Cyclosporin: applications in small animal dermatology

Abstract Cyclosporin has been increasingly used for the treatment of skin diseases in small animals. Reported uses include the treatment of atopy, cutaneous lupus erythematosus, feline acquired alopecia resembling pseudopelade of humans, pemphigus erythematosus, pemphigus foliaceus, perianal fistulae and sebaceous adenitis. In addition, cyclosporin has been used anecdotally for several other skin diseases. Few side effects have been noted at doses therapeutic for dermatologic diseases. Current suggestions for monitoring, and the value of trough cyclosporin serum concentrations for prediction of toxicity and efficacy are discussed.     

Antegrade pyelography for suspected ureteral obstruction in cats: 11 cases (1995-2001)

OBJECTIVE: o determine sensitivity and specificity of radiography, ultrasonography, and antegrade pyelography for detection of ureteral obstructions in cats. DESIGN: Retrospective study. ANIMALS: 11 cats. PROCEDURE: Medical records of cats that had radiography, ultrasonography, and antegrade pyelography performed for suspected ureteral obstructions were examined. Ultrasound-guided pyelocentesis and fluoroscopic-assisted antegrade pyelography were performed on 18 kidneys in 11 cats. Obstructive ureteral lesions were confirmed in all cats by surgical or necropsy examination. Sensitivity and specificity of survey radiography, ultrasonography, and antegrade pyelography for identification of ureteral obstructions were calculated. Surgical or necropsy findings were used as the standard for comparison. RESULTS: All cats were azotemic. Mean +/- SD serum creatinine and BUN concentrations were 10.2 +/- 6.1 and 149 +/- 82 mg/dL, respectively. Fifteen of 18 ureters were found to be obstructed at surgery or necropsy. Sensitivity and specificity were 60 and 100% for radiography and 100 and 33% for ultrasonography, respectively, in identification of ureteral obstructions. Leakage of contrast material developed in 8 of 18 kidneys during antegrade pyelography and prevented diagnostic interpretation in 5 of 18 studies. For the 13 diagnostic studies, specificity and sensitivity were 100% by use of the antegrade pyelography technique. Correct identification of the anatomic location of the ureteral obstruction was obtained in 100% of diagnostic antegrade pyelography studies and in 60% of radiography or ultrasonography studies. CONCLUSIONS AND CLINICAL RELEVANCE: Antegrade pyelography can be a useful alternative in the diagnosis and localization of ureteral obstructions in azotemic cats, although leakage of contrast material may prevent interpretation of the study.     

Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis

OBJECTIVE: To examine in vitro effects of various antiproteolytic compounds on activity of matrix metalloproteinase (MMP)-2 and -9 in the tear film of horses with active corneal ulcers. SAMPLE POPULATION: Samples of tear film obtained from the eyes of 34 horses with active ulcerative keratitis. PROCEDURE: Horses were sedated, and tear samples were collected from the lower fornix of 34 ulcerated eyes by use of capillary tubes. The protease inhibitors 0.2% EDTA, 0.1% doxycycline, 10% N-acetylcysteine (NAC), 0.1% solution of a modified dipeptide that contains hydroxamic acid (ie, ilomostat), 0.1% alpha1-proteinase inhibitor (PI), 0.5% alpha1-PI, and 100% fresh equine serum (ES) were used to treat pooled samples. Amount of latent and active MMP-2 and -9 was measured by optical density scanning of gelatin zymograms of treated and untreated tear samples. RESULTS: Pooled tear samples obtained from ulcerated eyes contained the latent and active forms of MMP-2 and -9. Compared with MMP activity in untreated samples, total MMP activity (sum of all bands detected) observed on the gelatin zymogram gels was reduced by 99.4% by EDTA, 96.3% by doxycycline, 98.8% by NAC, 98.9% by ilomostat, 52.4% by 0.1% alpha1-PI, 93.6% by 0.5% alpha1-PI, and 90.0% by ES. CONCLUSIONS AND CLINICAL RELEVANCE: We documented that EDTA, doxycycline, NAC, ilomostat, alpha1PI, and ES inhibited MMP activity in vitro. Because these compounds use different mechanisms to inhibit various families of proteases in the tear film of horses, a combination of these protease inhibitors may be beneficial for treatment of corneal ulcers in horses.     

The effect of topical tripeptide-copper complex on healing of ischemic open wounds

OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation, Redmond, WA) on healing in ischemic open wounds. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Twenty-four adult male Sprague-Dawley rats. METHODS: Rats were divided into 3 groups: topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and no treatment (control). Six-mm-diameter, full-thickness wounds were created within an ischemic bipedicle skin flap on the dorsum of each rat. Each day, for 13 days, wound margins were traced, and the TCC and TCC vehicle groups were treated topically. Tracings were scanned, and wound perimeter and area were calculated. On days 6, 10, and 13, selected wounds were biopsied and analyzed for tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMP) 2 and 9. RESULTS: A significant decrease in wound area was seen in the TCC group, but not the vehicle group, when compared with the control group on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC vehicle on days 3 and 9. On day 13, initial wound area had decreased by 64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the control group. On days 6, 10, and 13, TCC-treated wounds contained significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than control wounds. CONCLUSION: Topical TCC resulted in accelerated wound healing in ischemic open wounds. CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of ischemic open wounds in rats and may have an application for the treatment of chronic wounds in other species. Clinical evaluation of topical TCC is warranted.     

