An investigation of symptom-specific muscle hyperreactivity in upper extremity cumulative trauma disorder

Objective: The study examined symptom-specific muscle hyperreactivity in patients with chronic pain with upper limb cumulative trauma disorder (CTD). Design: Four tasks were presented in counterbalanced order and included neutral, general stressor, personal stressor, and pain stressor tasks. Ratings of stressfulness and recordings of skin conductance level confirmed the effectiveness of the experimental manipulations in inducing stress experiences for all subject groups. Setting: The study was conducted in a university research center. Patients: Thirty patients with CTD were matched as closely as possible for age and gender to control groups of chronic low back pain, arthritis, and pain-Free subjects Outcome Measures: Surface electromyograph recordings were taken from the frontalis, forearm flexors, trapezius, and lower back during baseline and tasks. Results: The study found no evidence of greater muscle tension increases or extended duration of return to baseline for the CTD or low back pain patients at any of the muscle sites for any of the tasks in comparison to control groups. Conclusions: The results indicate that symptom-specific psychophysiological responses may be limited to certain subgroups rather than being characteristic of chronic musculoskeletal pain patients in general.

Controlled partial mine ventiliation recirculation trial at Mount Isa Mines

The ventilation and cooling of deep, hot mines present particular problems in Australia as a consequence of the surface climate, the size of the underground voids, the degree of mechanization and the cost of power in remote areas. A preliminary investigation of the effects of controlled partial recirculation of air was conducted in Mount Isa Mines' Deep Copper section. Gas and dust concentrations were measured in the exhaust air of the major working section to assess the potential for recirculating exhaust air to the intake airways to reduce the cost of providing an acceptable working environment in the deep parts of the mine. Studies were undertaken of airborne dust deposition in vertical airways and the efficiency of usage of the ventilation air in diluting contaminants. It was established that 45% of the respirable dust was deposited in a 130-m vertical raise and 60% of the air supplied to the section could be reused or recirculated. The first major field trial of a controlled partial recirculation system in Australia was undertaken in the light of these results and demonstrated excellent potential for significant reduction in ventilation costs. Gas and dust contaminant levels were well below the threshold limit values during the trial. It is concluded that controlled partial recirculation can be a practical, effective and safe aid to normal ventilation practice in Australian deep, hot mines.

A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal human sera

CD83 is an inducible glycoprotein expressed predominantly by dendritic cells (DC) and B lymphocytes. Expression of membrane CD83 (mCD83) is widely used as a marker of differentiated/ activated DC but its function and ligand(s) are presently unknown. We report the existence of a soluble form of CD83 (sCD83). Using both a sCD83-specific ELISA and Western blotting, we could demonstrate the release of sCD83 by mCD83(+) B cell and Hodgkin's disease-derived cell lines, but not mCD83(-) cells. Inhibition of de novo protein synthesis did not affect the release of sCD83 during short-term (2 h) culture of cell lines although mCD83 expression was significantly reduced, suggesting sCD83 is generated by the release of mCD83. Isolated tonsillar B lymphocytes and monocyte-derived DC, which are mCD83(low), released only low levels of sCD83 during culture. However, the differentiation/activation of these populations both up-regulated mCD83 and increased sCD83 release significantly. Analysis of sera from normal donors demonstrated the presence of low levels (121 +/- 3.6 pg/ml) of circulating sCD83. Further studies utilizing purified sCD83 and the analysis of sCD83 levels in disease may provide clues to the function and ligand(s) of CD83.

The plausibility of long-wavelength stress correlation or stress magnitude as a mechanism for precursory seismicity: Results from two simple elastic models

Observations of accelerating seismic activity prior to large earthquakes in natural fault systems have raised hopes for intermediate-term eartquake forecasting. If this phenomena does exist, then what causes it to occur? Recent theoretical work suggests that the accelerating seismic release sequence is a symptom of increasing long-wavelength stress correlation in the fault region. A more traditional explanation, based on Reid's elastic rebound theory, argues that an accelerating sequence of seismic energy release could be a consequence of increasing stress in a fault system whose stress moment release is dominated by large events. Both of these theories are examined using two discrete models of seismicity: a Burridge-Knopoff block-slider model and an elastic continuum based model. Both models display an accelerating release of seismic energy prior to large simulated earthquakes. In both models there is a correlation between the rate of seismic energy release with the total root-mean-squared stress and the level of long-wavelength stress correlation. Furthermore, both models exhibit a systematic increase in the number of large events at high stress and high long-wavelength stress correlation levels. These results suggest that either explanation is plausible for the accelerating moment release in the models examined. A statistical model based on the Burridge-Knopoff block-slider is constructed which indicates that stress alone is sufficient to produce accelerating release of seismic energy with time prior to a large earthquake.

