Objective—To determine the effect of short-term hyperinsulinemia on the localization and expression of endothelin receptor (ETR)-A and ETR-B in lamellar tissue of the forelimbs of horses. Samples—Distal portion of 15 cadaveric forelimbs from healthy adult horses (1 limb/horse) obtained immediately after slaughter at an abattoir. Procedures—Each forelimb was assigned to 1 of 3 treatment groups (perfused with autologous blood for 10 hours [control perfusion; n = 5], perfused with an insulin [142 ± 81 μU/mL] perfusate for 10 hours [insulinemic perfusion; 5], or not perfused [unperfused control; 5]). Immunohistochemical evaluation of lamellar tissue was performed to assess localization of ETR-A and ETR-B. Expression of ETR-A and ETR-B was measured semiquantitatively on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, and 3 = high-intensity staining) and quantitatively by means of gray value analysis with imaging software. Results—In all specimens, ETR-A and ETR-B were localized in endothelium, smooth muscle cells, axons, and keratinocytes. Quantitative expression of ETR-A in the midportion of the primary epidermal lamellae for the insulinemic perfusion group (149 ± 16) was lower than that for the control perfusion group (158 ± 15). Expression of ETR-B in the primary epidermal lamellae tips for the insulinemic perfusion group (140 ± 29) was higher than that for the control perfusion group (114 ± 8). Conclusions and Clinical Relevance—Hyperinsulinemia caused significant changes in endothelin receptor expression, which suggested that ETR antagonists might be beneficial for treatment of laminitis in horses.

Objective-To compare effects of 2 acetylcholinesterase inhibitors on recovery quality of horses anesthetized with isoflurane. Animals-6 horses in phase 1, 7 horses in phase 2A, and 14 horses in phase 2B. Procedures-The study comprised 3 phases (2 randomized, blinded crossover phases in horses undergoing orthopedic procedures and 1 prospective dose-determining phase). In phase 1, horses were anesthetized with isoflurane and received neostigmine or saline (0.9% NaCl) solution prior to anesthetic recovery. Phase 2A was a physostigmine dose-determining phase. In phase 2B, horses were anesthetized with isoflurane and received neostigmine or physostigmine prior to recovery. Objective recovery events were recorded and subjective visual analogue scale scores of recovery quality were assigned from video recordings. Results-Recovery measures in phase 1 were not different between horses receiving neostigmine or saline solution. In phase 2A, 0.04 mg of physostigmine/kg was the highest cumulative dose that did not cause clinically relevant adverse behavioral or gastrointestinal effects. Horses receiving physostigmine had higher mean +/- SD visual analogue scale recovery scores (70.8 +/- 13.3 mm) than did horses receiving neostigmine (62.4 +/- 12.8 mm) in phase 2B, with fewer attempts until sternal and standing recovery. Incidence of colic behavior did not differ among groups. Conclusions and Clinical Relevance-Inhibition with physostigmine improved anesthetic recovery quality in horses anesthetized with isoflurane, compared with recovery quality for horses receiving neostigmine. Inhibition of central muscarinic receptors by inhalation anesthetics may underlie emergence delirium in horses recovering from anesthesia.

Retinoids play an important role in lung development and immune response. The effects of retinoids are mediated through 2 families of retinoid receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs), with alpha (α), beta (β), and gamma (γ) subtypes in each family. To date, no data exist on the expression pattern of retinoid receptors in lungs of cattle, dogs, and pigs. Because of the biomedical importance of retinoid receptors in inflammation and immune responses, Western blot, immunohistology, and immunoelectron microscopy were used to determine the expression of retinoid receptors in normal lungs of cattle, dogs, and pigs (n = 2 for each species). Western blot showed expression of all 6 retinoid receptor subtypes in pig lungs. Immunohistology data indicated differential expression of retinoid receptors in airway epithelium, vascular endothelium, alveolar/septal macrophages, and alveolar septum in all 3 species. Electron microscopy showed nuclear localization of retinoid receptors in neutrophils and pulmonary intravascular macrophages. Retinoic acid receptors (RAR) α subtype were localized in cytoplasmic vacuoles of pig monocytes. These data indicate constitutive expression of retinoid receptors in the lungs of cattle, dogs, and pigs.

Objective-To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs. Sample-10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma. Procedures-Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis. Results-FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild. Conclusions and Clinical Relevance-This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.