Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system.

AIMS: The effects of insulins detemir (Det) and glargine (Glar) on endogenous glucose production (EGP) and net hepatic glucose output (NHGO) were compared. METHODS: Arteriovenous difference and tracer ([3-(3) H]glucose) techniques were employed during a two-step hyperinsulinemic euglycaemic clamp in conscious dogs (6 groups, n = 5-6/group). After equilibration and basal sampling (0-120 min), somatostatin was infused and basal glucagon was replaced intraportally. Det or Glar was infused via portal vein (Po), peripheral vein (IV), or bilateral carotid and vertebral arteries (H) at 0.1 and 0.3 mU/kg/min (low Insulin; Glar vs. Det, respectively, 120-420 min) and 4× the low insulin rate (high insulin; 420-540 min). RESULTS: NHGO and EGP were suppressed and glucose R(d) and infusion rate were stimulated similarly by Det and Glar at both Low and high insulin with each infusion route. Non-esterified fatty acid (NEFA) concentrations during low insulin were 202 ± 37 versus 323 ± 75 µM in DetPo and GlarPo (p < 0.05) and 125 ± 39 versus 263 ± 48 µM in DetIV and GlarIV, respectively (p < 0.05). In DetH versus GlarH, pAkt/Akt (1.7 ± 0.2 vs. 1.0 ± 0.2) and pSTAT3/STAT3 (1.4 ± 0.2 vs. 1.0 ± 0.1) were significantly increased in the liver but not in the hypothalamus. CONCLUSIONS: Det and Glar have similar net effects on acute regulation of hepatic glucose metabolism in vivo regardless of delivery route. Portal and IV detemir delivery reduces circulating NEFA to a greater extent than glargine, and head detemir infusion enhances molecular signalling in the liver. These findings indicate a need for further examination of Det's central and hepatic effects.

Prospective evaluation of clinically relevant type B hyperlactatemia in dogs with cancer.

BACKGROUND: Cancer is considered a cause of type B hyperlactatemia in dogs. However, studies evaluating cancer as a cause of clinically relevant type B hyperlactatemia (>2.5 mmol/L) are lacking. Cancer cells have a higher lactate production because of increased aerobic glycolysis, known as the "Warburg effect." The mechanisms through which aerobic glycolysis occurs are not well elucidated, but neoplasia may cause type B hyperlactatemia via this process. OBJECTIVES: To determine if malignant tumors of dogs are associated with clinically relevant type B hyperlactatemia (>2.5 mmol/L). ANIMALS: Thirty-seven client-owned dogs with malignant tumors: 22 with hematopoietic and 15 with solid tumors. METHODS: Histology was used to confirm the diagnosis (cytology was considered adequate for diagnosis of lymphoma). Confounding conditions associated with hyperlactatemia were excluded. Lactate measurements were immediately performed on free-flow jugular whole blood samples using the LactatePro analyzer. RESULTS: All dogs had lactate concentrations<2.5 mmol/L. Mean blood lactate concentration was 1.09 mmol/L. Mean blood lactate concentrations for solid and hematopoietic tumors were 0.95 and 1.19 mmol/L, respectively. Dogs with lymphoma (n=18) had a mean blood lactate concentration of 1.15 mmol/L. CONCLUSIONS: Malignant tumors were not considered a cause of clinically relevant type B hyperlactatemia. Therefore, cancer-related type B hyperlactatemia in dogs is uncommon, and hyperlactatemia should prompt careful investigation for causes other than cancer.

Symbolic communication between two chimpanzees (Pan troglodytes).

Through use of learned symbols, two chimpanzees accurately specified 11 foods by name to one another when the food item's identity was known by only one. They could not do this when denied use of the symbols. The chimpanzees then spontaneously requested specific foods of one another by name. Requests resulted in cooperative and reciprocal symbolically mediated food exchange.

Effects of prednisone on blood lactate concentrations in healthy dogs.

