Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension.

OBJECTIVES: A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). DESIGN: Subjects diagnosed with hypertension (n = 45, age 35-64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15-0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure. RESULTS: Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (ß = -0.25±0.1, P = 0.02), baroreflex sensitivity (ß = -0.33±0.7, P = 0.04) and RR interval (ß = -0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6. CONCLUSIONS: Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Fungal Planet description sheets: 69-91.

Novel species of microfungi described in the present study include the following from Australia: Bagadiella victoriae and Bagadiella koalae on Eucalyptus spp., Catenulostroma eucalyptorum on Eucalyptus laevopinea, Cercospora eremochloae on Eremochloa bimaculata, Devriesia queenslandica on Scaevola taccada, Diaporthe musigena on Musa sp., Diaporthe acaciigena on Acacia retinodes, Leptoxyphium kurandae on Eucalyptus sp., Neofusicoccum grevilleae on Grevillea aurea, Phytophthora fluvialis from water in native bushland, Pseudocercospora cyathicola on Cyathea australis, and Teratosphaeria mareebensis on Eucalyptus sp. Other species include Passalora leptophlebiae on Eucalyptus leptophlebia (Brazil), Exophiala tremulae on Populus tremuloides and Dictyosporium stellatum from submerged wood (Canada), Mycosphaerella valgourgensis on Yucca sp. (France), Sclerostagonospora cycadis on Cycas revoluta (Japan), Rachicladosporium pini on Pinus monophylla (Netherlands), Mycosphaerella wachendorfiae on Wachendorfia thyrsifolia and Diaporthe rhusicola on Rhus pendulina (South Africa). Novel genera of hyphomycetes include Noosia banksiae on Banksia aemula (Australia), Utrechtiana cibiessia on Phragmites australis (Netherlands), and Funbolia dimorpha on blackened stem bark of an unidentified tree (USA). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men.

Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity.

The effects of the 5-HT2C agonist m-chlorophenylpiperazine on elite athletes with unexplained underperformance syndrome (overtraining).

A possible link between the neurotransmitter, 5-hydroxytryptamine (5-HT), plasma tryptophan, and branched chain amino acids concentration and exercise-induced fatigue is described by the central fatigue hypothesis. 5-HT receptors and neuroendocrine "challenge" tests, using prolactin release as an indirect measure of 5-HT activity were studied by recent investigations. In the present study, the original hypothesis about the role of amino acids in increasing brain 5-HT with a neuroendocrine challenge test on elite athletes diagnosed with unexplained, underperformance syndrome (UUPS) was combined. There was an apparent increased sensitivity of 5-HT receptors in athletes with UUPS compared with fit, well-trained controls, as measured via increased prolactin release following a bolus dose of m-chlorophenylpiperazine , a 5-HT agonist. No changes were observed in plasma amino acid concentrations in either group. There is evidence that well-trained athletes have a reduced sensitivity of 5-HT receptors. The present study suggests that this adaptation may be lost in athletes with UUPS: this might explain some of their observed symptoms.

Recombinant human interleukin-6 infusion during low-intensity exercise does not enhance whole body lipolysis or fat oxidation in humans.

The present study examined the role of the cytokine IL-6 in the regulation of fatty acid metabolism during exercise in humans. Six well-trained males completed three trials of 120 min of cycle ergometry at 70% peak O(2) consumption (Vo(2 peak); MOD) and 40% Vo(2 peak) with (LOW + IL-6) and without (LOW) infusion of recombinant human (rh)IL-6. The dose of rhIL-6 during LOW + IL-6 elicited IL-6 concentration similar to those during MOD but without altering the circulating hormonal milieu seen in MOD. Palmitate rate of appearance (R(a)), rate of disappearance (R(d)), and oxidation were measured by means of a constant infusion of [U-(13)C]palmitate (0.015 micromol.kg(-1).min(-1), prime NaHCO(3), 1 micromol/kg). Palmitate R(a), R(d), and oxidation were not affected by rhIL-6 infusion, remaining similar to LOW at all times. Palmitate R(a) and oxidation were significantly greater in the MOD trial (P < 0.05) compared with the LOW + IL-6 and LOW trials. Our data show that a low dose of rhIL-6, administered during low-intensity exercise without altering the hormonal milieu, does not alter fatty acid metabolism. These data suggest that the increase in fatty acid utilization seen during exercise at moderate compared with low intensity is not mediated via alterations in plasma IL-6.

