsible for NSAID-associated GI damage are incompletely understood. In this study, we used microarray analysis to generate a novel hypothesis about cellular mechanisms that underlie the GI toxicity of Accordingly, quantitative real-time reverse transcription polymerase chain reaction and immunoblotting were performed to assess the effects of NSAIDs on the expression of mRNA and protein for calpain 8, calpain 2, calpain 1, and calpastatin. In treated IEC-6 monolayers, NS-398 decreased the expression of mRNA for calpain 2 and calpain 8. Both NS-398 and indomethacin decreased the protein expression of calpains 8, 2, and 1. None of the NSAIDs affected expression of calpastatin mRNA or protein. The calpain inhibitors, N-acetyl-Leu-Leu-methioninal and N-acetyl-Leu-LeuNle-CHO, retarded IEC-6 cell migration in a concentration-dependant fashion, and these inhibitory effects were additive with those of indomethacin and NS-398. Our experimental results suggest that the altered expression of calpain proteins may contribute to the adverse effects of NSAIDs on intestinal epithelial restitution.Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively as therapeutic agents despite their well documented gastrointestinal (GI) toxicity. Adverse gastrointestinal effects of NSAIDs in humans and other species include oral, gastric, duodenal, and colonic ulceration (Lichtenberger, 2001;Tomisato et al., 2004). Despite exhaustive investigation, the mechanisms responsible for NSAID-associated GI damage are not completely understood. Evidence gathered to date suggests that NSAIDs may promote ulcer formation not only by inhibiting mucosal cyclooxygenase (COX) and decreasing cytoprotective prostaglandins (PGs) but also by adversely influencing intestinal microflora, neutrophil recruitment, surface hydrophobicity, and epithelial restitution (Lichtenberger, 2001;Little et al., 2007). Although the inhibition of COX isoforms has received much attention and investigation as the basis of GI

Background Peak reverse torque (PRT) is a valid method to evaluate implants’ secondary stability in the healing bone. The secondary stability is achieved by the implant over time and it has been positively correlated with the implants’ osseointegration level. In other words, peak reverse torque is the force required to break the bone-implant interface. The purpose of this study was to compare the peak reverse torque for the self-tapping and non-self-tapping screws used in a dynamic compression plate–screw–bone construct after 60 days of loading when used to stabilize 2.5-cm defects in the tibia of goats. The second objective was to compare the peak removal torque of the screws placed in the different positions to evaluate the impact of construct biomechanics on implants osseointegration. Results In total, 176 non-self-tapping screws and 66 self-tapping screws were used to fix the 8-holes dynamic compression plates to the bones. The screws were placed in the tibiae from proximal (position sites 1,2, 3) to distal (position sites 4,5,6) and were removed 60 days post-implantation. The animals remained weight-bearing throughout the study period. The screws placed in the proximal diaphysis had significantly less peak reverse torque than screws placed in the distal diaphysis in both groups ( p < 0.05). The peak reverse torque resistance was also significantly less for the non-self-tapping screws as compared with the self-tapping screws ( p < 0.05). The intracortical fractures in the trans-cortex occurred significantly more frequently during the placement of non-self-tapping screws ( p < 0.05) as compared with self-tapping screws ( p < 0.05). Conclusions Based on these results, we concluded that self-tapping screws may be expected to maintain a more stable bone-implant interface during the first 60 days of loading as compared with non-self-tapping screws. This should be a consideration for orthopedic surgeons and scientists using bone plates to stabilize non-load sharing fractures when a stable plate-screw-bone interface is needed to ensure prolonged stability.

Results suggest that horses with a complicated injury of the proximal, middle, or distal portion of the second or fourth metacarpal or metatarsal bone may be successfully treated by means of segmental ostectomy of the abnormal portion of the bone.

Results indicate that 8 weeks of enforced exercise after 7 weeks of joint immobilization did not restore joint function or values for various joint measurements determined prior to immobilization.