Effects of Preoperative Short Term Use of Atorvastatin on Endothelial Progenitor Cells after Coronary Surgery: A Randomized, Controlled Trial

Objectives

We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell (EPC) count after on-pump coronary artery bypass surgery (CABG).

Methods

Between Feb-2010 and May-2010, we randomly assigned, in a placebo-controlled, double-blind study, 60 consecutive patients who underwent isolated, first-time CABG to receive either 14-day atorvastatin (40 mg/day) or placebo preoperatively. Urgent CABG and recent myocardial infarction were excluded. EPCs were quantified (cells/μl) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T₁), 6-hours (T₂), and on the 5th day postoperatively (T₃). Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery.

Results

There were no differences in baseline risk factors including cholesterol profiles, and EuroSCORES between the groups. The composite primary end-point, favored statin group with higher amount of circulating, early EPC count (cells/μl) at all time points compared with placebo (T₁, 2.30?±?0.02 versus 1.58?±?0.03, p?2, 5.00?±?0.06 versus 2.19?±?0.06, p?3, 3.03?±?0.08 versus 1.78?±?0.02, p?1, 0.8?±?0.1 versus 2.2?±?1.5, p?2, 72.9?±?3.2 versus 96.0?±?3.6, p?3, 4.3?±?1.2 versus 11.4?±?4.1, p?p?=?0.02).

Conclusions

Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels. (ClinicalTrials.gov number, NCT01096875)     

Combined caffeine and carbohydrate ingestion: effects on nocturnal sleep and exercise performance in athletes

Purpose

In athletes, caffeine use is common although its effects on sleep have not been widely studied. This randomised, double-blind, placebo-controlled crossover trial investigated the effects of late-afternoon caffeine and carbohydrate-electrolyte (CEB) co-ingestion on cycling performance and nocturnal sleep.

Methods

Six male cyclists/triathletes (age 27.5 ± 6.9 years) completed an afternoon training session (TS; cycling 80 min; 65 % VO_2max) followed by a 5 kJ kg^?1 cycling time trial (TT). Caffeine (split dose 2 × 3 mg kg^?1) or placebo was administered 1 h prior and 40 min into the TS. A 7.4 % CEB (3 ml kg^?1 every 15 min) was administered during the TS, followed 30 min after by a standardised evening meal. Participants retired at their usual bedtime and indices of sleep duration and quality were monitored via polysomnography. Data: mean ± SD.

Results

All participants performed better in the caffeine TT (caffeine 19.7 ± 3.3; placebo 20.5 ± 3.5 min; p = 0.006), while ratings of perceived exertion (caffeine 12.0 ± 0.6; placebo 12.9 ± 0.7; p = 0.004) and heart rate (caffeine 175 ± 6; placebo 167 ± 11 bpm; p = 0.085) were lower in the caffeine TS. Caffeine intake induced significant disruptions to a number of sleep indices including increased sleep onset latency (caffeine 51.1 ± 34.7; placebo 10.2 ± 4.2 min; p = 0.028) and decreased sleep efficiency (caffeine 76.1 ± 19.6; placebo 91.5 ± 4.2 %; p = 0.028), rapid eye movement sleep (caffeine 62.1 ± 19.6; placebo 85.8 ± 24.7 min; p = 0.028) and total sleep time (caffeine 391 ± 97; placebo 464 ± 49 min; p = 0.028).

Conclusions

This study supports a performance-enhancing effect of caffeine, although athletes (especially those using caffeine for late-afternoon/evening training and competition) should consider its deleterious effects on sleep.     

Aqueous extracts from dietary supplements influence the production of inflammatory cytokines in immortalized and primary T lymphocytes

Background

Congaplex^® and Immuplex^® are dietary supplements that have been traditionally used to support immune system function. The purpose of these experiments was to determine whether Congaplex^® and Immuplex^® affect immune function using primary and immortalized T lymphocytes.

Methods

Immortalized CEM and Jurkat T lymphocytes and primary peripheral mononuclear blood cells (PBMCs) were treated with the aqueous extracts from Congaplex^® and Immuplex^® to determine the effects of these products on cytokine production in activated T lymphocytes.

Results

Congaplex^® enhanced phytohemagglutinin/phorbol 12-myristate 13-acetate (PHA/PMA) stimulation of both CEM and Jurkat cells as measured by the production of cytokines, while Immuplex^® suppressed PHA/PMA-induced production of cytokines, with the exception of interleukin (IL)-8 which was enhanced by Immuplex^®. In vitro treatment of PBMCs from 10 healthy donors with Congaplex^® or Immuplex^® decreased PHA-stimulated production of interferon (IFN)-γ but increased the production of IL-13.

Conclusions

While the effects of Congaplex^® and Immuplex^® differed in these two models, these data demonstrate that the aqueous extracts from these two dietary supplements can affect the inflammatory response of T lymphocytes.     

