Pharmacokinetics of quinidine sulfate in dairy cattle

Pharmacokinetic profile and therapeutic range of plasma quinidine concentration were determined in dairy Holstein cows. Plasma half-life of intravenous quinidine was 1.28 +/- 0.492 (0.41-1.65) hr. The pattern of plasma quinidine transition after oral administration varied greatly among individuals. Total body clearance was 58.7 +/- 24.49 ml/min/kg, although renal quinidine clearance was 0.76 +/- 0.441 ml/min/kg. Therefore, the involvement of some extrarenal organ as the main site of excretion was suspected. Seven cows, diagnosed as atrial fibrillation or ventricular premature contraction, were orally administered with quinidine at various dosages. They showed plasma concentration of 2.3 +/- 1.59 mg/l when therapeutic effect was observed. Clinical signs of intoxication were observed at plasma quinidine concentrations over 10 mg/l. These results suggest the difficulty with the maintenance of effective plasma quinidine concentration by an oral or a single intravenous administration, and thus it is concluded that use of quinidine for treatment arrhythmic cows must be carefully done in order to avoid possible intoxication.     

Glucose transport and glycolytic enzyme activities in erythrocytes of two-year-old thoroughbreds undergoing training exercise

d-Glucose transport and cytosolic enzyme activities were measured in erythrocytes from 2-year-old thoroughbreds under continuous training exercise (race horses) and compared with those from untrained horses of various ages (sires, mares and untrained 2-year-old thoroughbreds). The activities of the glucose transport and glycolytic enzymes, hexokinase and pyruvate kinase, in the race horses' erythrocytes were elevated to 2–3.5 times above those of untrained horses. There were no significant differences in plasma glucose, triglyceride or IRI concentrations between the horses in training and untrained horses. The increases in glucose transport and glycolytic enzyme activities in their erythrocytes are considered to reflect an increased metabolic activity in the race horses resulting from the training exercises.Abbreviations D-GT d-glucose transport - EDTA ethylenediaminetetraacetic acid - ELISA enzyme-linked immunosorbent assay - G6PD glucose-6-phosphate dehydrogenase - HK hexokinase - IRI immunoreactive insulin - PBS phosphate-buffered saline - PK pyruvate kinase     

Immunohistochemical detection of apolipoprotein A-I and B-100 in canine atherosclerotic lesions

We attempt to determine and compare the localization of apolipoproteins (apo) apoA-I and B-100 in atherosclerotic lesions of canine aortas, coronary arteries, and the peripheral arteries, using immunohistochemical techniques. Histopathologically, atherosclerotic lesions were characterized by deposition of lipids and infiltration of lipid-laden foamy cells in the tunica intima and tunica media, sometimes forming fibrofatty plaques containing abundant sudanophilic and mineralized material. Canine apoA (CapoA)-I and canine apoB (CapoB)-100 immunopositive signals were simultaneously observed in mild and severe atherosclerotic lesions of the aorta, coronary arteries, splenic arteries, and renal arteries in the double-immunolabeled sections. Both CapoA-I and CapoB-100 positive signals were seen in the cytoplasm of endothelial cells, smooth muscle cells, and macrophages. The subendothelial space and extracellular matrix in the tunica intima and media were also positive. Neither CapoA-I nor CapoB-100 positive signals were seen in normal arteries. These findings closely resemble those of the localization of apoA-I and apoB-100 in human atherosclerotic lesions.     

Changes in peripheral lymphocyte subsets in the type 1 diabetic dogs treated with insulin injections

Plasma metabolites and peripheral lymphocyte subsets were measured in ten diabetic and ten control dogs to investigate their significances as indicators to evaluate immune states in the diabetic dogs. Diabetic dogs were treated with insulin injections, however their plasma glucose and fructosamine concentrations were significantly higher than those of the controls. There were no significant differences in counts of total white blood cells (WBC) and lymphocyte CD8(+) cells (cytotoxic T cells) between the control and the diabetic dogs. In the diabetic dogs, the counts of CD3(+) (T cells), CD4(+) (Helper T cells) and CD21(+) (B cells) cells and the peripheral lymphocytes CD4/CD8 ratio were significantly lower than those in the control dogs. We confirmed abnormality of lymphocyte subsets in insulin treated diabetic dogs and it may relate to depression of immunocompetence and high susceptibility to common infectious diseases.     

