Effect of Hot Water Bottles on Body Temperature during Magnetic Resonance Imaging in Dogs under General Anesthesia: A Retrospective Study.

Prevention of hypothermia induced by anesthesia and enhanced by low environmental temperatures is difficult in magnetic resonance imaging (MRI) examinations in dogs as forced warming devices, including magnetic materials, are not acceptable for use in the MRI room. A hot water bottle (HWB) can be carried into an MRI examination room and can contribute to the prevention or attenuation of hypothermia. Here, we retrospectively investigated the effects of HWB on body temperature during MRI examinations in dogs under general anesthesia (GA). From anesthesia records of the Veterinary Medical Teaching Hospital, Okayama University of Science, validated data of 100 dogs that underwent an MRI examination under GA were obtained and divided into the following two groups: one group received HWB, while the other did not. Decrease in rectal temperature 15 min after intubation was significantly smaller in the group using HWB than in the group without HWB. In conclusion, the use of hot water bottles might be one of the methods to attenuate hypothermia in the early period but should not be expected for complete prevention of hypothermia, and it was not recommendable necessarily for body temperature management during MRI examinations in dogs under general anesthesia.

Effects of Multimodal Analgesic Protocol, with Buprenorphine and Meloxicam, on Mice Well-Being: A Dose Finding Study.

The anesthetic or analgesic agent of choice, route and frequency of anesthetic or analgesic administration, and stressors induce distress during the perioperative period. We evaluated a multimodal analgesic protocol using buprenorphine and meloxicam on the well-being of mice. Twenty-four Slc:ICR male mice were divided into control, anesthesia + analgesia, and surgery + anesthesia + analgesia groups. Tap water (orally: PO) and water for injection (subcutaneous: SC) were administered to the control group. Buprenorphine was administered twice (SC, 0.1 mg/kg/8 h) and meloxicam was administered thrice (PO, 5 mg/kg/24 h) to the anesthesia + analgesia and surgery + anesthesia + analgesia groups. The mice were subjected to laparotomy and assessed for several parameters. Even in absence of surgical pain, the anesthesia + analgesia group presented the same negative effects as the surgery + anesthesia + analgesia group. This multimodal analgesic protocol for mice was expected to have an analgesic effect on pain associated with laparotomy but was not sufficient to prevent food intake and weight decrease. This does not negate the need to administer analgesics, but suggests the need to focus on and care not only about the approach to relieve pain associated with surgery, but also other types of distresses to minimize negative side effects that may interfere with postoperative recovery in mice.

Noninvasive Thermographic Photographing as an Assessment of the State of Discomfort in a Dog Receiving Radiation Therapy.

In humans, radiation induces dilation of capillaries and inflammatory reactions to raise skin temperature. Thermography is used to detect abnormalities after radiation therapy (RT). However, in veterinary nursing, objective evaluation of the condition of dogs after RT using thermography has not been reported. We investigated the nasal irradiation temperature, behavioral changes, and post-irradiation pain scores in a dog receiving RT for intranasal tumors. The temperature of the nasal planum gradually increased after irradiation, reaching a significantly higher value at 120-240 min. The highest temperature was 42.3 °C and the average temperature increased by 4.4 °C. Behavioral analysis pre- and post-RT did not vary significantly. Post-RT pain levels evaluated by the pain scale ranged from 0 to 1 throughout. No veterinary treatment was provided. In humans, increased skin temperature after radiation causes psychological stress, i.e., pain and discomfort, but no such behavioral changes were observed in this case. Given individual differences in stress-related behaviors, such as pain and discomfort, assessing a dog's painfulness using only subjective methods, such as appearance and behavioral evaluation, is limited. We used thermography to assess changes in conditions not detectable by routine monitoring alone. This method is non-invasive, objective, and indispensable for providing appropriate care.

Establishment of a canine lens epithelial cell line.

Some immortalized lens epithelial cell lines have been established and are useful for molecular analysis. The establishment of additional cell lines must, however, enable a variety of in-vitro examinations. The objective of this study was to establish a new canine lens epithelial cell line by isolating CLC-1 cells from the lens tissue of a dog with cataracts. In CLC-1 cells, transforming growth factor beta (TGF-ß) treatment significantly decreased gene expression of an epithelial marker and elevated that of mesenchymal markers; these characteristics are similar to those of a human lens epithelial cell line. Interestingly, CLC-1 cells exhibited lower expression of an epithelial marker and higher expression of mesenchymal markers than an anterior lens capsule. These results suggest that CLC-1 cells were derived from a cell population that was committed to epithelial-mesenchymal transition in cataract lens tissue. In conclusion, CLC-1 cells could be useful for analyzing molecular pathogenesis in canine cataracts.