Glucocorticoids improve high-intensity exercise performance in humans

Purpose

It was investigated whether oral dexamethasone (DEX) administration improves exercise performance by reducing the initial rate of muscle fatigue development during dynamic exercise.

Methods

Using a double-blinded placebo controlled randomized crossover design, subjects ingested either 2 × 2 mg of DEX or placebo for five consecutive days. Muscle function was investigated using one-legged kicking exercise and whole body performance was evaluated using a 20-m shuttle run and a 30-m sprint test.

Results

One-legged dynamic knee-extensor exercise time to exhaustion was 29 ± 35 % (mean ± SD) longer (P < 0.05) in DEX compared to Placebo. Likewise, total running distance in the shuttle run test was 19 ± 23 % longer (P < 0.05), whereas 30-m sprint performance was unaltered. During the initial 75 s of dynamic leg extensions, peak force and rate of force development determined from an electrically evoked twitch declined in a similar way in DEX and placebo. Similarly, the EMG root mean square was similar with DEX and placebo treatment.

Conclusion

Short-term dexamethasone administration increases high-intensity one-legged kicking time to exhaustion and 20-m shuttle run performance, although sprint ability and the initial loss of muscular force generating capacity are similar after DEX and placebo.     

The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal

Introduction

Many environmental and dietary influences can cause immune cells to produce biological mediators that increase airway inflammation. A high-fat meal (HFM) is one stimulus that increases airway inflammation in healthy individuals. Supplementation with omega-3 fatty acids can reduce inflammation systemically and may be beneficial to the airways.

Purpose

To determine if omega-3 fatty acid supplementation via fish oil would mitigate the airway inflammatory response induced by a single HFM.

Methods

Seventeen non-asthmatic men (22 ± 2 years.) were supplemented with 3,000 mg × day^?1 fish oil or a placebo for 3 weeks. Fractional exhaled nitric oxide (FE_NO; a marker of airway inflammation), impulse oscillometry (a measure of respiratory impedance), pulmonary function, and triglycerides were measured prior to and 2 h following a HFM.

Results

Following a HFM, triglycerides increased in both fish oil and placebo groups compared to pre-HFM (~59 and ~49 %, respectively, p < 0.05). The percent increase in FE_NO was greater in the placebo group compared to the fish oil group (25.7 ± 16.7 vs. ?1.99 ± 10.5 %, respectively, p < 0.05). A significant correlation was observed between blood triglycerides and FE_NO in the placebo group (r = 0.61; p < 0.05), but not the fish oil group (p = 0.21).

Conclusion

A single HFM increases airway inflammation and omega-3 fatty acid supplementation via fish oil protects against HFM associated changes in airway health.     

A Multicenter, Prospective, Open Label, Historically Controlled Clinical Trial to Evaluate Efficacy and Safety in Primary Immunodeficiency Diseases (PID) Patients of Flebogamma® 5% DIF, the Next Generation of Flebogamma®

Background

Flebogamma® 5% dual inactivation and filtration (DIF) is the next generation of Flebogamma®. Flebogamma® was first licensed in 1992. The new preparation features additional viral inactivation and removal steps to enhance safety margins.

Objective

The purpose of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma® 5% DIF for immunoglobulin replacement therapy in primary immunodeficiency diseases (PID).

Methods

Flebogamma® 5% DIF was administered at seven clinical sites to 46 subjects with well-defined primary immunodeficiency diseases at a dose of 300–600 mg/kg every 21–28 days for 12 months.

Results

The calculated serious bacterial infection rate was 0.021/subject/year. The incidence of adverse events considered potentially related to Flebogamma® 5% DIF during or within 72 h after completing an infusion was approximately 10%. The half-life in serum of the administered IgG was around 31 days.

Conclusions

Flebogamma® 5% DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated and maintains the profile of Flebogamma® 5% for the treatment of primary humoral immunodeficiency diseases.     

Efficacy, Pharmacokinetics, Safety, and Tolerability of Flebogamma® 10% DIF, a High-Purity Human Intravenous Immunoglobulin, in Primary Immunodeficiency

Background

Flebogamma® 10% DIF represents an evolution of intravenous immune globulin from the previous 5% product to be administered at higher rates and with smaller infusion volumes. Pathogen safety is enhanced by the combination of multiple methods with different mechanisms of action.

Objective

The objective of this study as to evaluate the efficacy, pharmacokinetics, and safety of Flebogamma® 10% DIF for immunoglobulin replacement therapy in primary immunodeficiency diseases (PIDD).

Methods

Flebogamma® 10% DIF was administered to 46 subjects with well-defined PIDD at a dose of 300–600 mg/kg every 21–28 days for 12 months.

Results

Serious bacterial infection rate was 0.025/subject/year. Half-life in serum of the administered IgG was approximately 35 days. No serious treatment-related adverse event (AE) occurred in any patient. Most of the potentially treatment-related AEs occurred during the infusion, accounting for 20% of the 601 infusions administered.

