Pharmacokinetics of intravenous lithium chloride and assessment of agreement between two methods of lithium concentration measurement in the horse.

BACKGROUND: Pharmacokinetics of lithium chloride (LiCl) administered as a bolus, once i.v. have not been determined in horses. There is no point-of-care test to measure lithium (Li+ ) concentrations in horses in order to monitor therapeutic levels and avoid toxicity. OBJECTIVES: To determine the pharmacokinetics of LiCl in healthy adult horses and to compare agreement between two methods of plasma Li+ concentration measurement: spectrophotometric enzymatic assay (SEA) and inductively coupled plasma mass spectrometry (ICP-MS). STUDY DESIGN: Nonrandomised, single exposure with repeated measures over time. METHODS: Lithium chloride was administered (0.15 mmol/kg bwt) as an i.v. bolus to eight healthy adult horses. Blood samples were collected pre-administration and at multiple times until 48 h post-administration. Samples were analysed by two methods (SEA and ICP-MS) to determine plasma Li+ concentrations. Pharmacokinetics were determined based on the reference ICP-MS data. RESULTS: Adverse side effects were not observed. The SEA showed linearity, R2 = 0.9752; intraday coefficient of variation, 2.5%; and recovery, 96.3%. Both noncompartmental and compartmental analyses (traditional two-stage and nonlinear mixed-effects [NLME] modelling) were performed. Geometric mean values of noncompartmental parameters were plasma Li+ concentration at time zero, 2.19 mmol/L; terminal elimination half-life, 25.68 h; area under the plasma concentration-time curve from time zero to the limit of quantification, 550 mmol/L min; clearance, 0.273 mL/min/kg; mean residence time, 31.22 h; and volume of distribution at steady state, 511 mL/kg. Results of the traditional two-stage analysis showed good agreement with the NLME modelling approach. Bland-Altman analyses demonstrated poor agreement between the SEA and ICP-MS methods (95% limits of agreement = 0.14 ± 0.13 mmol/L). MAIN LIMITATIONS: Clinical effects of LiCl have not been investigated. CONCLUSIONS: The LiCl i.v. bolus displayed pharmacokinetics similar to those reported in other species. The SEA displayed acceptable precision but did not agree well with the reference method (ICP-MS). The Summary is available in Spanish - see Supporting Information.

Effects of a maternal high-fat diet on offspring behavioral and metabolic parameters in a rodent model.

Maternal diet-induced obesity can cause detrimental developmental origins of health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can lead to later behavioral and metabolic disturbances, but it is not clear which behaviors and metabolic parameters are most vulnerable. To address this critical gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may better replicate most human societies, were used in the current study. About 2 weeks before breeding, adult females were placed on a control or HFD and maintained on the diets throughout gestation and lactation. F1 offspring were placed at weaning (30 days of age) on the control diet and spatial learning and memory, anxiety, exploratory, voluntary physical activity, and metabolic parameters were tested when they reached adulthood (90 days of age). Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes maze trials in male, but not female, offspring. Both male and female HFD-fed offspring showed increased anxiogenic behaviors, but decreased exploratory and voluntary physical activity. Moreover, HFD offspring demonstrated lower resting energy expenditure (EE) compared with controls. Accordingly, HFD offspring weighed more at adulthood than those from control fed dams, likely the result of reduced physical activity and EE. Current findings indicate a maternal HFD may increase obesity susceptibility in offspring due to prenatal programming resulting in reduced physical activity and EE later in life. Further work is needed to determine the underpinning neural and metabolic mechanisms by which a maternal HFD adversely affects neurobehavioral and metabolic pathways in offspring.

Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity.

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol.

BACKGROUND: The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. HYPOTHESIS: Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. ANIMALS: Seven mature, obese ponies. METHODS: Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, i.v.) and insulin (0.1 U/kg, i.v.) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand-held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. RESULTS: Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand-held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT.

Continuous glucose monitoring in dogs and cats.

Use of continuous glucose monitoring in veterinary medicine is gaining popularity. Through use of a commercially available continuous glucose monitor system, insights into daily glucose changes in dogs and cats are achievable. The continuous glucose monitoring system measures glucose concentrations in the interstitial fluid of the subcutaneous space by use of a small, flexible probe. When placed in the subcutaneous tissue, the probe is connected to a recording device that is attached to the animal and records the interstitial fluid glucose concentration every 5 minutes (288 readings per 24 hours). Once attached and properly calibrated, the instrument can remain in place for several days, hospitalization of the patient is not necessary, and the normal daily routine of the animal can be maintained. The data from the recording device are then downloaded and a very detailed picture of the interstitial fluid glucose concentration over that time period can be obtained. Subcutaneous interstitial fluid glucose concentrations have a good correlation to blood glucose concentrations within a defined range. The continuous glucose monitoring system has distinct advantages over traditional blood glucose curves and is a valuable tool for managing diabetic dogs and cats. In addition, other clinical uses for continuous glucose monitoring are being developed. This review is designed to outline the technology behind the continuous glucose monitoring system, describe the clinical use of the instrument, provide clinical examples in which it may be useful, and discuss future directions for continuous glucose monitoring in dogs and cats.