The linker domain of the Ha-Ras hypervariable region regulates interactions with exchange factors, Raf-1 and phosphoinositide 3-kinase

Ha-Ras and Ki-Ras have different distributions across plasma membrane microdomains. The Ras C-terminal anchors are primarily responsible for membrane microlocalization, but recent work has shown that the interaction of Ha-Ras with lipid rafts is modulated by GTP loading via a mechanism that requires the hypervariable region (HVR). We have now identified two regions in the HVR linker domain that regulate Ha-Ras raft association. Release of activated Ha-Ras from lipid rafts is blocked by deleting amino acids 173-179 or 166-172. Alanine replacement of amino acids 173-179 but not 166-172 restores wild type micro-localization, indicating that specific N-terminal sequences of the linker domain operate in concert with a more C-terminal spacer domain to regulate Ha-Ras raft association. Mutations in the linker domain that confine activated Ha-RasG12V to lipid rafts abrogate Raf-1, phosphoinositide 3-kinase, and Akt activation and inhibit PC 12 cell differentiation. N-Myristoylation also prevents the release of activated Ha-Ras from lipid rafts and inhibits Raf-1 activation. These results demonstrate that the correct modulation of Ha-Ras lateral segregation is critical for downstream signaling. Mutations in the linker domain also suppress the dominant negative phenotype of Ha-RasS17N, indicating that HVR sequences are essential for efficient interaction of Ha-Ras with exchange factors in intact cells.

Effect of aestivation on muscle characteristics and locomotor performance in the Green-striped burrowing frog, Cyclorana alboguttata

The Green-striped burrowing frog. Cyclorana alboguttata survives extended drought periods by burrowing underground and aestivating. These frogs remain immobile within cocoons of shed skin and Mucus during aestivation and emerge from their burrows upon heavy rains to feed and reproduce. Extended periods of immobilisation in mammals typically result in muscle atrophy and a decrease in muscle performance. We examined the effect of aestivation and hence prolonged immobilisation, on skeletal Muscle mass. in vitro muscle performance, and locomotor performance in C. alboguttata. Frogs were aestivated in soil for 3 months and were compared with control animals that remained active, were fed, and had a continual supply of water. Compared to the controls, the wet mass of the gastrocnemius. sartorius, gracilus major. semimembranosus. peroneus, extensor cruris, tibialis posticus and tibialis anticus longus of aestivators remained unchanged indicating no muscle atrophy. The in-vitro performance characteristics of the gastroenemius muscle were maintained and burst swimming speed Was Unaffected, requiring no recovery from the extended period of immobilisation associated with aestivation. This preservation of muscle size, contractile condition and locomotor performance through aestivation enables C. alboguttata to compress their life history into unpredictable windows of opportunity, whenever heavy rains occur.

Maintaining muscle mass during extended disuse: Aestivating frogs as a model species

Prolonged muscle disuse in vertebrates can lead to a pathological change resulting in muscle wasting and a loss of muscle strength. In this paper, we review muscle disuse atrophy in the vertebrates and examine the factors that influence the magnitude of the atrophic response during extended periods of inactivity, both artificially imposed (e.g. limb immobilisation) and naturally occurring, such as the quiescence associated with dormancy (e.g. hibernation and aestivation). The severity of muscle atrophy is positively correlated with mass-specific metabolic rate, and the metabolic depression that occurs during dormancy would appear to have a protective role, reducing or preventing muscle atrophy despite periods of inactivity lasting 6-9 months. In the light of these findings, the role of reactive oxygen species and antioxidants during muscle disuse is emphasised.

Factors affecting the establishment and dispersal of nymphs of Pristhesancus plagipennis Walker (Hemiptera : Reduviidae) when released onto soybean, cotton and sunflower crops

A problem with augmenting predatory bugs through mass release is the logistical difficulty of delivering nymphs onto the foliage of field crops. In this paper we examine postrelease establishment and dispersal of the nymphs of the predatory bug Pristhesancus plagipennis on soybean, cotton and sunflower in an effort to devise an appropriate strategy for field release. The effects of predator stadia and release rates on field establishment and within-crop-canopy dispersal after hand release were recorded in soybean, cotton and sunflower. Field establishment improved with the release of more-developed nymphs, with third instars providing the most appropriate compromise between field hardiness and rearing cost. Increased nymphal density at the point of release had little effect on nymphal dispersal throughout the crop canopy. The patterns of nymphal dispersal observed on the three crops suggest that crop-canopy architecture may have an effect on the ability of nymphs to spread out postrelease, as nymphs dispersed poorly in cotton and sunflower compared to soybean. To overcome poor dispersal of nymphs after release, a mechanical release method, where nymphs were mixed with vermiculite and delivered onto a target crop through a spinning disk fertiliser spreader, was tested, and provided similar nymph establishment rates and dispersal patterns as releasing nymphs individually by hand. The implications of nymph dispersal and field hardiness in regard to inundative field release techniques are discussed.