Vascular endothelial growth factor mRNA expression and arteriovenous balance in response to prolonged, submaximal exercise in humans.

Angiogenesis, the growth of new blood vessels from existing ones, occurs in the skeletal muscle as an adaptive response to exercise that satisfies the increased requirement of this tissue for oxygen delivery and metabolic processes. Of the factors that have been identified to regulate this process, the endothelial cell mitogen vascular endothelial growth factor (VEGF) has been proposed to play a key role. The aim of this study was to measure the skeletal muscle VEGF mRNA content and arteriovenous protein balance across the working leg in response to a single bout of prolonged, submaximal exercise. Seven physically active males completed 3 h of two-legged kicking ergometry. Muscle biopsies were collected from the vastus lateralis muscle from both working legs, and blood samples were collected from one femoral artery and femoral vein before, during, and in recovery from exercise. We show that the exercise stimulus elicited a decrease in VEGF protein arteriovenous balance across the exercising leg (P = 0.007), and a ninefold elevation in skeletal muscle VEGF mRNA expression (P < 0.001). The changes in VEGF protein balance and mRNA content were most pronounced 1 h after the cessation of exercise. In conclusion, these findings demonstrate that submaximal exercise, suitable for humans with low CV fitness, induces a decrease in VEGF arteriovenous balance that is likely to be of clinical significance in promoting angiogenic effects.

Glutamine supplementation further enhances exercise-induced plasma IL-6.

Exercise stimulates the production and release of interleukin-6 (IL-6) from skeletal muscle. Glutamine is also synthesized in skeletal muscle and is involved in protein synthesis within this tissue. During exercise, plasma levels of glutamine decline, and this may affect the concentration of plasma IL-6 via a decrease in IL-6 synthesis and release from muscle. We hypothesized that glutamine supplementation would attenuate the exercise-induced decrease in plasma glutamine concentration and, thus, further enhance levels of plasma IL-6. Eight healthy men participated in a randomized, double-blind, crossover study in which they performed 2 h of cycle ergometry at 75% of peak O2 uptake. They received glutamine, glutamine-rich protein, or placebo supplementation at intervals during and 2 h after exercise. Exercise induced an 11-fold increase in plasma IL-6, which was further enhanced by glutamine (18-fold) and glutamine-rich protein (14-fold) supplementation, administered at doses that attenuated the exercise-induced decrease in plasma glutamine concentration.

A comparison of plasma glutamine concentration in athletes from different sports.

PURPOSES: The purposes of the current investigation were to compare resting plasma glutamine concentration in athletes from different sports and to determine the relationship between resting plasma glutamine concentration and dietary protein intake. METHODS: Resting plasma glutamine concentration was measured in five groups of eight distance runners, competitive swimmers, cyclists, powerlifters, and nonathletes. Dietary protein intake of each subject was measured (g.d-1 and g.kg-1.d-1). RESULTS: Plasma glutamine concentration was significantly different between sports (P = 0.000, ANOVA) with mean plasma glutamine concentration of cyclists significantly higher than in all other groups, and mean plasma glutamine concentration of powerlifters and swimmers significantly lower than in cyclists and nonathletes (P < 0.05, post hoc analysis). There was no significant relationship between plasma glutamine concentration and total dietary protein intake when expressed as g.d-1 (r = 0.11, P > 0.05); however, plasma glutamine concentration and dietary protein relative to body mass (g.kg-1.d-1) were significantly inversely correlated (r = -0.37, P = 0.007). CONCLUSIONS: These data suggest that resting plasma glutamine concentration may vary between sports, possibly due to metabolic demands of the different sports; dietary factors may also affect plasma glutamine concentration.