Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus.

Mechanisms of anti-hantaviral activities of bovine lactoferrin (LF) and ribavirin (Rbv) were investigated. Hantavirus focus formation at 48 hr was 15% of the control in cells treated with 400 microg/ml LF for 1 hr at 37 degrees C prior to viral infection. Post infection treatment with 100 microg/ml Rbv also inhibited the focus formation to 2.5% of the control. Combined LF pre- and Rbv post-infection treatment completely inhibited focus formation. Viral glycoprotein (G2) and nucleocapsid protein (NP) syntheses were delayed in LF pretreated cells up to 24 hr post infection (hpi) but became comparable to the control by 48 hpi. Further, LF inhibited viral shedding at 24 hpi but did not inhibit shedding after 48 hpi. However, Rbv was able to inhibit synthesis of viral proteins, (+) and (-) strand RNAs also inhibited viral shedding after 24 hr. These results suggest that LF inhibits viral adsorption to cells, while Rbv inhibits viral RNA synthesis. For in vivo trials of LF and Rbv, LF pre- and Rbv post-treatment were evaluated in suckling mice infected with hantavirus, of which 7% survived. LF concentrations of 40 and 160 mg/kg administered prior to viral challenge improved survival rates to 15% and 70%, respectively for single administration and 85% and 94%, respectively, for double administration. Rbv concentrations of 25 and 50 mg/kg gave survival rates of 68% and 81%, respectively. This suggests that both LF and Rbv are efficacious in hantavirus infection in vivo.     

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.     

Ganglioneuroma in the small intestine of a juvenile pig

A mass was located in the small intestine of a slaughtered 6-month-old male Landrace-cross pig that had no clinical abnormalities. This egg-shaped well-circumscribed mass was situated in the submucosal and muscular tissue layers and protruded into the lumen. Histopathologically, the tumor comprised discrete or aggregated ganglion and schwannian cells in neuropil-like tissue. Some ganglion cells contained Nissl substance in their cytoplasm. The ganglion cells stained positive for neuron-specific enolase, class III β-tubulin, neurofilament, and synaptophysin; the schwannian cells stained positive for vimentin, S-100 protein, and glial fibrillary acidic protein. The tumor was diagnosed as a ganglioneuroma in accordance with these findings. Here, we have reported detailed immunohistochemical findings in addition to the histopathological features of a swine ganglioneuroma.     

Comparison of three commercially available prescription diet regimens on short-term post-prandial serum glucose and insulin concentrations in healthy cats

Dietary therapy is an important treatment component for diabetes mellitus (DM). In this study, the impact of three different commercially available diet regiments (1 general use and 2 aimed for treating obesity and DM) on short-term post-prandial serum glucose and insulin concentrations of five healthy cats to better understand what impact each of these diets may have for diabetic cats. The diet regiments used in this study were as follows: C/D dry (General Use- Low protein, High fat, High carbohydrate, and Low fiber), M/D dry (DM- High protein, High fat, Low carbohydrate, and High Fiber), and W/D dry (DM- Low Protein, Low Fat, High Carbohydrate, and High Fiber). No significant difference in post-prandial serum glucose levels were observed with the C/D (84.6 ± 1.5 mg/dl) and W/D (83.8 ± 1.4 mg/dl) dry diets when compared to pre-prandial fasting levels (83.9 ± 1.4 mg/dl). However, a significant reduction was observed with the M/D diet (78.9 ± 0.8 mg/dl) which had 50-60% less carbohydrates than either C/D or W/D diet. Unlike what was observed with post-prandial glucose levels, an interesting pattern emerged with post-prandial insulin levels, which were increasing with W/D, C/D, and M/D diets in that order (1.1 ± 0.2, 1.7 ± 0.2, and 2.3 ± 0.2 ng/ml respectively). Most surprising, though, was the fact that the W/D diet did not seem to stimulate insulin secretion as compared to pre-prandial levels (1.1 ± 0.1 ng/ml) in healthy cats. Interestingly, the W/D diet had high levels of carbohydrate and low levels of protein. Coincidentally, the only diet (M/D) which had a significant reduction in post-prandial glucose also showed the highest increase in post-prandial insulin in healthy cats. Therefore, dietary amounts of carbohydrate, fat, protein and fiber can all have an individual impact on post-prandial glycemia and subsequent insulin requirement levels. Just as concepts regarding dietary management of people with DM are evolving, investigators are reassessing what constitutes the ideal diet for the diabetic feline. As such, having a better understanding for each dietary component, may lead us to better understand how we can synergize certain dietary components to aid in DM management.     

Assessing the immune state of dogs suffering from pituitary gland dependent hyperadrenocorticism by determining changes in peripheral lymphocyte subsets

In order to evaluate the immune state of dogs suffering from pituitary-dependent hyperadrenocorticism (PDH), peripheral lymphocyte subsets were examined. Twenty seven PDH dogs and eight healthy control dogs were used in the current study. Eight healthy dogs served as the control group. Twenty seven PDH dogs were categorized into 4 groups based on their post serum cortisol concentrations by ACTH stimulation test: 2−5, excellent control (n = 8); 5−20, fair control (n = 7); >20, poor control (n = 4); and untreated (n = 8). Cell counts were executed with white blood cells (WBC), lymphocytes, CD3⁺ (T lymphocytes), CD4⁺ (Helper T lymphocytes), CD8⁺ (Cytotoxic T lymphocytes), CD21⁺ (B lymphocytes) cells in addition to calculating CD4⁺/CD8⁺ ratio. Results indicated a significant difference in lymphocyte numbers and lymphocyte subset populations (CD3⁺, CD4⁺, CD8⁺, and CD21⁺ cells) between PDH and control dogs. Moreover, comparison of the PDH groups (excellent control; fair control; poor control; untreated) demonstrated that all groups had a significant decrease in lymphocytes numbers (CD3⁺, CD4⁺ and CD21⁺ cell counts) as compared to control group. Meanwhile, no significant differences were observed in WBC counts and CD4⁺/CD8⁺ ratio between groups. Furthermore, lymphocyte subset distribution in excellent control PDH dogs without concurrent disease (n = 4) better resembled that of control dogs as compared to PDH dogs with concurrent disease (n = 4). PDH dogs may be suffering from an immuno-depressed state as evidenced by significant differences in lymphocyte subset populations. Furthermore, treatment of both PDH and concurrent disease might improve lymphocyte subset distribution.     