A comparison of peak power in the shoulder press and shoulder throw

The ability to generate peak power is central for performance in many sports. Currently two distinct resistance training methods are used to develop peak power, the heavy weight/slow velocity and light weight/fast velocity regimes. When using the light weight/fast velocity power training method it was proposed that peak power would be greater in a shoulder throw exercise compared with a normal shoulder press. Nine males performed three lifts in the shoulder press and shoulder throw at 30% and 40% of their one repetition maximum (1RM). These lifts were performed identically, except for the release of the bar in the throw condition. A potentiometer attached to the bar measured displacement and duration of the lifts. The time of bar release in the shoulder throw was determined with a pressure switch. ANOVA was used to examine statistically significant differences where the level of acceptance was set at p

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity: possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

Control of ovulation with a GnRH agonist after superstimulation of follicular growth in buffalo: fertilization and embryo recovery

The potential to use a GnRH agonist bioimplant and injection of exogenous LH to control the time of ovulation in a multiple ovulation and embryo transfer (MOET) protocol was examined in buffalo. Mixed-parity buffalo (Bubalus bubalis; 4-15-year-old; 529 13 kg LW) were randomly assigned to one of five groups (n = 6): Group 1, conventional MOET protocol; Group 2, conventional MOET with 12 It delay in injection of PGF(2alpha); Group 3, implanted with GnRH agonist to block the pre-ovulatory surge release of LH; Group 4, implanted with GnRH agonist and injected with exogenous LH (Lutropin(R), 25 mg) 24 h after 4 days of superstimulation with FSH; Group 5, implanted with GnRH agonist and injected with LH 36 h after superstimulation with FSH. Ovarian follicular growth in all buffaloes was stimulated by treatment with FSH (Folltropin-V(R), 200 mg) administered over 4 days, and was monitored by ovarian ultrasonography. At the time of estrus, the number of follicles greater than or equal to8 mm. was greater (P < 0.05) for buffaloes in Group 2 (12.8) than for buffaloes in Groups 1 (8.5), 3 (7.3), 4 (6.1) and 5 (6.8), which did not differ. All buffaloes were mated by AI after spontaneous (Groups 1-3) or induced (Groups 4 and 5) ovulation. The respective number of buffalo that ovulated, number of corpora lutea, ovulation rate (%), and embryos + oocytes recovered were: Group 1 (2, 1.8 +/- 1.6, 18.0 +/- 13.6, 0.2 +/- 0.2); Group 2 (4, 6.1 +/- 2.9, 40.5 +/- 17.5, 3.7 +/- 2.1); Group 3 (0, 0, 0, 0); Group 4 (6, 4.3 +/- 1.2, 69.3 +/- 14.2, 2.0 +/- 0.9); and Group 5 (1, 2.5 +/- 2.5, 15.5 +/- 15.5, 2.1 +/- 2.1). All buffaloes in Group 4 ovulated after injection of LH and had a relatively high ovulation rate (69%) and embryo recovery (46%). It has been shown that the GnRH agonist-LH protocol can be used to improve the efficiency of MOET in buffalo. (C) 2002 Elsevier Science Inc. All rights reserved.

NPS-2143 - Treatment of osteoporosis - Calcilytic

Efforts to discover new treatments for osteoporosis led to the identification of the potent and selective, small-molecule calcium receptor antagonist NPS-2143. NPS-2143 is the prototype calcilytic drug, designed to act on calcium receptors on the surface of parathyroid glands, stimulating the release of the body's own stores of native parathyroid hormone (PTH). In osteopenic ovariectomized rats, daily oral administration of NPS-2143 resulted in moderate but sustained increases in plasma PTH levels and marked increases in bone formation and resorption, with no net bone gain or loss. The combination of NPS-2143 and estrogen increases bone formation and density to a greater extent than either agent alone. These results suggest that NPS-2143 may be useful in the treatment of established osteoporosis.

