Pharmacokinetics and renal clearance of sulfamethazine, sulfamerazine, and sulfadiazine and their N4-acetyl and hydroxy metabolites in horses

Plasma disposition, protein binding, urinary recovery, and renal clearance of sulfamethazine (SMZ), sulfamerazine (SMR), and sulfadiazine (SDZ) and their N4-acetyl and hydroxy derivatives were studied in 4 horses in a crossover trial. The plasma concentration-time curves of the metabolites paralleled those of the parent drug in the elimination phase. Sulfamethazine and SMR were extensively metabolized. In plasma and urine, the main metabolite of the 3 sulfonamides tested was the 5-hydroxypyrimidine derivative, which was highly glucuronidated. Difference in elimination half-life of SMZ, SMR, and SDZ could be related to difference in metabolism and renal clearance values. Metabolism speeds drug elimination, producing compounds with higher renal clearance values than those of the parent drug. Methyl substitution in the pyrimidine side chain increased hydroxylation of the parent drug, but prolonged the persistence of the sulfonamides studied in the body. The high concentration of N4-acetyl and hydroxy metabolites of SMZ and SMR in plasma and urine decreased the potential antibacterial activity of the parent drugs. Sulfadiazine was less metabolized, and microbiologically determined SDZ concentrations in plasma and urine were slightly lower than those measured by high-performance liquid chromatography.     

Pathology of equine phycomycosis

The pathological findings in three cases of equine phycomycosis in Costa Rica are described. Two cutaneous (Pythium sp) and one nasal lesion (Conidiobolus) were observed.     

Cycad (zamia) poisoning in Australia

The Cycads belong to an ancient family of plants and were the cause of the first well documented plant poisoning in Australia when Captain Cook's men and their pigs were affected by eating them. Subsequent reports particularly by early explorers refer to toxicity of the seeds to man. One reason for this was the evidence that the natives ate them. Subsequent reports and experimental work established the toxicity to sheep and cattle. In sheep and cattle 2 syndromes occur, ataxia and liver damage. In cattle the former is the better known, the spinal cord lesion being mainly a demyelination of the sensory pathways. The liver damage is necrosis and fibrosis.     

Hyperammonemia associated with urethral obstruction in a dog

Hyperammonemia was documented in a 10-week-old male Lhasa Apso referred for urethral obstruction and rupture. Results of liver function tests were normal. Staphylococcus sp was isolated from urine. Anomalies of the portal vascular system and hepatic insufficiency are the most common causes of hyperammonemia in the dog. Hyperammonemia, however, in the absence of recognizable concurrent hepatic disease, also may result from urinary stasis and infection with urea-splitting organisms.     

Osteofascial Compartment Syndrome in the Dog

Experimentally induced osteofascial compartment syndrome (OFCS) has been reported in the craniolateral compartment of the canine crus. In this study, anatomic dissections and contrast radiographs were used to describe three additional osteofascial compartments in canine limbs. Experimental OFCS was produced in four different compartments, and caused muscle and nerve pathology in each. When compartment pressures were evaluated in traumatized animals, moderate elevations in compartment pressures were found. A compartment syndrome that developed in one dog was surgically decompressed, returning elevated pressures to a safe level.     

Estimating adrenal cortical function in dogs with ACTH.

The peripheral blood response to intramuscular injection of 10 units ACTH in dogs was investigated because no experimental evidence for the standardization of this procedure for clinical use was available. Following the injection of ACTH in sodium chloride solution, neutrophilia, monocytosis, eosinopenia, and lymphopenia occurred. With the exception of eosinopenia, the greatest change in the concentration of each cell type in peripheral blood occurred between 2 and 4 hours post injection. The maximum change in eosinophil numbers occurred between 4 and 6 hours post injection. When all cell types were considered, 4 hours post injection was the most suitable time to measure the cellular response in peripheral blood in dogs which respond to ACTH. The data indicate that change in the ratio of neutrophils to lymphocytes (N/L) prior to and at 2 to 4 hours after ACTH injection in normal dogs was a sensitive index of response and occured sooner than eosinopenia. The extent of change in the N/L ratio was such that accuracy in interpretation could be obtained by counting as few as 40 cells.     

Evaluation of reconstitution of immunodeficient mice by partially purified thymic extracts.

Partially purified thymus products were used to evaluate the maturation of T lymphocytes in immunodeficient mice. Three different bovine thymic extracts, designated thymic extracts A, B, and C, were successful in increasing the longevity of conventionally raised nude mice. Daily injection of bovine thymic extracts A, B, and C and mouse thymus extracts failed to mature a population of T lymphocytes and restore the capacity to reject heart allografts. Preincubation of normal syngeneic bone marrow with thymic extract B in vitro before injection into nude mice also failed to reconstitute the host's ability to reject heart grafts. The number of antibody plaque-forming cells of sheep red blood cells in lethally irradiated, bone marrow-reconstituted mice could be increased by preincubating the bone marrow cells with bovine thymic extract fraction B before injection followed by daily injections. A similar but less marked increase in plaque-forming cells was obtained by the daily injection of bovine thymic extract fraction C. Complete functional maturation of T lymphocytes in immunodeficient animals appears to require more than thymic extract stimulation of bone marrow cells or pre-T lymphocytes.     

Nonneurogenic urinary incontinence in a canine female pseudohermaphrodite

Nonneurogenic incontinence was observed in a 1-year-old Pekingese X Poodle with female pseudohermaphroditism. The dog had male external genitalia as well as a well-developed vagina, uterus, and ovaries. Urinary incontinence was caused by an anomalous communication of the prostatic urethra with the vagina. Ovariohysterectomy and surgical correction of the urethrovaginal fistula was followed by remission of urinary incontinence. Subsequently, the dog developed estrogen responsive urinary incontinence. Nonneurogenic incontinence to be a common finding in canine pseudohermaphroditism associated with abnormalities of the vagina or urethra (or both). Surgical correction should be considered to correct anomalous communications between the genital and lower urinary tracts.     

Angiography of the crus penis in the ram and buck during erection

Serial angiography was used to determine blood flow patterns to the penis of rams and bucks. Animals were anesthetized and the internal pudendal artery was catheterized so that contrast medium could be injected toward the crus penis area. By comparing vascular patterns of the ram and buck during erection, it was found that flow patterns of the corpus cavernosum penis (CCP) and corpus spongiosum penis (CSP) were similar for both species. Contraction of the ischiocavernosus muscles occluded the arterial inflow and venous outflow to the CCP, making it a closed system during peak erection. However, during erection, the contrast medium continued to flow into the CSP, showing that it is not a closed system. In the vasodilatation phase, the CSP usually filled before and more intensely than did the CCP.