Certaines lignées de cellules épithéliales du cristallin immortalisées ont été établies et sont utiles pour analyse moléculaire. L'établissement de lignées cellulaires supplémentaires doit cependant permettre une variété d'examens in vitro. L'objectif de cette étude était d'établir une nouvelle lignée cellulaire épithéliale du cristallin canin en isolant les cellules CLC-1 du tissu du cristallin d'un chien atteint de cataracte. Dans les cellules CLC-1, le traitement par le facteur de croissance transformant bêta (TGF-ß) a significativement diminué l'expression génique d'un marqueur épithélial et élevé celle des marqueurs mésenchymateux; ces caractéristiques sont similaires à celles d'une lignée cellulaire épithéliale du cristallin humain. Fait intéressant, les cellules CLC-1 présentaient une expression inférieure d'un marqueur épithélial et une expression plus élevée de marqueurs mésenchymateux qu'une capsule antérieure du cristallin. Ces résultats suggèrent que les cellules CLC-1 étaient dérivées d'une population cellulaire qui était impliquée dans la transition épithéliale-mésenchymateuse dans le tissu du cristallin de la cataracte. En conclusion, les cellules CLC-1 pourraient être utiles pour analyser la pathogenèse moléculaire dans les cataractes canines.(Traduit par Docteur Serge Messier).

Dysuria Associated with Non-Neoplastic Bone Hyperplasia of the Os Penis in a Pug Dog.

A three-year-old male Pug presented with a three-year history of urolithiasis and repeated urethral obstruction. Biochemical analysis, ultrasonography, and retrograde urethrocystography revealed probable portosystemic shunt and incomplete urethral obstruction due to uric acid ammonium calculi. Enhanced computed tomography (CT) revealed portosystemic shunt and proliferation of the osseous tissue of the os penis, which was surgically removed. Histopathologically, the excised osseous tissue comprised bland lamellar bone without atypia or inflammation. Hyperplasia of the os penis was diagnosed based on the image findings and histopathology. The dysuria improved postoperatively. This is the first report of dysuria associated with non-neoplastic bone hyperplasia of the os penis in a dog. Careful evaluation of the os penis by CT is needed for accurate diagnosis in case of repeated penile urethral obstruction.

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy.

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.

Analyses of a satiety factor NUCB2/nesfatin-1; gene expressions and modulation by different dietary components in dogs.

Nesfatin-1 is an anorexic peptide derived from a precursor, nucleobindin-2 (NUCB2), which is distributed in various organs, coexists with ghrelin in the gastric X/A-like cells and closely relates to an appetite control in rodents and humans. Nesfatin-1 may be a significant factor addressing the satiety also in veterinary medicine, however, there are few reports about nesfatin-1 in dogs. In the present study, we detected canine NUCB2/nesfatin-1 mRNA in various tissues, especially abundant in pancreas, gastrointestinal tracts, testis and cerebellum. We examined circulating nesfatin-1 concentrations and NUCB2/nesfatin-1 mRNA expressions in upper gastrointestinal tracts (gastric corpus, pyloric antrum and duodenum) in dogs fed on different types of diets. Plasma nesfatin-1 concentrations in the dogs were approximately 4 ng/ml and they did not change after feeding through the study, however, NUCB2/nesfatin-1 mRNA expressions in pyloric antrum were 1.84-fold higher in the dogs fed on a High fiber/High protein diet (P<0.001), 1.48-fold higher in the dogs fed on a High fat/Low protein diet (P<0.05) and 1.02-fold higher in the dogs fed on a Low fat/High carbohydrate diet (not significant) comparing to those on a control diet. It was concluded that High fiber/High protein and High fat/Low protein diets increased NUCB2/nesfatin-1 production in canine gastrointestinal tracts. These results may set the stage for further investigations of canine NUCB2/nesfatin-1, which may relate to satiety effects in dogs.

Preliminary study characterizing the use of sitagliptin for glycemic control in healthy Beagle dogs with normal gluco-homeostasis.