BACKGROUND: Glucocorticoids affect carbohydrate and lactate metabolism. HYPOTHESIS: Administration of prednisone to healthy dogs will result in clinically relevant hyperlactatemia. ANIMALS: Twelve healthy adult Beagle dogs. METHODS: Prospective, controlled experimental study. Twelve healthy adult Beagles were divided into 2 groups (3 of each sex per group). One group served as control. The other group received 2 treatments: low, 1 mg/kg prednisone PO q24h for 2 weeks; high, 4 mg/kg prednisone PO q24h for 2 weeks. A washout period of 6 weeks separated the treatments. Blood samples were drawn for whole blood lactate measurement on day (D) 0, D4, and D14 and measured in duplicate. RESULTS: Compared with the control group, low and high groups had significantly higher blood lactate concentrations at D4 and D14. There was no difference at D0. There was no effect of time within the control group. In the low and high groups, blood lactate concentration was increased at D4 and D14 versus D0. Blood lactate concentration was greater in the high group than the low group at D14 only. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs treated with prednisone experience statistically significant increases in blood lactate concentrations, which can result in type B hyperlactatemia. In such cases, improving tissue perfusion, treatment for the commonest form of hyperlactatemia (type A) would be unnecessary.

One-step method for catheterising the jugular vein of cats to enable repeated blood sampling.

A one-step method for catheterising the jugular vein of cats for taking multiple blood samples was developed, with the aid of radiography, to determine an appropriate internal catheter length for adult cats. The effects of multiple blood sampling and heparin flushes on the cats' haematocrit and blood total solids were also assessed. Seven healthy adult cats were used. A total of 128 of 132 (97 per cent) blood samples were collected successfully through a 19 G, 30.5 cm catheter introduced as a central venous catheter and maintained in place during two periods of 48 hours. The haematocrit and total solids were significantly decreased in all the cats, but no clinically significant blood loss or coagulation disorders were observed.

Influence of the Respiratory Cycle on Caudal Vena Cava Diameter Measured by Sonography in Healthy Foals: A Pilot Study.

BACKGROUND: Intravascular volume assessment in foals is challenging. In humans, intravascular volume status is estimated by the caudal vena cava (CVC) collapsibility index (CVC-CI) defined as (CVC diameter at maximum expiration [CVCmax ] - CVC diameter at minimal inspiration [CVCmin ])/CVCmax × 100%. HYPOTHESIS/OBJECTIVES: To determine whether the CVC could be sonographically measured in healthy foals, determine differences in CVCmax and CVCmin , and calculate inter- and intrarater variability between 2 examiners. We hypothesized that the CVC could be measured sonographically at the subxiphoid view and that there would be a difference between CVCmax and CVCmin values. ANIMALS: Sixty privately owned foals <1-month-old. METHODS: Prospective study. A longitudinal subxiphoid sonographic window in standing foals was used. The CVCmax and CVCmin were analyzed by a linear mixed effect model. Inter-rater agreement and intrarater variability were expressed by Bland-Altman and intraclass correlation coefficients, respectively. RESULTS: Measurements were attained from 58 of 60 foals with mean age of 15 ± 7.9 days and mean weight of 75.7 ± 17.7 kg. The CVCmax was significantly different from CVCmin (D = 0.515, SE = 0.031, P < 0.001). Inter-rater agreement of the CVC-CI differed by an average of -0.9% (95% limits of agreement, -12.5 to +10.7%). Intrarater variability of CVCmax was 0.540 and 0.545, of CVCmin was 0.550 and 0.594, and of CVC-CI was 0.894 and 0.853 for observers 1 and 2, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate it is possible to reliably measure the CVC sonographically in healthy foals, and the CVC-CI may prove useful in assessing the intravascular volume status in hypovolemic foals.

Effect of Dexamethasone on Resting Blood Lactate Concentrations in Horses.

