Muscle strength and pressor response.

The purpose of this study was to determine if muscle strength influences the hyperemic response to dynamic exercise. Men with low (n=8) and high (n=9) maximal forearm strength performed dynamic handgrip exercise as the same absolute workload increased in a ramp function (0.5 kg x min (-1)). Forearm blood flow (FBF) was measured instantaneously by ultrasound Doppler and blood pressure was measured by auscultation. The pressor response to exercise was greater (P<0.05) for low strength men at workloads >1.5 kg allowing volumetric FBF (ml x min (-1)) and vascular conductance to increase in proportion to absolute workload similar to high strength men. When FBF was expressed relative to forearm volume (ml x min (-1).100 ml (-1)) the hyperemic response to exercise (slope of relative FBF vs. workload) was greater in low strength men (3.2+/-1.5 vs. 1.7+/-0.4 ml x min (-1).100 ml (-1) x kg (-1), P<0.05) as was relative FBF at workloads >1.5 kg. However, when relative FBF was compared across relative work intensity, no difference was found between low and high strength groups. Together, these findings suggest men with low strength require a greater pressor response to match blood flow to exercise intensity as compared to high strength men.

Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean.

Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial transporter superfamily that is expressed predominantly in skeletal muscle. However, its close relative UCP-1 is expressed exclusively in brown adipose tissue, a tissue whose main function is fat combustion and thermogenesis. Studies on the expression of UCP-3 in animals and humans in different physiological situations support a role for UCP-3 in energy balance and lipid metabolism. However, direct evidence for these roles is lacking. Here we describe the creation of transgenic mice that overexpress human UCP-3 in skeletal muscle. These mice are hyperphagic but weigh less than their wild-type littermates. Magnetic resonance imaging shows a striking reduction in adipose tissue mass. The mice also exhibit lower fasting plasma glucose and insulin levels and an increased glucose clearance rate. This provides evidence that skeletal muscle UCP-3 has the potential to influence metabolic rate and glucose homeostasis in the whole animal.

Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.

Practical and theoretical issues in gene-targeting studies and their application to behaviour.

Some of the major practical and theoretical issues that are associated with gene-targeting studies in mice are discussed. The availability of sufficient space to house the extensive breeding colonies associated with studies in gene-manipulated mice is an important logistical consideration that requires consideration at an early stage. A practical example is discussed which illustrates some of these issues. Problems associated with disease control and methods of maintaining the health status of valuable colonies are also outlined. Differences in the behavioural phenotype of inbred mouse strains pose important issues for study design and selection of host mouse lines. The results from studies exploring variations in the behavioural phenotype of six common inbred strains are briefly outlined. The impact of phenotypic variation on behavioural studies is considered and the implications for experimental design are discussed.

Changes in adrenocortical function with aging and therapeutic implications.

Throughout life, the adrenal cortex exhibits dramatic morphogenic and steroidogenic changes. While there is subtle senescent decline in aldosterone, and a similarly subtle increase in cortisol, the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) decline with age in a situation similar to menopause, and this decline is considered by some to aggravate some age-related diseases. This decline is associated with an almost complete loss of the inner zone of the adrenal cortex, known as the zona reticularis. This review addresses these adrenal cortical changes, and explores their clinical significance. In particular, the clinical data on DHEA replacement in aging is addressed.

Eliminate transcribing on nursing units--a time and money saving new approach to ancillary requisitioning.

Manual systems for requisitioning services are gradually being replaced with data entry terminals on the nursing divisions. These systems claim greater accuracy and timeliness of response, but the capital investment necessary is oftentimes unwarranted, as well as being cost prohibitive for many hospitals.