Evaluation of d,l-ethionine as a mechanism for pancreatic islet regeneration in dogs

Objective To determine whether induction of pancreatic necrosis and islet proliferation by d,l‐ethionine has potential for treating dogs with b ‐cell insufficiency. Design Eighteen mixed breed dogs of both sexes were given d,l‐ethionine at 100 mg/kg three times weekly for 2 weeks; 6 dogs were euthanased at 2, 14 and 28 d after the last dose. Methods Clinical signs during administration and recovery were assessed. Routine biochemical analyses were performed before each ethionine dose and then once weekly. Faecal samples were examined weekly for malassimilated nutrients and blood. Blood coagulation screening tests (OSPT and APTT) were determined on four dogs after ethionine administration. Intravenous glucose tolerance tests were conducted before the first and after the last ethionine dose and then fortnightly. All dogs were necropsied and pancreas, liver, kidney and jejunum were examined microscopically. Results During ethionine administration all animals displayed vomiting, inappetence, diarrhoea (often with blood), weight loss and depression. Three dogs were euthanased prematurely due to severe illness, but those allowed to recover were eating and brighter 7 d after cessation of ethio‐nine administration. Serum concentrations of TLI, amylase and lipase increased initially, then decreased, during administration but returned to normal during recovery. Concentrations of ALT, ALP, unconjugated and conjugated bilirubin increased during administration then decreased slowly. Histological examination revealed hepatic lipidosis and necrosis, but no renal or jejunal lesions. In most dogs, faecal examination demonstrated increased undigested starch and muscle, as well as increased digested and undigested fat, during ethio‐nine administration or early during the recovery period, suggesting transient malassimilation. APTT was unchanged but OSPT was prolonged in all dogs. There was no impairment of insulin secretion or glucose intolerance and C‐peptide concentrations were unaffected. Immediately after ethionine administration there was delayed insulin degradation and by day 43 there was evidence of increased insulin sensitivity. Conclusion d,l‐ethionine administration in dogs appeared not to interfere with insulin secretion, but caused clinical signs and laboratory changes indicative of pancreatic exocrine necrosis, severe hepatobiliary disease and transient malas‐similation. Pancreatic and hepatic dysfunction was severe but clinical recovery occurred after ethionine administration ceased. The severe side‐effects observed with d,l‐ethionine should preclude its potential use for treating diabetes mellitus in dogs.     

Effect of Se on selenoprotein activity and thyroid hormone metabolism in beef and dairy cows and calves

Although Se is essential for antioxidant and thyroid hormone function, factors influencing its requirement are not well understood. A survey and two experiments were conducted to determine the influence of cattle breed and age on selenoprotein activity and the effect of maternal Se supplementation on cow and calf selenoprotein activity and neonatal thyroid hormone production. In our survey, four cowherds of different ages representing three breeds were bled to determine the influence of breed and age on erythrocyte glutathione peroxidase activity (RBC GPX-1). All females were nonlactating, pregnant, and consumed total mixed diets (Holstein) or grazed pasture (Angus and Hereford). In our survey of beef breeds, yearlings had greater average RBC GPX-1 activity than mature cows. In Exp. 1, neonatal Holstein heifers (n = 8) were bled daily from 0 to 6 d of age to determine thyroid hormone profile. An injection of Se and vitamin E (BO-SE) was given after the initial bleeding. Thyroxine (T4) and triiodothyronine (T3) concentrations were greatest on d 0 and decreased (P < 0.05) continuously until d 5 postpartum (156.13 to 65.88 and 6.69 to 1.95 nmol/L, d 0 to 5 for T4 and T3, respectively). Reverse T3 concentrations were 3.1 nmol/L on d 0 and decreased (P < 0.05) to 0.52 nmol/ L by d 5. In Exp. 2, multiparous Hereford cows were drenched weekly with either a placebo containing 10 mL of double-deionized H2O (n = 14) or 20 mg of Se as sodium selenite (n = 13). After 2 mo of treatment, Se-drenched cows had greater (P < 0.01) plasma concentrations than control cows (84.92 vs. 67.08 ng/mL), and at parturition, they had plasma Se concentrations twofold greater than (P < 0.05) control cows (95.51 vs. 47.14 ng Se/mL). After 4 mo, cows receiving Se had greater (P < 0.05) RBC GPX-1 activity than controls; this trend continued until parturition. Colostrum Se concentration was twofold greater (P < 0.05) in Se-drenched cows than control cows (169.97 vs. 87.00 ng/mL). Calves born to cows drenched with Se had greater (P < 0.05) plasma Se concentration, RBC GPX-1, and plasma glutathione peroxidase activity on d 0 compared with calves born to control cows. By d 7, no differences in plasma glutathione peroxidase activity in calves were observed. Maternal Se supplementation did not influence calf thyroid hormone concentrations. Selenium provided by salt and forages is not adequate for cattle in Se-deficient states.     

Equine castration: review of anatomy, approaches, techniques and complications in normal, cryptorchid and monorchid horses

Complications associated with equine castration are the most common cause of malpractice claims against equine practitioners in North America. An understanding of the embryological development and surgical anatomy is essential to differentiate abnormal from normal structures and to minimise complications. Castration of the normal horse can be performed using sedation and regional anaesthesia while the horse is standing, or under general anaesthesia when it is recumbent. Castration of cryptorchid horses is best performed under general anaesthesia at a surgical facility. Techniques for castration include open, closed and half-closed techniques. Failure of left and right testicles to descend occurs with nearly equal frequency, however, the left testicle is found in the abdomen in 75% of cryptorchid horses compared to 42% of right testicles. Bilateral cryptorchid and monorchid horses are uncommon. Surgical approaches described for the castration of cryptorchid horses include an inguinal approach with or without retrieval of the scrotal ligament, a parainguinal approach, or less commonly a suprapubic paramedian or flank approach. Laparoscopic castration of cryptorchid horses has recently been described but the technique has limited application in practice at this time. A definitive diagnosis of monorchidism can only be made after surgical exploration of the abdomen, removal of the normal testis and hormonal testing. Hormonal assays reported to be useful include analysis of basal plasma or serum testosterone or oestrone sulphate concentrations, testosterone concentrations following hCG stimulation, and faecal oestrone sulphate concentrations. Reported complications of castration include postoperative swelling, excessive haemorrhage, eventration, funiculitis, peritonitis, hydrocele, penile damage and continued stallion-like behaviour.