BACKGROUND: Blood lactate concentration is a marker of tissue perfusion and helps guide therapeutic interventions in critically ill horses. In both humans and dogs, administration of corticosteroids can increase blood lactate concentration, leading to type B hyperlactatemia. This effect could be a consequence of the impact of corticosteroids on glucose metabolism. OBJECTIVES: To investigate the effects of daily IM dexamethasone administration on blood lactate and glucose concentrations in horses. ANIMALS: Nine healthy adult horses. METHODS: A randomized, blinded, controlled, cross-over study design was used. Horses were randomly assigned to 1 of 2 groups, either receiving 0.05 mg/kg of dexamethasone IM or an equivalent volume of saline, daily for 7 days. Blood was collected to determine lactate and glucose concentrations at baseline, 2 hours after the daily injections and 24 hours after the last injection. RESULTS: Dexamethasone treatment had a statistically significant effect on lactate (P = .006) and glucose (P = .033) concentrations. The least squares mean lactate concentration was 0.93 mmol/L (95% CI: 0.87-0.99) in the dexamethasone group compared to 0.71 mmol/L (95% CI: 0.70-0.73) for the saline group. A positive relationship between blood lactate and glucose concentrations was identified, with a 0.07 mmol/L (95% CI: 0.05-0.09) increase in lactate concentration per unit increase in glucose (P < .0001) concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Dexamethasone induces statistically significant increases in blood lactate and glucose concentrations in healthy horses. Awareness of the potential for corticosteroids to induce type B hyperlactatemia might be important in the management of critically ill horses receiving dexamethasone.

Sound Pressure Levels in 2 Veterinary Intensive Care Units.

BACKGROUND: Intensive care units (ICUs) in human hospitals are consistently noisy environments with sound levels sufficient to substantially decrease sleep quality. Sound levels in veterinary ICUs have not been studied previously, but environmental sound has been shown to alter activity in healthy dogs. HYPOTHESIS: Veterinary ICUs, like those in human medicine, will exceed international guidelines for hospital noise. ANIMALS: NA. METHODS: Prospective, observational study performed consecutively and simultaneously over 4 weeks in 2 veterinary ICUs. Conventional A-weighted sound pressure levels (equivalent continuous level [a reflection of average sound], the sound level that is exceeded 90% of the recording period time [reflective of background noise], and maximum sound levels) were continuously recorded and the number of spikes in sound >80 dBA were manually counted. RESULTS: Noise levels were comparable to ICUs in human hospitals. The equivalent continuous sound level was higher in ICU1 than in ICU2 at every time point compared, with greatest differences observed on week day (ICU1, 60.1 ± 3.7 dBA; ICU2, 55.9 ± 2.5 dBA, P < .001) and weekend nights (ICU1, 59.9 ± 2.4 dBA; ICU2, 53.4 ± 1.7 dBA, P < .0001) reflecting a 50% difference in loudness. Similar patterns were observed for the maximum and background noise levels. The number of sound spikes was up to 4 times higher in ICU1 (162.3 ± 84.9 spikes) than in ICU2 (40.4 ± 12.2 spikes, P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: These findings show that sound in veterinary ICUs is loud enough to potentially disrupt sleep in critically ill veterinary patients.

Specificity of the cardiac response to conspecific vocalization in chimpanzees.

Heart rate measures were used to examine the functional response of young chimpanzees and orangutans to acoustic stimuli, including white noise and chimpanzee vocalizations (threat, stress, and alarm). The initial response of the animals to all stimuli was characterized by a prominent cardiac deceleration and an increase in heart period variability. The deceleratory responses persisted with repeated presentations of the noise, stress, and alarm stimuli. In contrast, the response of chimpanzees to the conspecific threat stimulus reverted over trials to a notable cardiac acceleration. This acceleratory response was not attributable to potential patterns of evoked somatic responses. The features of the cardiac response, together with the results of frequency-domain analyses of heart period variability, suggest that this acceleratory response was consistent with the evocation of an aversive or a defensive reaction characterized by sympathetic activation. This pattern of cardiac response appeared early in ontogeny (within 48 hr postnatally) and was not manifest in orangutans. Taken together, the results suggest the existence of specialized perceptual processing mechanisms for vocal stimuli in the chimpanzee. Further examination of these mechanisms may contribute to our understanding of central perceptual processes and the evolution of vocal communication.

