Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest.

Aberrant levels of preadipocyte differentiation, triggered by adipocyte hyperplasia and hypertrophy, results in the obesogenic phenotype. Obesity is a risk factor for several metabolic disorders. In this paper, dehydroleucodine inhibited the accumulation of lipid droplets and decreased the elevations of triglycerides, and this inhibitory effect occurred during the early stage of adipogenesis. Thus, not only did dehydroleucodine downregulate the expression of C/EBPα and PPARγ, it also strongly blocked the expression of C/EBPß, an early stage biomarker of early adipogenesis, in a concentration-dependent manner. The proliferation of preadipocytes was dramatically suppressed when dehydroleucodine was added to the medium as early as 24 hr. These results indicate that dehydroleucodine may specifically affect mitotic clonal expansion to inhibit preadipocyte differentiation. Dehydroleucodine arrested the cell cycle at the G0 /G1 phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). Additionally, dehydroleucodine decreased phosphorylation of Erk1/2 and Akt. Furthermore, dehydroleucodine downregulated expression of histone demethylase JMJD2B as well as repressed the expression of histone methyltransferase MLL4, which in turn diminished the expression of C/EBPß and PPARγ, respectively. Collectively, our results indicate that dehydroleucodine inhibits preadipocyte differentiation by blocking mitotic clonal expansion via cell cycle arrest, which may be mediated by regulation of selective histone methylation/demethylation in transcription activation during the early step of adipogenesis.

Fish oil supplementation increases concentration of adiponectin in healthy dogs.

OBJECTIVE: To determine the effect of fish oil supplementation on circulating concentrations of adiponectin, leptin, insulin, glucose, triglyceride and cholesterol in healthy dogs. METHODS: Twenty healthy adult dogs were administered 220 mg/kg of a fish oil supplement once daily for 30 days. At baseline, on supplement and 10 to 20 weeks off supplement, dogs were examined, body condition scores determined (range: 4 to 6), body measurements recorded for % body fat calculation and fasted blood samples collected. RESULTS: Serum concentrations of the measured individual and total n-3 polyunsaturated fatty acids increased following supplementation (P<0·001). Mean serum adiponectin concentration on supplement was 3·4 µg/mL (95% confidence interval: 0·8 to 6·0; P=0·006) higher than baseline, and 5·3 µg/mL (2·0 to 8·7; P<0·001) higher than off supplement. Concentrations of adiponectin off supplement were not different from baseline. There were no significant differences in weight, body condition scores, % body fat and concentrations of other measured analytes between baseline and on supplement. CLINICAL SIGNIFICANCE: Fish oil supplementation significantly increased circulating concentration of adiponectin in healthy non-obese dogs. Further investigation is warranted to determine whether this effect may be extended to obese dogs and to evaluate the potential role of fish oil supplementation in the management of disorders associated with low circulating adiponectin concentrations.

Alterations in adipokines in feline hepatic lipidosis.

BACKGROUND: Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. HYPOTHESIS: Serum concentrations of adiponectin and leptin are altered in feline HL. ANIMALS: Client-owned cats: 55 healthy and 45 with liver disease. METHODS: Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. RESULTS: Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 µg/mL), HL and concurrent disease (4.4 µg/mL), or other liver disease (6.1 µg/mL), as compared with healthy cats (1.5 µg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. CONCLUSIONS AND CLINICAL IMPORTANCE: Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL.

Cardiac effect of short-term experimental weight gain and loss in dogs.

During 12 weeks, 18 normal dogs were fed a high-caloric diet intended to induce obesity (weight-gain phase). For the next 12 weeks (weight-loss phase), all dogs were fed a diet calculated to provide maintenance needs. During this second phase, dogs were randomly assigned to three groups differing only in their exercise regimen: group 1 dogs were not exercised, group 2 dogs were exercised three times each week on a treadmill, group 3 dogs were similarly exercised and outfitted with a vest holding additional weights. Echocardiographic data were obtained at baseline and following both the weight-gain and weight-loss phases. The weight-gain phase of the study was associated with an increase in bodyweight (31.4 per cent), decrease in body density (3.9 per cent) and an increase in left ventricular (LV) myocardial cross-sectional area in all groups. Cardiac hypertrophy was variably reversible during the weight-loss phase, with complete recovery for group 1, partial recovery for group 2 and no recovery in group 3. Regardless of group, weight loss was associated with a significant increase in LV diameter, a reduction of heart rate and an increase in heart rate-corrected isovolumetric relaxation time.

Intermittent and continuous enteral nutrition in critically ill dogs: a prospective randomized trial.