Present and future pharacotherapy for heart failure

The pharmacotherapy currently recommended by the American College of Cardiology and the American Heart Association for heart failure (HF) is a diuretic, an angiotensin-converting enzyme inhibitor (ACEI), a β-adrenoceptor antagonist and (usually) digitalis. This current treatment of HF may be improved by optimising the dose of ACEI used, as increasing the dose of lisinopril increases its benefits in HF. Selective angiotensin receptor-1 (AT1) antagonists are effective alternatives for those who cannot tolerate ACEIs. AT1 antagonists may also be used in combination with ACEIs, as some studies have shown cumulative benefits for the combination. In addition to being used in Stage IV HF patients, in whom it has a marked benefit, spironolactone should be studied in less severe HF and in the presence of β-blockers. The use of carvedilol, extended-release metoprolol and bisoprolol should be extended to severe HF patients as these agents have been shown to decrease mortality in this group. The ancillary properties of carvedilol, particularly antagonism at prejunctional β-adrenoceptors, may give it additional benefits to selective β1-adrenoceptor antagonists. Celiprolol and bucindolol are not the β-blockers of choice in HF, as they do not decrease mortality. Although digitalis does not reduce mortality, it remains the only option for a long-term positive inotropic effect, as the long-term use of the phosphodiesterase inhibitors is associated with increased mortality. The calcium sensitising drug levosimendan may be useful in the hospital treatment of decompensated HF to increase cardiac output and improve dyspnoea and fatigue. The antiarrhythmic drug amiodarone should probably be used in patients at high risk of arrhythmic or sudden death, although this treatment may soon be superseded by the more expensive implanted cardioverter defibrillators, which are probably more effective and have fewer side effects. The natriuretic peptide nesiritide has recently been introduced for the hospital treatment of decompensated HF. Novel drugs that may be beneficial in the treatment of HF include the vasopeptidase inhibitors and the selective endothelin-A receptor antagonists but these require much more investigation. However, disappointing results have been obtained in a large clinical trial of the tumour necrosis factor α antagonist etanercept, where no likelihood of a difference between placebo and etanercept was observed. Small clinical trials with recombinant growth hormone to thicken ventricles in dilated cardiomyopathy have given variable results.

Activation of ion secretion via proteinase-activated receptor-2 in human colon

Proteinase-activated receptor (PAR) type 2 (PAR-2) has been shown to mediate ion secretion in cultured epithelial cells and rat jejunum. With the use of a microUssing chamber, we demonstrate the role of PAR-2 for ion transport in native human colonic mucosa obtained from 30 normal individuals and 11 cystic fibrosis (CF) patients. Trypsin induced Cl- secretion when added to the basolateral but not luminal side of normal epithelia. Activation of Cl- secretion by trypsin was inhibited by indomethacin and was further increased by cAMP in normal tissues but was not present in CF colon, indicating the requirement of luminal CF transmembrane conductance regulator. Effects of trypsin were largely reduced by low Cl-,by basolateral bumetanide, and in the presence of barium or clotrimazole, but not by tetrodotoxin. Furthermore, trypsin-induced secretion was inhibited by the Ca2+-ATPase inhibitor cyclopiazonic acid and in low-Ca2+ buffer. The effects of trypsin were almost abolished by trypsin inhibitor. Thrombin, an activator of PAR types 1, 3, and 4, had no effects on equivalent short-circuit currents. The presence of PAR-2 in human colon epithelium was confirmed by RT-PCR and additional experiments with PAR-2-activating peptide. PAR-2-mediated intestinal electrolyte secretion by release of mast cell tryptase and potentiation of PAR-2 expression by tumor necrosis factor-alpha may contribute to the hypersecretion observed in inflammatory processes such as chronic inflammatory bowel disease.

Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II

Human R183H-GH causes autosomal dominant GH deficiency type II. Because we show here that the mutant hormone is fully bioactive, we have sought to locate an impairment in its progress through the secretory pathway as assessed by pulse chase experiments. Newly synthesized wild-type and R183H-GH were stable when expressed transiently in AtT20 cells, and both formed equivalent amounts of Lubrol-insoluble aggregates within 40 min after synthesis. There was no evidence for intermolecular disulfide bond formation in aggregates of wild-type hormone or the R183H mutant. Both wildtype and R183H-GH were packaged into secretory granules, assessed by the ability of 1 mm BaCl2 to stimulate release and by immunocytochemistry. The mutant differed from wildtype hormone in its retention in the cells after packaging into secretory granules; 50% more R183H-GH than wild-type aggregates were retained in AtT20 cells 120 min after synthesis, and stimulated release of R183H-GH or a mixture of R183H-GH and wild-type that had been retained in the cell was reduced. The longer retention of R183H-GH aggregates indicates that a single point mutation in a protein contained in secretory granules affects the rate of secretory granule release.