Circular external skeletal fixation stabilization of antebrachial and crural fractures in 25 dogs

Fracture stabilization using circular external skeletal fixation was evaluated in 14 dogs with antebrachial fractures and 11 dogs with crural fractures. Most dogs were consistently weight bearing on the stabilized limb by 3 days following surgery. Although all dogs developed minor wire/pin tract inflammation and eight dogs developed major wire/pin tract inflammation, postoperative lameness was not consistently associated with wire/pin tract complications. Fractures in 23 dogs achieved radiographic union (mean +/- standard deviation [SD], 61 +/- 21 days; median, 57 days) without additional surgery; two dogs required restabilization of their fractures with linear fixators. Twenty of the 21 owners that could be contacted felt their dog had no (n=15) or only a mild (n=5) intermittent lameness at the time of final, long-term (mean +/- SD, 37 +/- 17 months; median, 42 months) assessment.     

Effects of postoperative rehabilitation on limb function after cranial cruciate ligament repair in dogs

OBJECTIVE: To determine the effects of early postoperative rehabilitation on limb function in dogs after surgery for ruptured cranial cruciate ligament (RCCL). DESIGN: Prospective clinical study. ANIMALS: 51 client-owned dogs. PROCEDURE: Dogs weighing between 20 and 40 kg (44 to 88 lb) that had RCCL and medial meniscal injury were studied. After removal of the RCCL and complete medial meniscectomy, the stifle joint was stabilized by use of a lateral retinacular stabilization technique. Twenty-five dogs were included in a postoperative rehabilitation group, and 26 dogs were included in an exercise-restricted group. Limb function (peak vertical force [PVF] and vertical impulse [VI]) was determined before surgery and 6 months after surgery, using force platform gait analysis. RESULTS: Prior to surgery, mean PVF and VI in affected limbs were similar between groups. Six months after surgery, PVF and VI were significantly increased in dogs of both groups. However, PVF and VI in dogs in the rehabilitation group were significantly greater than those of dogs in the exercise-restricted group. At this time, differences in limb function (as measured by PVF and VI) between the repaired and normal limbs were not evident in dogs in the rehabilitation group. Conversely, limb function in the repaired limb of dogs in the exercise-restricted group was still significantly less than that of the normal limb. CONCLUSION AND CLINICAL RELEVANCE: Dogs that have surgery for RCCL and a torn medial meniscus benefit from postoperative rehabilitation; rehabilitation should be considered part of the postoperative management of these patients.     

Evaluation of ameroid ring constrictors for the management of single extrahepatic portosystemic shunts in cats: 23 cases (1996-2001)

OBJECTIVE: To document the signalment; history; clinical signs; clinicopathologic, diagnostic imaging, and surgical findings; perioperative complications; and long-term clinical results of ameroid ring constrictor (ARC) placement on single extrahepatic portosystemic shunts (PSS) in cats. DESIGN: Retrospective study. ANIMALS: 23 cats treated with an ARC on a single extrahepatic PSS. PROCEDURE: An ARC was placed surgically around the PSS. Portal pressure was measured prior to ARC placement, with complete temporary PSS occlusion, and after ARC placement. Cats were scheduled for recheck transcolonic portal scintigraphy 8 to 10 weeks after surgery. Follow-up information was obtained by telephone interview with the owners. RESULTS: An ARC was successfully placed in 22 of 23 cats. Intraoperative complications, consisting of PSS hemorrhage, occurred in 2 cats. Mean (+/- SD) portal pressure (n = 15) was 6.7+/-2.9 mm Hg before PSS manipulation, 18.6+/-7.7 mm Hg with complete temporary PSS occlusion, and 6.9+/-2.7 mm Hg after ARC placement. Postoperative complications developed in 77% (17 of 22) of cats after ARC placement, and included central blindness, hyperthermia, frantic behavior, and generalized motor seizures. Perioperative mortality rate was 4.3% (1 of 23). Persistent shunting was identified in 8 of 14 cats. Overall, 75% (15 of 20) of cats had an excellent long-term outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Placement of an ARC on single extrahepatic PSS in cats resulted in low surgical complication and perioperative mortality rates, but most cats did have substantial postoperative complications. Persistent shunting was common, although many cats with persistent shunting were clinically normal.     

Effect of immunosuppressive doses of cyclosporine on pancreatic beta cell function in pigs

OBJECTIVE: To evaluate whether immunosuppressive doses of cyclosporine (CsA) have an adverse effect on the liver, kidney, and pancreatic beta cells of pigs. ANIMALS: 8 juvenile 8-week-old Landrace X Large White crossbred pigs. PROCEDURE: CsA (100 to 140 mg/kg) was administered orally to euglycemic pigs to reach whole blood trough concentrations of approximately 1500 ng/mL. To determine pancreatic beta cell function, plasma C-peptide and insulin concentrations were measured in response to i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Effects on liver and kidney were determined by monitoring serum measurements of liver function and serum creatinine concentrations, respectively. RESULTS: Plasma concentrations of C-peptide were significantly lower in euglycemic CsA-treated pigs, compared with control pigs, following i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Furthermore, the glucose clearance rate was decreased in euglycemic CsA-treated pigs, compared with control pigs. Serum creatinine concentrations and 4 of 7 serum measurements of liver function were not adversely affected by CsA administration. Serum concentrations of bilirubin and albumin were significantly increased, and serum alanine aminotransferase activity was significantly decreased in CsA-treated pigs, compared with control pigs. Histologic evaluation of liver and kidney sections revealed no pathologic findings in CsA-treated or control pigs. CONCLUSIONS AND CLINICAL RELEVANCE: In our study, immunosuppressive doses of CsA caused an impairment of porcine pancreatic beta cell function, but did not have toxic effects on the kidney. However, on the basis of changes in serum bilirubin and albumin concentrations and alanine aminotransferase activity, subclinical toxic effects on the liver did occur when immunosuppressive doses of CsA were administered.