BACKGROUND: Malnutrition is a common problem in critically ill dogs and is associated with increased morbidity and mortality in human medicine. Enteral nutrition (EN) delivery methods have been evaluated in humans to determine which is most effective in achieving caloric goals. OBJECTIVES: To compare continuous infusion and intermittent bolus feeding of EN in dogs admitted to a critical care unit. ANIMALS: Fifty-four dogs admitted to the critical care unit and requiring nutritional support with a nasoenteric feeding tube. METHODS: Prospective randomized clinical trial. Dogs were randomized to receive either continuous infusion (Group C) or intermittent bolus feeding (Group I) of liquid EN. The percentage of prescribed nutrition delivered (PPND) was calculated every 24 hours. Frequencies of gastrointestinal (GI), mechanical, and technical complications were recorded and gastric residual volumes (GRVs) were measured. RESULTS: PPND was significantly lower in Group C (98.4%) than Group I (100%). There was no significant difference in GI or mechanical complications, although Group C had a significantly higher rate of technical complications. GRVs did not differ significantly between Group C (3.1 mL/kg) and Group I (6.3 mL/kg) and were not correlated with the incidence of vomiting or regurgitation. CONCLUSIONS AND CLINICAL IMPORTANCE: There was a statistically significant difference in the PPND between continuously and intermittently fed dogs, but this difference is unlikely to be clinically relevant. Critically ill dogs can be successfully supported with either continuous infusion or intermittent bolus feeding of EN with few complications. Increased GRVs may not warrant termination of enteral feeding.

Specificity of task constraints and effects of visual demonstrations and verbal instructions in directing learners' search during skill acquisition.

In the present study, the efficacy of visual demonstrations and verbal instructions as instructional constraints on the acquisition of movement coordination was investigated. Fifteen participants performed an aiming task on 100 acquisition and 20 retention trials, under 1 of 3 conditions: a modeling group (MG), a verbally directed group (VDG), and a control group (CG). The MG observed a model intermittently throughout acquisition, whereas the VDG was verbally instructed to use the model's movement pattern. Participants in the CG received neither form of instruction. Kinematic analysis revealed that compared with verbal instructions or no instructions, visual demonstrations significantly improved participants' approximation of the model's coordination pattern. No differences were found in movement outcomes. Coordination data supported the visual perception perspective on observational learning, whereas outcome data suggested that the modeling effect is mainly a function of task constraints, that is, the novelty of a movement pattern.

Effects of manipulating relative and absolute motion information during observational learning of an aiming task.

In the visual perception perspective of observational learning, the manipulation of relative and absolute motion information in visual demonstrations optimally directs learners' search towards appropriate task solutions. We assessed the effect of emphasizing transformational information and removal of structural information using point-light kinematic displays in approximating the model's relative motion patterns. Participants viewed computer-simulated point-light demonstrations or normal video demonstrations before and intermittently throughout 100 acquisition trials with knowledge of results on an underarm modified-dart aiming task. On the next day, all participants performed 20 retention trials without demonstrations. The kinematics of spatial and temporal coordination and control variables were examined relative to the model's action, as well as performance scores. The results indicated that approximation of the model's spatial and temporal coordination and control patterns was achieved after observation of either type of demonstrations. No differences were found in movement outcomes. In a second experiment, the effects of manipulating absolute motion information by slow-motion demonstrations were examined relative to real-time demonstrations. Real-time demonstrations led to a closer approximation to the model's spatial and temporal coordination patterns and better outcome scores, contradicting predictions that slow-motion displays convey intact relative motion information. We speculate that the effect of visual demonstration speed on action perception and reproduction is a function of task constraints--that is, novelty or familiarity of relative motion of demonstrated activities.

Determination of age in dogs and cats by use of changes in lens reflections and transparency.

OBJECTIVE: To develop and test a noninvasive technique for determining age in dogs and cats on the basis of changes in lens reflections and transparency. ANIMALS: 85 dogs representing 5 breeds and 73 domestic shorthair cats. PROCEDURE: While examining dilated eyes in a darkened room, using a penlight, 2 experienced examiners who were blinded to actual age of animals individually measured the diameter of reflections from the anterior (La) and posterior (Lb) surfaces of the lens and scored lens transparency (Ltr) from 1 (clear) to 5 (severe opacity). Models were developed to predict age on the basis of these measurements. RESULTS: Aging models developed for dogs and cats were as follows: Age(dogs) = 2.197 - 0.070 x (La) + 1.361 x (Lb) + 1.193 x (Ltr) and Age(cats) = 1.988 + 1.024 x (La) + 2.220 x (Lb) + 1.019 x (Ltr), where age was expressed in years, and La and Lb were in millimeters. All variables, except La in dogs, contributed significantly to accuracy of the models. Correlation between predicted and actual ages, as measured by Pearson's product-moment correlation coefficient, was significant in both species (P < 0.0001). Significant differences were not found between examiners or between the first and second evaluations by the same examiner. CONCLUSIONS AND CLINICAL RELEVANCE: A noninvasive technique based on evaluation of lens reflections and transparency can provide clinically useful predictions of age in mature dogs and cats. This technique could be an important tool for veterinarians or humane shelters in determining differential diagnoses and assessing longevity and adoptability of mature animals of unknown age.

