Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and is depressed in Clock mutants, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycaemia is retained. Furthermore, a high-fat diet modulates carbohydrate metabolism by amplifying circadian variation in glucose tolerance and insulin sensitivity, and mutation of Clock restores the chow-fed phenotype. Bmal1 and Clock, genes that function in the core molecular clock, exert profound control over recovery from insulin-induced hypoglycaemia. Furthermore, asynchronous dietary cues may modify glucose homeostasis via their interactions with peripheral molecular clocks.

Background— Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results— With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions— Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Insulin resistance is considered a risk factor in obesity, laminitis, exertional rhabdomyolysis, and osteochondrosis. The objective was to use the minimal model to estimate glucose effectiveness (Sg) and insulin sensitivity (Si) in nonobese to obese horses initially adapted to forage only, then adapted to forage plus supplements rich in starch and sugar (SS) or fiber and fat (FF). Ten Thoroughbred geldings, with BCS of 5 (nonobese), 6 (moderately obese), and 7 to 8 (obese), were adapted to pasture and hay, allocated to two groups, and fed SS or FF in a switch-back design with 8 wk of adaptation. Modified frequent-sampling i.v. glucose tolerance tests were applied after adaptation to forage, SS, and FF. For the tolerance tests, horses were kept in stalls overnight and provided hay, and venous catheters were placed the next morning. Baseline samples were collected, 0.3 g of glucose/kg of BW was given i.v., and blood was sampled at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 19 min. At 20 min, 30 mU of insulin/kg of BW was given, followed by sampling at 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 min. Plasma was analyzed for glucose and insulin, and Si, Sg, acute insulin response to glucose, and the disposition index were calculated. Normality was tested using the Shapiro-Wilk statistic. Body condition effects were analyzed using a mixed model with repeated measures. Diet effects were analyzed using a Wilcoxon signed rank test. The Sg was higher in obese than nonobese (P = 0.003) and moderately obese (P = 0.007) horses; Si was lower in obese than nonobese (P = 0.008) horses, and acute insulin response to glucose was higher in obese than nonobese (P = 0.039) horses. Effects of diet were likely confounded by body condition, but horses had lower Si (P = 0.066) when fed SS compared with FF, especially when nonobese. In conclusion, the minimal model effectively estimated Sg, Si, acute insulin response to glucose, and disposition index in horses. Obese geldings were insulin-resistant and seemed to rely primarily on Sg for glucose disposal. Feeding a diet rich in sugar and starch decreased insulin sensitivity of horses. Maintenance of body condition and avoidance of grain-based meals rich in sugar and starch would be beneficial to decrease the risk of developing insulin resistance and associated metabolic syndromes in horses, especially for horses at risk for these syndromes.

Objective-To determine whether the Canine Brief Pain Inventory (CBPI) can detect changes in dogs with osteoarthritis treated with an NSAID or a placebo.Design-Double-blind, randomized, placebo-controlled clinical trial. Animals-70 dogs with osteoarthritis.Procedures-Owners completed the CBPI on day 0. Dogs received carprofen or a placebo on days 1 through 14. Owners completed the CBPI again on day 14. Pain severity and pain interference scores from the CBPI were calculated, and the change from day 0 to day 14 was assessed within each group and between groups.Results-No significant differences were detected in median scores for pain severity (3.50 and 3.25 on days 0 and 14, respectively) and pain interference (3.92 and 3.25 on days 0 and 14, respectively) in dogs receiving the placebo. Dogs receiving carprofen had significant changes in median scores for pain severity (4.25 to 2.25 on days 0 and 14, respectively) and pain interference (4.33 to 2.67 on days 0 and 14, respectively). There was a significantly greater improvement in pain severity and pain interference scores in dogs treated with carprofen, compared with improvement in scores for dogs receiving the placebo.Conclusions and Clinical Relevance-The CBPI was able to detect improvements in pain scores in dogs with osteoarthritis treated with an NSAID or a placebo. These results, in combination with previous reliability and validity testing, support the use of the CBPI to obtain quantifiable assessments from owners regarding the severity and impact of chronic pain and treatment for dogs with osteoarthritis.The availability of quantitative measures of chronic pain that are valid and reliable in clinical patients is crucial for the development and testing of interventions (eg, drugs or surgical procedures) designed to reduce such pain. Studies designed to test the efficacy of interventions intended to decrease chronic pain in companion dogs with osteoarthritis have relied heavily on a veterinarian's assessment of lameness supported by values generated through the use of force plate gait analysis. When properly collected, gait analysis data offer an objective measure that can be reliably monitored over time; however, it can be an extremely time-consuming process, requires specialized equipment, and relies on relatively strict inclusion criteria. In addition, these measures only evaluate an animal at 1 specific time point and outside of its typical environment, and weight bearing on an affected limb is only 1 part of the much larger picture of chronic pain in companion dogs with osteoarthritis. 1-5 A detailed behavior-based

