Examination of the effect of a naturally occurring mutation in glycoprotein L on Marek's disease virus pathogenesis

We recently reported a comparison of glycoprotein-encoding genes of different Marek's disease virus pathotypes (MDVs). One mutation found predominantly in very virulent (vv)+MDVs was a 12-bp (four-amino acid) deletion in the glycoprotein L (gL)-encoding gene in four of 23 MDV strains examined (three were vv+MDVs and one was a vvMDV). This mutation was noted in the gL of the TK (615K) strain, but not in the RL (615J) strain of MDV. These strains have identical mutations in the meq gene characteristic of vv+MDVs but can be distinguished by the mutation in the gL-encoding gene. The TK strain was originally isolated from vaccinated chickens and appeared to confer or enhance horizontal transmission of the vaccine virus, herpesvirus of turkeys (HVT). Because the molecular basis for increased virulence of MDV field strains is unknown, we hypothesized that one mechanism might be by coreplication of MDV-1 strains with HVT and that it could be mediated by the mutation of gL, an essential component of the glycoprotein H/L complex. In this study, we compared the pathogenicity of TK (615K) and RL (615J) strains of MDV in the presence and absence of simultaneous HVT coinfection. MDV infections were monitored at the levels of viremia (for both MDV-1 and HVT), clinical signs of MD, tumor incidence, and mortality in 1) inoculated chickens, 2) chickens exposed at 1 day of age, 3) chickens exposed at 2 wk of age, and 4) chickens exposed to both TK/HVT- and RL/HVT-infected chickens at 6 wk of age. We found high incidences of clinical MD signs in all inoculated treatment groups and all chickens exposed to TK and RL viruses, regardless of the presence of HVT. The median time to death of chickens exposed to TK1HVT-infected chickens, however, was lower than the other treatment groups for contact-exposed chickens. Although this difference was not considered to be statistically significant to a rigorously interpreted degree because of the removal of chickens for sampling from the test groups, these data suggest that replication of the TK strain and HVT, when coadministered, might incrementally affect the virulence of MDV-1 strains. The strict correlation of this enhancement of virulence with the mutation in gL, however, requires additional experiments with genetically identical MDV background strains.     

Modulation of canine immunosenescence by life-long caloric restriction

Caloric restriction (CR) has been shown to retard immunosenescence and to extend median and maximum life span in rodent species. Longitudinal effects of CR on the canine immune system are presented in this report. A group of 48 Labrador Retrievers, divided at weaning into weight- and sex-matched pairs, were maintained on a diet restriction protocol from age 8 weeks until death. Each restricted dog received 75% of the total food consumed by its control-fed pair mate. Immune parameters were monitored from 4 to 13 years. CR retarded age-related declines in both lymphoproliferative responses and absolute numbers of lymphocytes and the T, CD4, and CD8-cell subsets. In females, CR attenuated the age-related increase in T-cell percentages and marginally retarded the age-related increase in memory cell percentages. Age-related changes in B-cell percentages and numbers were augmented by CR. No direct effect of CR on phagocytic activity of PMN, antibody production or NK cell activity, was observed. Lower lymphoproliferative responses, lower numbers of lymphocytes, T, CD4 and CD8 cells, lower CD8 percentages and higher B-cell percentages were all found to be significantly associated with a decreased likelihood of survival in these dogs.     

MAGNETIC RESONANCE IMAGING OF A MEDULLARY DERMOID CYST WITH SECONDARY HYDROCEPHALUS IN A DOG

Magnetic resonance images were acquired of the brain of a 7-year-old male Golden Retriever with hydrocephalus secondary to a medullary lesion. Images were acquired prior to and 4 weeks following surgical treatment for the hydrocephalus, and the dog was euthanased following the second imaging session. The MR images demonstrated a medullary lesion with patchy but predominantly hyperintense signal with both T1- and T2-weighting, within which small areas of low signal were scattered. There was little edema associated with this lesion and no enhancement with gadolinium. Postmortem examination revealed the medullary mass to be a dermoid cyst. Several small nodular lesions were identified within the central nervous system on the magnetic resonance images whose origin was uncertain on postmortem examination.     