Comparison of enzyme activities in plasma and leukocytes in dairy and beef cattle

Concentrations of plasma glucose, immunoreactive insulin (IRI) and free fatty acid (FFA) and activities of enzymes related to energy metabolism and lactate dehydrogenase (LDH) isoenzyme pattern in plasma and leukocytes were investigated in lactating Holstein cows (dairy cattle) and fattening Japanese Black Wagyu x Holstein steers (beef cattle). IRI concentrations and LDH and malate dehydrogenase (MDH) activities in the plasma of beef cattle were significantly higher than those in dairy cattle. The cytosolic ratio of MDH/LDH activity in the leukocytes of beef cattle was significantly higher than that of dairy cattle. These findings might be associated with the different energy metabolism between dairy and beef cattle.     

The canine prostate cancer cell line CHP‐1 shows over‐expression of the co‐chaperone small glutamine‐rich tetratricopeptide repeat‐containing protein α

Although androgen therapy resistance and poor clinical outcomes are seen in most canine prostate cancer cases, there are only a few tools for analysing canine prostate cancer by using a cell biological approach. Therefore, to evaluate androgen‐independent neoplastic cell growth, a new canine prostate cancer cell line (CHP‐1) was established in this study. CHP‐1 over‐expressed the co‐chaperone small glutamine‐rich tetratricopeptide repeat‐containing protein α (SGTA), which is over‐expressed in human androgen‐independent prostate cancer. The CHP‐1 xenograft also showed SGTA over‐expression. Although CHP‐1 shows poor androgen receptor (AR) signalling upon dihydrotestosterone stimulation, forced expression of AR enabled evaluation of AR signalling. Taken together, these results suggest that CHP‐1 will be a useful model for investigating the pathogenesis of androgen‐dependent and androgen‐independent canine prostate cancer.     

Activities of enzymes in some types of peripheral leucocytes may reflect the differences in nutrient metabolism between dogs and cats

Plasma metabolites and immunoreactive insulin (IRI) concentrations and enzyme activities of some types of peripheral leucocytes were measured to clarify one aspect of the differences in nutrient metabolism between dogs and cats. There were no significant differences in plasma concentrations of glucose, triglyceride, free fatty acids and IRI between dogs and cats. Higher total cholesterol and lower HDL cholesterol concentrations were observed in feline plasma, and H/T ratio (HDL/total cholesterol concentrations) was significantly lower than that in canine plasma. The cytosolic activities of fructokinase (FK), pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) were significantly higher and the activities of cytosolic malate dehydrogenase (MDH) and mitochondrial glutamate dehydrogenase (GLDH) were significantly lower in feline leucocytes than those in canine leucocytes. Higher activities of FK, PK and G6PD, which regulate the rate of biosynthesis of fatty acids, may reflect the different characteristics in nutrient metabolism in feline tissues from canine tissues.     

A new strain of Melon necrotic spot virus that is unable to systemically infect Cucumis melo

We report a new strain of Melon necrotic spot virus (MNSV) that is unable to systemically infect Cucumis melo. A spherical virus (W-isolate), about 30 nm in diameter like a carmovirus, was isolated from watermelons with necrotic symptoms. The W-isolate had little serological similarity to MNSV, and it did not cause any symptoms in six melon cultivars susceptible to MNSV; however, the host range of the W-isolate was limited exclusively to cucurbitaceous plants, and transmission by O. bornovanus was confirmed. Its genomic structure was identical to that of MNSV, and its p89 protein and coat protein (CP) showed 81.6 to 83.2% and 74.1 to 75.1% identity to those of MNSV, respectively. Analysis of protoplast showed that the W-isolate replicated in melons at the single-cell level. Furthermore, chimeric clones carrying the CP of MNSV induced necrotic spots in melons. These results suggested that the absence of symptoms in melons was due to a lack of ability of the W-isolate to move from cell to cell. In view of these findings, we propose that the new isolate should be classified as a novel MNSV watermelon strain.     

Time-action profiles of insulin detemir in normal and diabetic dogs

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2 h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8–10 h while the glucose-lowering effect lasted for over 24 h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.