A X bstract. The highly polyunsaturated fatty acids in fish oils lower the plasma triglyceride concentration. We have studied the effect of a diet rich in fish oil on the rate of production of the triglyceride-transporting very low density lipoprotein (VLDL). Seven subjects, five normal and two with hypertriglyceridemia received up to 30% of daily energy needs from a fish oil preparation that was rich in eicosapentaenoic acid and docosahexaenoic acid, w-3 fatty acids with five and six double bonds, respectively.Compared with a diet similarly enriched with safflower oil (in which the predominant fatty acid is the w-6 linoleic acid, with two double bonds), the fish oil diet lowered VLDL lipids and B apoprotein concentrations profoundly.High density lipoprotein lipids and Al apoprotein were also lowered, but the effect on low density lipoprotein (LDL) concentration was inconsistent.The daily production or flux of VLDL apoprotein B, calculated from reinjected autologous '25I-labeled lipoprotein, was substantially less in six subjects studied after 3 wk of fish oil, compared with after safflower oil. This effect on flux was more consistent than that on the irreversible fractional removal rate, which was increased in the four normolipidemic but inconsistent in the hyThis work was presented in part at

Objective-To develop and psychometrically test an owner self-administered questionnaire designed to assess severity and impact of chronic pain in dogs with osteoarthritis.Sample Population-70 owners of dogs with osteoarthritis and 50 owners of clinically normal dogs.Procedures-Standard methods for the stepwise development and testing of instruments designed to assess subjective states were used. Items were generated through focus groups and an expert panel. Items were tested for readability and ambiguity, and poorly performing items were removed. The reduced set of items was subjected to factor analysis, reliability testing, and validity testing.Results-Severity of pain and interference with function were 2 factors identified and named on the basis of the items contained in them. Cronbach's α was 0.93 and 0.89, respectively, suggesting that the items in each factor could be assessed as a group to compute factor scores (ie, severity score and interference score). The test-retest analysis revealed κ values of 0.75 for the severity score and 0.81 for the interference score. Scores correlated moderately well (r = 0.51 and 0.50, respectively) with the overall quality-of-life (QOL) question, such that as severity and interference scores increased, QOL decreased. Clinically normal dogs had significantly lower severity and interference scores than dogs with osteoarthritis. Conclusions and Clinical Relevance-A psychometrically sound instrument was developed.Responsiveness testing must be conducted to determine whether the questionnaire will be useful in reliably obtaining quantifiable assessments from owners regarding the severity and impact of chronic pain and its treatment on dogs with osteoarthritis.It is crucial to have quantitative measures of chronic pain that are valid and reliable in clinical patients to enable development and testing of interventions (such as drugs or surgical procedures) designed to reduce such pain. In the past, studies designed to test the efficacy of interventions intended to decrease chronic pain in dogs with osteoarthritis have relied heavily on a veterinarian's assessment of lameness supported by values generated through gait analysis by use of a force plate. When collected properly, data on gait analysis offer an objective measure that can be reliably monitored over time; however, it can be extremely time consuming, requires specialized equipment, and relies on relatively strict inclusion criteria. In addition, these measures only evaluate an animal at 1 specific point in NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript time, and weight bearing on an affected limb is only 1 part of the much larger picture of chronic pain in dogs with osteoarthritis. [1][2][3][4][5] When an owner brings a dog to a veterinarian with a concern that the dog has signs of a chronic painful condition, they report a number of behaviors that they attribute to the painful condition (eg, no longer climbs stairs or jumps onto the bed). In monitoring the progression of the dog's cond...

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus −0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

In African Americans, TG levels and TG-HDL-C ratio are not reliable markers of insulin resistance.