Cardiac startle and orienting responses in the great apes.

Cardiac patterns of startle and orienting in response to auditory and vibrotactile stimuli were investigated in the infant chimpanzee and gorilla. Results revealed a notable cardiac acceleration in response to the initial presentations of stimuli of either modality. This acceleratory response appeared to reflect the cardiac correlate of startle and was closely associated with the elicitation of somatic startle responses. This initial cardiac acceleration was subject to rapid habituation and was replaced on subsequent trials by cardiac deceleration, which appeared to reflect the orienting response. Results from the chimpanzees and the gorilla were similar, although a slower rate of habituation was apparent in the gorilla. Taken together, these results are highly consistent with those obtained from humans and monkeys, and they provide the first characterization of cardiac patterns associated with startle and orienting responses in the great apes.

Neurobehavioral organization and the cardinal principle of evaluative bivalence.

The principle of evaluative bivalence asserts that behavioral processes often organize along the evaluative dimension, due to a fundamental pattern of bivalent neurobehavioral organization extending throughout the neuraxis. This principle offers a powerful approach to the explication of complex behavioral relationships and the integration of diverse literatures. It also offers a guiding conceptual framework for the study of neurobehavioral relationships which holds the promise of integrating rather than diversifying the study of neural mechanisms for disparate behavioral phenomena.

Responses to quantity: perceptual versus cognitive mechanisms in chimpanzees (Pan troglodytes).

Two chimpanzees were trained to select among 2 different amounts of candy (1-6 items). The task was designed so that selection of either array by the active (selector) chimpanzee resulted in that array being given to the passive (observer) animal, with the remaining (nonselected) array going to the selector. Neither animal was able to select consistently the smaller array, which would reap the larger reward. Rather, both animals preferentially selected the larger array, thereby receiving the smaller number of reinforcers. When Arabic numerals were substituted for the food arrays, however, the selector animal evidenced more optimal performance, immediately selecting the smaller numeral and thus receiving the larger reward. These findings suggest that a basic predisposition to respond to the perceptual-motivational features of incentive stimuli can interfere with task performance and that this interference can be overridden when abstract symbols serve as choice stimuli.

Language-naive chimpanzees (Pan troglodytes) judge relations between relations in a conceptual matching-to-sample task.

Three chimpanzees with a history of conditional and numeric token training spontaneously matched relations between relations under conditions of nondifferential reinforcement. Heretofore, this conceptual ability was demonstrated only in language-trained chimpanzees. The performance levels of the language-naive animals in this study, however, were equivalent to those of a 4th animal--Sarah--whose history included language training and analogical problem solving. There was no evidence that associative factors mediated successful performance in any of the animals. Prior claims of a profound disparity between language-trained and language-naive chimpanzees apparently can be attributed to prior experience with arbitrary tokens consistently associated with abstract relations and not language per se.

Quantity-based interference and symbolic representations in chimpanzees (Pan troglodytes).

Five chimpanzees with training in counting and numerical skills selected between 2 arrays of different amounts of candy or 2 Arabic numerals. A reversed reinforcement contingency was in effect, in which the selected array was removed and the subject received the nonselected candies (or the number of candies represented by the nonselected Arabic numeral). Animals were unable to maximize reward by selecting the smaller array when candies were used as array elements. When Arabic numerals were substituted for the candy arrays, all animals showed an immediate shift to a more optimal response strategy of selecting the smaller numeral, thereby receiving the larger reward. Results suggest that a response disposition to the high-incentive candy stimuli introduced a powerful interference effect on performance, which was effectively overridden by the use of symbolic representations.