Sitagliptin is a dipeptidyl peptidase-4 inhibitor aimed at treating Type 2 diabetes mellitus (T2DM) and T1DM, by increasing blood levels of Glucagon-like peptide 1 (GLP-1) and insulin. The objective of this preliminary study is to characterize Sitagliptin's ability for glycemic control, in healthy dogs under an oral glucose tolerance test (OGTT) environment. Overall, Sitagliptin did not result in any significant changes to temporal glucose and insulin concentrations. However, a ~55% increase in median total GLP-1 AUC0-120 min was observed, as compared to baseline control in healthy dogs (n=5), thus indicating a similar mode of action of Sitagliptin between healthy dogs and humans. Future studies to validate the use of Sitagliptin with dogs suffering from insulin independent diabetes are warranted.

Decreased gene expressions of insulin signal molecules in canine hyperadrenocorticism.

Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, in which excess glucocorticoid causes insulin resistance. Disturbance of insulin action may be caused by multiple factors, including transcriptional modulation of insulin signal molecules which lie downstream of insulin binding to insulin receptors. In this study, gene expressions of insulin signal molecules were examined using neutrophils of the HAC dogs (the untreated dogs and the dogs which had been treated with trilostane). Insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B/Akt kinase (Akt)-2 and protein kinase C (PKC)-lambda were analyzed in the HAC dogs and compared with those from normal dogs. The IRS-1 gene expressions decreased by 37% and 35% of the control dogs in the untreated and treated groups, respectively. The IRS-2 gene expressions decreased by 61% and 72%, the PI3-K gene expressions decreased by 47% and 55%, and the Akt-2 gene expressions decreased by 45% and 56% of the control dogs, similarly. Collectively, gene expressions of insulin signal molecules are suppressed in the HAC dogs, which may partially contribute to the induction of insulin resistance.

Impact of commercially available diabetic prescription diets on short-term postprandial serum glucose, insulin, triglyceride and free fatty acid concentrations of obese cats.

Diet therapy is an important treatment component available for obese cats. In this study, the impact of four commercially available prescription diet regimens (1 for general use and 3 aimed at treating obesity and diabetes mellitus (DM)) on short-term postprandial serum glucose, insulin, triglyceride and nonesterified fatty acid (NEFA) concentrations was investigated with five obese cats. The diet regimens used were as follows: C/D dry (general use: moderate protein, moderate fat, high carbohydrate and low fiber), M/D dry (DM: high protein, high fat, low carbohydrate and high fiber), W/D dry (DM: high protein, low fat, high carbohydrate and high fiber) and Diabetic dry (DM: high protein, low fat, low carbohydrate and high fiber). A significant reduction (10-13%) in postprandial glucose (area under the curve; AUC) was observed with the M/D and Diabetic diets, which both contained lower concentrations of carbohydrates than the C/D diet. An accompanying significant reduction (30-36%) in postprandial insulin AUC was also observed with the three DM diets, which all had higher amounts of fiber, as compared with the C/D diet. Lastly, a significant increase (32-65%) in postprandial NEFA AUC was observed with the M/D and Diabetic diets as compared with the C/D diet. Therefore, dietary amounts of carbohydrates and fiber, as opposed to protein content or dietary fat, appear to have a very significant impact on postprandial glycemia and subsequent insulin requirement levels in obese cats. In addition, dietary amounts of carbohydrates may also impact lipid metabolism in obese cats.

Comparison of glucose fluctuations between day- and night-time measured using a continuous glucose monitoring system in diabetic dogs.

Monitoring of blood glucose concentration is important to evaluate the diabetic status of dogs. Continuous glucose monitoring systems (CGMS) have been applied in veterinary medicine for glucose monitoring in diabetic dogs. The purpose of the study was to evaluate the daily glycemic profiles obtained with CGMS and compare glucose fluctuations between day- and night-time in diabetic dogs. Five diabetic dogs were used in this study and were treated with either NPH insulin or insulin detemir. For data analyses, day-time was defined as 9:00 am-9:00 pm and night-time as 9:00 pm-9:00 am. Using glucose profiles, we determined the mean glucose concentrations (1- and 12-hr intervals), and times spent in hyperglycemia >200 mg/dl or hypoglycemia <60 mg/dl. None of the parameters differed significantly between day-time and night-time in dogs treated with NPH insulin or insulin detemir. In conclusion, this study confirmed, using CGMS, that there are no differences in glucose fluctuations between day- and night-time, in diabetic dogs on a similar feeding regimen and insulin administration.