Hyperlipemia in 9 miniature horses and miniature donkeys.

The medical records from 9 consecutive miniature horses (n = 5) and miniature donkeys (n = 4) with hyperlipemia (serum triglyceride concentration > 500 mg/dL) were reviewed. In all cases, hyperlipemia was a secondary complication of a primary systemic disease including septicemia, colitis, parasitism, esophageal obstruction, gastric impaction and rupture, fecalith, and pituitary adenoma. Therapy consisted of specific treatment for the primary disease, supportive care, and nutritional support. The mean time for resolution of hyperlipemia in cases requiring nutritional support (n = 6) was 7 days, and the duration of nutritional support in surviving patients was 11.7 days. Seven of 9 patients survived. The primary disease resulted in death in 2 patients. Enteral feeding with commercially prepared low residue diets and treatment of the primary disease was successful in reversing hyperlipemia in 5 of 6 surviving patients that required nutritional support. Parenteral administration of a glucose-based (non-lipid) solution was successful in resolving hyperlipemia in 1 patient.

New technique and management guidelines for percutaneous nonendoscopic tube gastrostomy.

A percutaneous nonendoscopic gastrostomy tube placement device and a new technique for nonendoscopic gastric feeding tube placement were developed for use in animals weighing < 15 kg. After a successful experimental trial in 7 cats, the tube placement device was used in 8 clinical animals (7 cats and 1 dog). All gastrostomy feeding tubes were placed on the first attempt within 10 minutes. Position of the tube was evaluated by endoscopy in 14 of 15, by radiography in 4 of 15, and by celiotomy and necropsy in 2 of 15 animals, respectively. Placement was comparable to the percutaneous endoscopic technique in all but 1 cat. In this animal, the tube had to be placed existing the skin in a caudoventral location because of severe panniculitis. Complications related to the use of the tube placement device were not observed. Complications related to gastrostomy tube management developed in 5 of 15 animals. The prevalence of clinically important or life-threatening complications (peritonitis or premature removal) was 3 of 15.

Enteral feeding of dogs and cats: 51 cases (1989-1991).

Feeding commercial enteral diets to critically ill dogs and cats via nasogastric tubes was an appropriate means for providing nutritional support and was associated with few complications. Twenty-six cats and 25 dogs in the intensive care unit of our teaching hospital were evaluated for malnutrition and identified as candidates for nutritional support via nasogastric tube. Four commercial liquid formula diets and one protein supplement designed for use in human beings were fed to the dogs and cats. Outcome variables used to assess efficacy and safety of nutritional support were return to voluntary food intake, maintenance of body weight to within 10% of admission weight, and complications associated with feeding liquid diets. Sixty-three percent of animals experienced no complications with enteral feedings; resumption of food intake began for most animals (52%) while they were still in the hospital. Weight was maintained in 61% of the animals (16 of 26 cats and 15 of 25 dogs). Complications that did occur included vomiting, diarrhea, and inadvertent tube removal. Most problems were resolved by changing the diet or adhering to the recommended feeding protocol. Nutritional support as a component of therapy in small animals often is initiated late in the course of the disease when animals have not recovered as quickly as expected. If begun before the animal becomes nutrient depleted, enteral feeding may better support the animal and avoid serious complications.

Improved nasogastric intubation technique for administration of nutritional support in dogs.

Established procedures for nasogastric intubation are difficult to perform in dogs because of anatomic variation of nasal passages and turbinate structures. Twenty-five clinically normal dogs were used to improve and refine the technique of nasogastric tube placement, and 13 clinical patients at our teaching hospital were evaluated for malnutrition and were considered candidates for nutritional support by nasogastric tube feeding. An improved method for the placement of nasogastric tubes in dogs was used. By pushing the external nares dorsally while advancing the tube in a caudoventral, medial direction, the tube passed through the ventral meatus and into the oropharynx and esophagus easily. The procedure does not require chemical restraint, and the complication of epistaxis was not observed in any dog. Materials required to perform this technique are inexpensive, and the method can be used for the administration of nutritional support, fluids, drugs, or contrast material.