Effects of sulfamethoxazole-trimethoprim on thyroid function in dogs

OBJECTIVE: To evaluate effects of trimethoprim-sulfamethoxazole (T/SMX) on thyroid function in dogs. ANIMALS: 6 healthy euthyroid dogs. PROCEDURE: Dogs were administered T/SMX (14.1 to 16 mg/kg, PO, q 12 h) for 3 weeks. Blood was collected weekly for 6 weeks for determination of total thyroxine (TT4), free thyroxine (fT4), and canine thyroid-stimulating hormone (cTSH) concentrations. Schirmer tear tests were performed weekly. Blood was collected for CBC prior to antimicrobial treatment and at 3 and 6 weeks. RESULTS: 5 dogs had serum TT4 concentrations equal to or less than the lower reference limit, and 4 dogs had serum fT4 less than the lower reference limit after 3 weeks of T/SMX administration; cTSH concentrations were greater than the upper reference limit in 4 dogs. All dogs had TT4 and fT4 concentrations greater than the lower reference limit after T/SMX administration was discontinued for 1 week, and cTSH concentrations were less than reference range after T/SMX administration was discontinued for 2 weeks. Two dogs developed decreased tear production, which returned to normal after discontinuing administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of T/SMX at a dosage of 14.1 to 16 mg/kg, PO, every 12 hours for 3 weeks caused decreased TT4 and fT4 concentrations and increased cTSH concentration, conditions that would be compatible with a diagnosis of hypothyroidism. Therefore, dogs should not have thyroid function evaluated while receiving this dosage of T/SMX for >2 weeks. These results are in contrast to those of a previous study of trimethoprim-sulfadiazine.     

Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs

The objective of this study was to evaluate the safety and efficacy of a purified porcine insulin zinc suspension for treating dogs with uncomplicated diabetes mellitus. Fifty-three dogs were treated for 60 days after an initial dose determination period. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs were determined before beginning insulin therapy (time 0), at the end of the dose determination period (time 1), 30 days after time 1 (time 2), and 60 days after time 1 (time 3). Presence of polyuria, polydipsia, and ketonuria was determined at each time point. Adequacy of control of hyperglycemia was based on 12-hour blood glucose curves and improvement in clinical variables (results of physical examinations, historic information, polyuria, polydipsia, and ketonuria). Safety was evaluated by questionnaire, performance of physical examination, CBC, serum chemistry profile, and urinalysis. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs at times 1, 2, and 3 were significantly lower compared with time 0 (P < .0001). There was a reduction in the proportion of dogs with polyuria, polydipsia, and ketonuria of 82, 86, and 80%, respectively. All of the dogs had adequate glycemic control at time 1, 66% at time 2, and 75% at time 3. At time 3, 66% of dogs required insulin injections q12h. Other than hypoglycemia, there were no important adverse effects of insulin administration. The insulin, was safe and efficacious for reducing blood glucose and clinical signs in dogs with diabetes mellitus.     

Management of ureteral obstruction.

The most common cause of ureteral obstruction in dogs and cats is ureteral calculi. Common clinical signs associated with ureteral obstruction include abnormalities in urination, persistent urinary tract infection, abdominal pain, vomiting, anorexia, weight loss,and depression or lethargy. Medical management of ureteral obstruction includes fluid diuresis, muscle relaxants, and treatment of azotemia using nephrostomy tubes or hemodialysis. Surgical techniques used to restore patency to the ureter include ureterotomy,partial ureterectomy and ureteroneocystostomy, and ureteral resection and anastomosis. Lithotripsy has been used in dogs to remove ureteral calculi. Renal function can be preserved if complete ureteral obstruction is relieved within several days of onset.     

Extreme eosinophilia with disseminated eosinophilic granulomatous disease in a horse

Extreme eosinophilia with disseminated eosinophilic granulomatous disease is described in a 4-year-old Arabian mare. Clinical signs included weight loss, coughing, jugular distention, and ventral edema. Cutaneous lesions were not observed. Eosinophilic inflammation was observed in cytologic specimens from the respiratory tract, body cavities, and lymph nodes. At necropsy, a 20-cm diameter intrathoracic mass was observed. Smaller nodules were present in the lymph nodes, liver, spleen, adrenal glands, pancreas, and skeletal muscle. Histologically, these masses and nodules were characterized by infiltrates of eosinophils, macrophages, and multinucleated giant cells, reactive fibroplasia; and multifocal eosinophilic coagula. Microscopically, mild eosinophilic infiltrates were observed in sections of stomach, small intestine, colon, and pleura; however, gross lesions were not observed in these tissues at necropsy. The etiology of the extreme eosinophilia and disseminated eosinophilic granulomatous disease in this horse was not determined.