Characterization and comparison of insulin resistance induced by Cushing Syndrome or diestrus against healthy control dogs as determined by euglycemic- hyperinsulinemic glucose clamp profile glucose infusion rate using an artificial pancreas apparatus.

Euglycemic-hyperinsulinemic glucose clamp (EHGC) method is a gold standard for assessing insulin resistance in humans. However, this method has yet to be commonly used with dogs, due to the requirement of frequent blood sampling for glucose measurement and adjusting glucose infusion rate (GIR). The purpose of this study was to evaluate insulin resistance, induced either by Cushing Syndrome (CS) or diestrus in dogs, as determined by GIR by EHGC, using an artificial pancreas apparatus. Twenty animals were used in this study with ten (7 females and 3 males) serving as healthy controls, four (3 females, 1 male) diagnosed with CS, and six (all females) undergoing diestrus. A higher GIR value indicates increased insulin sensitivity and lower insulin resistance. GIR of healthy control animals was determined to be within a reference range of [10.6-21.3] with a median of 15.2 mg/kg/min. In comparison, the CS group had a median of 5.4 mg/kg/min; whereas the diestrus group exhibited a median of 8.9 mg/kg/min. Insulin resistant animals suffering from CS and undergoing diestrus demonstrated reductions of 65 and 40% in GIR, respectively; thus indicating differences in degree of insulin insensitivity can be discerned using the EHGC method.

Evaluation of serum and urine 1,5-anhydro-D-glucitol and myo-inositol concentrations in healthy dogs.

1,5-anhydro-D-glucitol (1,5AG) is a pyranoid polyol compound found in human circulating blood. Myo-inositol (MI) is a stereoisomer of inositol and serves as a precursor of inositol phospholipids. 1,5AG and MI are filtered by the glomerulus and almost completely reabsorbed through the renal tubules. However, under hyperglycemic conditions, reabsorption through the renal tubules is competitively inhibited because the structures of 1,5AG and MI resemble that of glucose. In this study, we investigated the kinetics of serum and urine 1,5AG and MI levels in healthy dogs. We demonstrated that 1,5AG and MI exist in canine serum and urine by gas chromatography-mass spectrometry. Under continuous hyperglycemic conditions, the serum 1,5AG concentration in healthy dogs decreased while the serum MI concentration remained unchanged. Urinary excretion of 1,5AG and MI increased significantly after blood glucose concentrations reached 200 to 220 mg/dl. A significant negative correlation was observed between serum 1,5AG and glucose concentrations during hyperglycemia. However, no significant correlation was observed between serum MI and glucose concentrations. In this study, we demonstrated that serum and urine 1,5AG and MI levels were changed by blood glucose concentrations. The serum 1,5AG concentration was decreased by continuous hyperglycemia. However, the serum MI concentration does not reflect hyperglycemia.

Evaluation of artificial pancreas technology for continuous blood glucose monitoring in dogs.

Artificial pancreas technology, involving "closed-loop" controls with real-time blood glucose monitoring, has been increasing in reliability as its potential for clinical use and application grows. One such device, based on this technology, is the STG-22 (Nikkiso Co., Ltd., Tokyo, Japan) artificial pancreas apparatus. In order to assess the reliability and accuracy of the device for measuring blood glucose, it is important to compare its readings to those obtained using a 'gold standard' method, such as the hexokinase method. Therefore, in the present study, canine blood [glucose] measurements using the STG-22 were compared to those obtained using a previously established commercial reagent, Quickauto-Neo GLU-HK. Furthermore, two different sample types (whole blood versus plasma constituent) were compared to determine which sample type results in more accurate and optimal readings with the STG-22. Given that the STG-22 was not primarily designed for canine blood samples, results for canine blood samples were not accurate. Measurements performed by the STG-22 with whole blood were significantly lower than reference [glucose] counterparts. Alternatively, an opposite trend was observed with plasma measurements that were significantly higher. A conversion format using the following formula, Hexokinase [glucose] = STG-22 [glucose] × 1.407 + 1.532, was observed with canine samples in our study.

Age-specific plasma biochemistry reference ranges in <1 year old dogs in Japan.