Cardiac correlates of individual recognition in the chimpanzee (Pan troglodytes).

The ability of a chimpanzee to recognize individuals depicted in photographs was evaluated through the use of heart rate measures. Heart rate was recorded before and during photographic projections of human caregivers, familiar individuals, strangers, and blank control slides. In the absence of explicit training or reinforcement, the chimpanzee displayed a differential pattern of heart rate response to the stimulus categories. Although heart rate responses to all stimuli were predominantly deceleratory, the photographs of caregivers yielded consistently larger responses than other stimuli. Results indicate that the chimpanzee is able to recognize individual humans from novel photographic representations and that heart rate can provide an objective measure of such recognition.

The effect of response contingencies on scale model task performance by chimpanzees (Pan troglodytes).

The effects of modified procedures on chimpanzees' (Pan troglodytes) performance in a scale model comprehension task were examined. Seven chimpanzees that previously participated in a task in which they searched an enclosure for a hidden item after watching an experimenter hide a miniature item in the analogous location in a scale model were retested under procedures incorporating response costs. In Experiment 1, chimpanzees were trained under procedures that rewarded only item retrievals occurring on the 1st search attempt. During test trials, 6 chimpanzees performed above chance, including 4 that were previously unsuccessful under the original procedures (V. A. Kuhlmeier, S. T. Boysen, & K. L. Mukobi, 1999). Experiment 2 compared performance under the new and original procedures. Results indicated that for some chimpanzees, performance depended on procedures that decreased the use of competing search strategies and encouraged strategies based on information from the scale model.

Numerical competence in a chimpanzee (Pan troglodytes).

A chimpanzee (Pan troglodytes), trained to count foods and objects by using Arabic numbers, demonstrated the ability to sum arrays of 0-4 food items placed in 2 of 3 possible sites. To address representational use of numbers, we next baited sites with Arabic numbers as stimuli. In both cases performance was significantly above chance from the first sessions, which suggests that without explicit training in combining arrays, the animal was able to select the correct arithmetic sum for arrays of foods or Arabic numbers under novel test conditions. These findings demonstrate that counting strategies and the representational use of numbers lie within the cognitive domain of the chimpanzee and compare favorably with the spontaneous use of addition algorithms demonstrated in preschool children.

Conspecific recognition in the chimpanzee (Pan troglodytes): cardiac responses to significant others.

The ability of a chimpanzee (Pan troglodytes) to recognize photographs of conspecifics was evaluated with heart-rate measures. Heart rate was recorded before, during, and after viewing photographs of an aggressive chimpanzee, a friendly companion animal, and an unfamiliar chimpanzee. The subject displayed a differential pattern of heart-rate response to the stimulus animals, without prior experience with the photographs. Responses to the aggressive animal were acceleratory, which suggests a defensive response. Respiratory sinus arrhythmia suggested that this response was associated with sympathetic activation. In contrast, responses to the familiar animal were minimal, whereas cardiac deceleration was observed in response to the strange chimp, which likely reflects an orienting response. Results suggest the chimpanzee is able to recognize photographs of individual conspecifics and that heart-rate change can reflect the nature of established social relationships between chimpanzees.

Spontaneous discrimination of natural stimuli by chimpanzees (Pan troglodytes).

Six chimpanzees (Pan troglodytes) were presented with pairs of color photographic images of 5 different categories of animals (cat, chimp, gorilla, tiger, fish). The subjects responded to each pair using symbols for "same" and "different." Both within- and between-category discriminations were tested, and all chimpanzees classified the image pairs in accordance with the 5 experimenter-defined categories under conditions of nondifferential reinforcement. Although previous studies have demonstrated identification or discrimination of natural categories by nonhuman animals, subjects were typically differentially reinforced for their responses. The present findings demonstrate that chimpanzees can classify natural objects spontaneously and that such classifications may be similar to those that would be observed in human subjects.