Novel isosorbide-based substrates for human butyrylcholinesterase.

Butyrylcholinesterase [EC 3.1.1.8] present widely in mammalian tissue does not have a precisely defined biological function or known endogenous substrate. However, it plays an important role in the detoxification of certain xenobiotics and is an established vector for the systemic liberation of other drugs from their prodrugs. While investigating a series of isosorbide-based prodrugs, we discovered that BuChE catalyses the hydrolysis of esters of the simple sugar isosorbide with unusually rapidity and in some cases with remarkable regioselectivity. In this study, a series of isosorbide esters were synthesised and their rates of hydrolysis measured by HPLC following incubation in diluted plasma solution. In general, little hydrolysis of the 5-ester group could be observed but the 2-ester group was usually hydrolysed very rapidly and the hydrolysis rate exhibited an unusual dependence on the identity of the 5-group. The results indicate that while the 5-ester group is not itself hydrolysed it is important for productive binding in isosorbide diesters.

Beyond U(crit): matching swimming performance tests to the physiological ecology of the animal, including a new fish 'drag strip'.

Locomotor performance of animals is of considerable interest from management, physiological, ecological and evolutionary perspectives. Yet, despite the extensive commercial exploitation of fishes and interest in the health of various fish stocks, the relationships between performance capacity, natural selection, ecology and physiology are poorly known for fishes. One reason may be the technical challenges faced when trying to measure various locomotor capacities in aquatic species, but we will argue that the slow pace of developing new species-appropriate swim tests is also hindering progress. A technique developed for anadromous salmonids (the U(crit) procedure) has dominated the fish exercise physiology field and, while accounting for major advances in the field, has often been used arbitrarily. Here we propose criteria swimming tests should adhere to and report on several attempts to match swimming tests to the physiological ecology of the animal. Sprint performance measured with a laser diode/photocell timed 'drag strip' is a new method employing new technology and is reported on in some detail. A second new test involves accelerating water past the fish at a constant rate in a traditional swim tunnel/respirometer. These two performance tests were designed to better understand the biology of a bentho-pelagic marine fish, the Atlantic cod (Gadus morhua). Finally, we report on a modified incremental velocity test that was developed to better understand the biology of the blacknose dace (Rhinichthys atratulus), a Nearctic, lotic cyprinid.

High-altitude acclimation increases the triacylglycerol/fatty acid cycle at rest and during exercise.

High-altitude acclimation alters lipid metabolism during exercise, but it is unknown whether this involves changes in rates of lipolysis or reesterification, which form the triacylglycerol/fatty acid (TAG/FA) cycle. We combined indirect calorimetry with [2-(3)H]glycerol and [1-(14)C]palmitate infusions to simultaneously measure total lipid oxidation, lipolysis, and rate of appearance (R(a)) of nonesterified fatty acids (NEFA) in high-altitude-acclimated (HA) rats exercising at 60% maximal O(2) uptake (VO(2 max)). During exercise, relative total lipid oxidation (%VO(2)) equaled sea-level control (SL) values; however, acclimation greatly stimulated lipolysis (+75%) but had no effect on R(a) NEFA. As a result, TAG/FA cycling increased (+119%), due solely to an increase in recycling (+144%) within adipocytes. There was no change in either group in these variables with the transition from rest to exercise. We conclude that, in HA, 1) acclimation is a potent stimulator of lipolysis; 2) rats do not modify TAG/FA cycling with the transition to exercise; and 3) in normoxia, HA and SL derive the same fraction of their total energy from lipids and carbohydrates.

Leptin: an essential regulator of lipid metabolism.

This paper reviews the general mechanisms by which leptin acts as a regulator of lipid reserves through changes in food intake, energy expenditure and fuel selection, with an emphasis on its direct effects on cellular lipid metabolism. Briefly, when leptin levels increase, food consumption decreases via modulation of hypothalamic neuropeptides. As well, normal decreases in energy expenditures (e.g. with diurnal cycles or reduced caloric intake) do not occur. This is probably caused by an increase in mitochondrial proton leak mediated by leptin via increases in sympathetic nervous system stimulation and thyroid hormone release. The decrease in caloric input coupled with relatively higher energy expenditure, therefore, leads to negative energy balance. Leptin also changes the fuel source from which ATP is generated. Fuel preference switches from carbohydrate (glucose) to lipid (fatty acids). This effect arises through stimulation of triacylglycerol catabolism by leptin. In vitro studies show that leptin is a potent stimulator of lipolysis and fatty acid oxidation in adipocytes and other cell types. Consequently, leptin is also a regulator of cellular triacylglycerol content. Hormonal regulation of leptin, as well as its role in fasting and seasonal weight gain and energy expenditure are also briefly discussed.

Aerobic and anaerobic swimming performance of individual Atlantic cod.

Individual Atlantic cod (Gadus morhua) were exercised using three different measures of swimming performance. (1) An endurance test (critical swimming speed, U(crit), protocol) designed to assess predominantly aerobic endurance swimming (duration hours). (2) An acceleration test (U(burst)), in which the fish were required to swim against a rapidly increasing current until exhausted (duration minutes). This test was designed to assess predominantly glycolytic-based swimming capacity. (3) A sprint test that examined the animals' ability to swim away from a sudden stimulus (duration seconds). Rates of oxygen consumption ( mdot (O2)) during the endurance test and various morphological variables of the individual fish were also measured. Both aerobic and anaerobic swimming performance of individual cod were found to be significantly repeatable over a 3 month period. mdot (O2) during the U(crit) protocol was also significantly repeatable at intermediate to high swimming speeds, but not at low speeds. Our results support extrapolation from metabolic rates at incremented swimming speeds to zero activity as the best way to measure standard metabolic rate in cod. While performance in the U(crit) test and the sprint test were positively correlated, there was a negative correlation between performance in the U(crit) test and performance in the U(burst) test. This implies a potential trade-off in individual cod between stamina and the ability to use glycolytic-based locomotion. Inter-individual variation in swimming performance during these protocols, while substantial, was not correlated with individual variation in fin surface areas, age or morphology. However, U(burst) performance was dependent upon the sex of the animals, while performance during the U(crit) protocol was significantly correlated with their aerobic scope for activity.

Overview of pediatric arrhythmias.

Cardiac arrhythmias are being depressed with increased frequency in the pediatric population. Causes of pediatric arrhythmias in the general population include severe metabolic or electrolyte disturbances, drug toxicity, and chest trauma. Repairs of complex congenital heart disease have frequently left this population with persistent or recurrent postoperative arrhythmias. The diagnosis, evaluation, and management of pediatric arrhythmias requires nurses to be skilled in hemodynamic assessment and arrhythmia detection. The registered nurse's grasp of developmental issues and family education is vital in providing quality care to families dealing with these diagnoses.

Streptokinase use in children undergoing cardiac catheterization.

The development of cardiac catheterization procedures in the pediatric population has evolved from diagnostic in nature to present day advanced technology and interventions. A complication of vessel occlusion secondary to large catheters, length of procedures, and patient size requires immediate intervention. The advent of thrombolytic agents has provided a highly effective mode of treatment in restoring circulation. The use of streptokinase, its efficacy, side effects, and nursing management are discussed.