Detection of telomere length and oxidative stress in Chondrichthyes

Telomeres, repeating TTAGGG sequences at the ends of eukaryotic chromosomes, increase genomic stability. Telomere shortening occurs not only during DNA replication associated with cell division but also under oxidative stress, where reactive oxygen species damage DNA. Therefore, changes in telomere length can be used to evaluate chronic cost or stress responses incurred by individuals. The phylogenetically unique Chondrichthyes are among the least-studied groups of marine vertebrates. Telomere data are limited and have only been reported in a few Chondrichthyes species. In this study, we measured telomere length and quantified oxidative stress and antioxidant power in 17 Chondrichthyes species whose telomere length has not been measured before. The presence of telomere sequences?>?30 bp and lower values of oxidative stress were confirmed in most species. Average telomere length was not correlated with oxidative stress and antioxidant power in 15 species for which both measurements were available. It would be desirable in the future to elucidate the nature of telomeres in Chondrichthyes, and their direct relationship with reactive oxygen species.

     

The Intravenous Xylitol Tolerance Test in Non-Lactating Cattle

Xylitol is a five-carbon sugar alcohol that is often used for treatment of ketosis in dairy cattle in Japan. An intravenous xylitol tolerance test (IVXTT, 0.1 g/kg, bolus injection through the jugular vein) was performed in 4 non-lactating cows (n = 4) and the results were compared with those of an intravenous glucose tolerance test (IVGTT) performed under equivalent conditions. The serum xylitol concentration reached a peak value (41.4±9.0 mg/dl) at 5 min, and then rapidly decreased and almost disappeared within 2 h. The C ₀ for xylitol was 56.9±16.6 mg/dl and the t _1/2was 8.5±0.9 min. The administration of xylitol appeared to cause similar secretion of insulin to that caused by glucose. There was also a reduction in the concentration of free fatty acids. It seems that xylitol has value for the treatment of ketosis. However, rapid administration of xylitol appeared to have an osmotic diuretic action and might be a cause of dehydration.     

Changes in activities of enzymes related to energy metabolism in peripheral leukocytes of diabetic dogs with glycemic control by intensive insulin treatment

Changes in plasma glucose, immunoreactive insulin (IRI), and free fatty acids (FFA) concentrations and activities of enzymes related to energy metabolism in peripheral leukocytes were measured in type 1 diabetic dogs induced by streptozotocin administration before and after intensive insulin treatments. Before the insulin treatment, the plasma glucose concentrations were over 16.7 mmol/L and the activities of enzymes remarkably decreased in leukocytes of the diabetic dogs. In particular, malate dehydrogenase (MDH) activities decreased significantly. After glycemic control was achieved by insulin treatment, the plasma glucose concentrations were maintained between 6.8 and 7.7 mmol/L and the activities of enzymes restored to those in the control dogs. The changes in ML ratio (cytosolic MDH/lactate dehydrogenase specific activity ratio) reflected faithfully to metabolic conditions of animals and were considered to be a useful parameter to evaluate glycemic control and the effect of injected insulin in the diabetic dogs.     

Comparison of time-action profiles of insulin Glargine and NPH insulin in normal and diabetic dogs

Intermediate insulin injections are commonly used for glycemic control in insulin dependent diabetic dogs acting as a replacement for natural insulin. Neutral Protamin Hagedorn (NPH) insulin and insulin glargine are two types of injectable insulin preparations commonly used in humans. In our study, we investigated the time-action profiles of both aforementioned insulin preparations in normal dogs in order to determine whether co-administration of NPH and glargine would be of benefit to insulin dependent diabetic dogs as it is for humans suffering from insulin dependent diabetes. Time-action profiles of NPH insulin and insulin glargine in normal dogs demonstrated a clear difference between both insulin preparations confirming that NPH insulin is an intermediate-acting preparation whereas insulin glargine is a long-lasting preparation. In addition, co-administration of NPH insulin and insulin glargine resulted in tight glycemic control as compared to NPH insulin alone in insulin dependent diabetic dogs. However, co-administration result in hypoglycemia at the dosages tested.     

A bolus infusion of xylitol solution in the treatment of cow ketosis does not cause a surge in insulin secretion

When a solution of xylitol was rapidly administered intravenously (bolus infusion) to healthy cattle or those with ketosis, different results were obtained. In healthy cattle, a temporary surge in insulin secretion was observed, whereas in ketotic cattle no such surge was found, but instead a moderate level of secretion continued for a lengthy period. No significant difference in the areas under the insulin curve (AUC) was found between healthy cattle and ketotic cattle up to 120 min after xylitol infusion. These results clearly demonstrated that a bolus infusion of xylitol solution in ketotic cattle does not cause a temporary surge in insulin secretion unlike in healthy animals, but rather results in a continuous, gradual rise in secretion.