Biochemistry of smooth muscle myosin light chain kinase.

The smooth muscle isoform of myosin light chain kinase (MLCK) is a Ca(2+)-calmodulin-activated kinase that is found in many tissues. It is particularly important for regulating smooth muscle contraction by phosphorylation of myosin. This review summarizes selected aspects of recent biochemical work on MLCK that pertains to its function in smooth muscle. In general, the focus of the review is on new findings, unresolved issues, and areas with the potential for high physiological significance that need further study. The review includes a concise summary of the structure, substrates, and enzyme activity, followed by a discussion of the factors that may limit the effective activity of MLCK in the muscle. The interactions of each of the many domains of MLCK with the proteins of the contractile apparatus, and the multi-domain interactions of MLCK that may control its behaviors in the cell are summarized. Finally, new in vitro approaches to studying the mechanism of phosphorylation of myosin are introduced.

Aiming for a holistic integrated service for men diagnosed with prostate cancer - Definitions of standards and skill sets for nurses and allied healthcare professionals.

PURPOSE: To establish a comprehensive set of recommendations for the service structure and skill set of nurses and allied healthcare professionals in prostate cancer care. METHODS: Using components of formal consensus methodology, a 30-member multidisciplinary panel produced 53 items for discussion relating to the provision of care for prostate cancer patients by specialist nurses and allied healthcare professionals. Items were developed by two rounds of email correspondence in which, first, items were generated and, second, items refined to form the basis of a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. RESULTS: The panel agreed on 33 items that were appropriate for recommendations to be made. These items were grouped under categories of "Environment" and "Patient Pathway" and included comments on training, leadership, communication and quality assessment as well as specific items related to prostate diagnosis clinics, radical treatment clinics and follow-up survivor groups. CONCLUSIONS: Specialist nurses and allied healthcare professionals play a vital role alongside urologists and oncologists to provide care to men with prostate cancer and their families. We present a set of standards and consensus recommendations for the roles and skill-set required for these practitioners to provide gold-standard prostate cancer care. These recommendations could form the basis for development of comprehensive integrated prostate cancer pathways in prostate cancer centres as well as providing guidance for any units treating men with prostate cancer.

Impairments in local heat loss in type 1 diabetes during exercise in the heat.

UNLABELLED: Studies show that vasomotor and sudomotor activities are compromised in individuals with Type 1 diabetes mellitus (T1DM), which could lead to impaired skin blood flow (SkBF) and sweating during heat stress. However, recent work suggests the impairments may only be evidenced beyond a certain level of heat stress. PURPOSE: We examined T1DM-related differences in heat loss responses of SkBF and sweating during exercise performed at progressive increases in the requirement for heat loss. METHODS: Sixteen adults (10 males and six females) with (T1DM, n = 8) and without T1DM (control, n = 8) matched for age, sex, body surface area, and fitness cycled at fixed rates of metabolic heat production of 200, 250, and 300 W·m in the heat (35°C and 20% relative humidity). Each rate was performed sequentially for 30 min. Local sweat rate (LSR, ventilated capsule), sweat gland activation (modified iodine paper technique), and sweat gland output were measured on the forearm, upper back, and chest, whereas SkBF (laser Doppler) was measured on the forearm and upper back. RESULTS: Despite a similar requirement for heat loss, LSR was lower in T1DM on the forearm and chest relative to that in the control. Reductions were measured in the second (forearm: 0.68 ± 0.14 vs 0.85 ± 0.11 mg·min·cm, P = 0.004; chest: 0.58 ± 0.08 vs 0.82 ± 0.12 mg·min·cm, P = 0.046) and third exercise bouts (forearm: 0.75 ± 0.11 vs 0.98 ± 0.12 mg·min·cm, P = 0.005; chest: 0.66 ± 0.1 vs 1.02 ± 0.16 mg·min·cm, P = 0.032). Differences in forearm LSR were the result of a reduction in sweat gland output, whereas the decrease in chest LSR was due to lower sweat gland activation. SkBF did not differ between groups. CONCLUSIONS: We show that T1DM is associated with impairments in heat dissipation during exercise in the heat, as evidenced by attenuated LSR. However, these differences are only shown beyond a certain requirement for heat loss.

Water immersion in the treatment of exertional hyperthermia: physical determinants.

PURPOSE: We examined the effect of differences in body surface area-to-lean body mass ratio (AD/LBM) on core temperature cooling rates during cold water immersion (CWI, 2°C) and temperate water immersion (TWI, 26°C) after exercise-induced hyperthermia. METHODS: Twenty male participants were divided into two groups: high (315.6 ± 7.9 cm·kg, n = 10) and low (275.6 ± 8.6 cm·kg, n = 10) AD/LBM. On two separate occasions, participants ran on a treadmill in the heat (40.0°C, 20% relative humidity) wearing an impermeable rain suit until rectal temperature reached 40.0°C. After exercise, participants were immersed up to the nipples (arms remained out of the water) in either a CWI (2°C) or a TWI (26°C) circulated water bath until rectal temperature returned to 37.5°C. RESULTS: Overall rectal cooling rates were significantly different between experimental groups (high vs low AD/LBM, P = 0.005) and between immersion conditions (CWI vs TWI, P < 0.001). Individuals with a high AD/LBM had an approximately 1.7-fold greater overall rectal cooling rate relative to those with low AD/LBM during both CWI (high: 0.27°C·min ± 0.10°C·min vs low: 0.16°C·min ± 0.10°C·min) and TWI (high: 0.10°C·min ± 0.05°C·min vs low: 0.06°C·min ± 0.02°C·min). Further, the overall rectal cooling rates during CWI were approximately 2.7-fold greater than during TWI for both the high (CWI: 0.27°C·min ± 0.10°C·min vs TWI: 0.10°C·min ± 0.05°C·min) and the low (CWI: 0.16°C·min ± 0.10°C·min vs TWI: 0.06°C·min ± 0.02°C·min) AD/LBM groups. CONCLUSION: We show that individuals with a low AD/LBM have a reduced rectal cooling rate and take longer to cool than those with a high AD/LBM during both CWI and TWI. However, CWI provides the most effective cooling treatment irrespective of physical differences.