The purpose of this study was to investigate and propose possible reference intervals of plasma biochemical analytes in young dogs (<12 months old) in Japan, using 896 canine plasma samples, collected from an array of veterinary clinics throughout the greater Tokyo metropolis area in Japan. The following biochemical parameters were assessed: albumin (ALB), alanine aminotransferase (ALT), alkaline phosphatase (ALP), amylase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (CRE), glucose, lipase, total cholesterol (T-Cho), and total protein (TP) were evaluated. Multivariate linear regression analysis indicated that partitioning according to age or gender may be necessary for some plasma analytes. Age appeared to significantly affect ALB, ALT, ALP, BUN, Glucose, Lipase, and Total Protein (P= <0.001, <0.001, <0.001, 0.013, <0.001, 0.025, and <0.001, respectively). On the other hand, gender significantly influenced ALP, Amylase, Lipase, and T-Cho levels (P=0.017, <0.001, <0.001, and <0.001, respectively) whereas it may be borderline significant with ALT (P=0.072).

Supplementing transglucosidase with a high-fiber diet for prevention of postprandial hyperglycemia in streptozotocin-induced diabetic dogs.

Indigestible oligosaccharides have been shown to normalize blood glucose and insulin concentration thereby promoting good health and preventing diseases, such as diabetes. Transglucosidase (TG, alpha-glucosidase, enzyme code (EC) 3.2.1.20) is an enzyme capable of converting starch to oligosaccharides, such as iso-malto-oligosaccharides from maltose, via the action of amylase. The aim of this study was to evaluate whether oral administration of TG with maltose or dextrin is capable of reducing post-prandial serum glucose concentration in experimentally streptozotocin (STZ)-induced diabetic dogs fed on a high-fiber diet. Five healthy and five STZ-induced diabetic dogs were employed in this study. TG supplementation with dextrin or maltose had no detrimental effect in healthy dogs. In fact, TG and dextrin exhibited a flatlined serum glucose pattern, while reducing mean post-prandial serum insulin and glucose concentration as compared to control diet alone. When TG supplementation was tested in STZ-induced diabetic dogs under the context of a high fiber diet, a 13.8% and 23.9% reduction in mean glucose concentration for TG with maltose and dextrin, respectively was observed. Moreover, TG with dextrin resulted in a 13% lower mean post-prandial glucose concentration than TG with maltose, suggesting that dextrin may be a more efficient substrate than maltose when used at the same concentration (1 g/kg). Our results indicate that TG supplementation with diet can lead to lower postprandial glucose levels versus diet alone. However, the efficacy of TG supplementation may depend on the type of diet it is supplemented with. As such, TG administration may be useful for preventing the progression of diabetes mellitus and in its management in dogs.

A selective small molecule glucagon-like peptide-1 secretagogue acting via depolarization-coupled Ca(2+) influx.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates insulin secretion in a glucose-dependent manner. Selective GLP-1 secretagogue would be one of the potential therapeutic targets for type 2 diabetes. Here, we describe a newly identified small molecule compound (compound A) that stimulates secretion of GLP-1 in murine enteroendocrine cell lines, STC-1 and GLUTag cells, and in primary cultured fetal rat intestinal cells (FRIC). The underlying mechanism by which compound A stimulated GLP-1 secretion was also examined. Compound A stimulated GLP-1 secretion from STC-1 cells in a concentration-dependent manner, and also from GLUTag cells and FRIC. The action of compound A was selective against other tested endocrine functions such as secretion of insulin from rat islets, growth hormone from rat pituitary gland cells, and norepinephrine from rat PC-12 cells. In STC-1 cells, the compound A-stimulated GLP-1 secretion was neither due to cyclic AMP production nor to Ca(2+) release from intracellular stores, but to extracellular Ca(2+) influx. The response was inhibited by the presence of either L-type Ca(2+) channel blockers or K(+) ionophore. Perforated-patch clamp study revealed that compound A induces membrane depolarization. These results suggest that neither Galphas- nor Galphaq-coupled signaling account for the mechanism of action, but depolarization-coupled Ca(2+) influx from extracellular space is the primary cause for the GLP-1 secretion stimulated by compound A. Identifying a specific target molecule for compound A will reveal a selective regulatory pathway that leads to depolarization-mediated GLP-1 secretion.