Conclusions

Flebogamma® 10% DIF is efficacious and safe, has adequate pharmacokinetic properties, and is well-tolerated for the treatment of PIDD.     

Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine

Background

There is increasing recognition that many of today's diseases are due to the "oxidative stress" that results from an imbalance between the formation and neutralization of reactive molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can be removed with antioxidants. The main objective of the present study was to evaluate the antioxidant activity of plants routinely used in the Unani system of medicine. Several plants were screened for radical scavenging activity, and the ten that showed promising results were selected for further evaluation.

Methods

Methanol (50%) extracts were prepared from ten Unani plants, namely Cleome icosandra, Rosa damascena, Cyperus scariosus, Gardenia gummifera, Abies pindrow, Valeriana wallichii, Holarrhena antidysenterica, Anacyclus pyrethrum, Asphodelus tenuifolius and Cyperus scariosus, and were used to determine their total phenolic, flavonoid and ascorbic acid contents, in vitro scavenging of DPPH^·, ABTS^·+, NO, ^·OH, O₂ ^.- and ONOO^-, and capacity to prevent oxidative DNA damage. Cytotoxic activity was also determined against the U937 cell line.

Results

IC₅₀ values for scavenging DPPH^·, ABTS^·+, NO, ^·OH, O₂ ^.- and ONOO^- were in the ranges 0.007 ± 0.0001 - 2.006 ± 0.002 mg/ml, 2.54 ± 0.04 - 156.94 ± 5.28 μg/ml, 152.23 ± 3.51 - 286.59 ± 3.89 μg/ml, 18.23 ± 0.03 - 50.13 ± 0.04 μg/ml, 28.85 ± 0.23 - 537.87 ± 93 μg/ml and 0.532 ± 0.015 - 3.39 ± 0.032 mg/ml, respectively. The total phenolic, flavonoid and ascorbic acid contents were in the ranges 62.89 ± 0.43 - 166.13 ± 0.56 mg gallic acid equivalent (GAE)/g extract, 38.89 ± 0.52 - 172.23 ± 0.08 mg quercetin equivalent (QEE)/g extract and 0.14 ± 0.09 - 0.98 ± 0.21 mg AA/g extract. The activities of the different plant extracts against oxidative DNA damage were in the range 0.13-1.60 μg/ml. Of the ten selected plant extracts studied here, seven - C. icosandra, R. damascena, C. scariosus, G. gummifera, A. pindrow, V. wallichii and H. antidysenterica - showed moderate antioxidant activity. Finally, potentially significant oxidative DNA damage preventive activity and antioxidant activity were noted in three plant extracts: C. icosandra, R. damascena and C. scariosus. These three plant extracts showed no cytotoxic activity against U937 cells.

Conclusions

The 50% methanolic extracts obtained from different plant parts contained significant amounts of polyphenols with superior antioxidant activity as evidenced by the scavenging of DPPH^·, ABTS^·+, NO, ^·OH, O₂ ^.- and ONOO^-. C. icosandra, R. damascena and C. scariosus showed significant potential for preventing oxidative DNA damage and radical scavenging activity, and the G. gummifera, A. pindrow, V. wallichii, H. antidysenterica, A. pyrethrum, A. tenuifolius and O. mascula extracts showed moderate activity. The extracts of C. icosandra, R. damascena and C. scariosus showed no cytotoxicity against U937 cells. In conclusion, these routinely used Unani plants, especially C. icosandra, R. damascena and C. scariosus, which are reported to have significant activity against several human ailments, could be exploited as potential sources of natural antioxidants for plant-based pharmaceutical industries.     

Changes in heart rate variability during the induction and decay of heat acclimation

Purpose

We evaluated the changes in core temperature, heart rate, and heart rate variability (HRV) during the induction and decay of heat acclimation.

Methods

Ten males (23 ± 3 years; 79.5 ± 3.5 kg; 15.2 ± 4.5 percent body fat; 51.13 ± 4.61 mLO²?kg^?1?min^?1 peak oxygen uptake) underwent a 14-day heat acclimation protocol comprising of 90-min cycling at ~50 % peak oxygen uptake at 40 °C and ~20 % relative humidity. Core temperature, heart rate, and 102 HRV measures were recorded during a heat tolerance test conducted at baseline (day 0) and at the end of the induction (day 14) and decay (day 28) phases.

Results

Heat acclimation resulted in significantly reduced core temperature [rectal (χ ² = 1298.14, p < 0.001); esophageal (χ ² = 1069.88, p < 0.001)] and heart rate (χ ² = 1230.17, p < 0.001). Following the decay phase, 26, 40, and 60 % of the heat acclimation-induced reductions in rectal temperature, esophageal temperature, and heart rate, respectively, were lost. Heat acclimation was accompanied by profound and broad changes in HRV: at the end of the induction phase, 75 of the 102 variability measures computed were significantly different (p < 0.001), compared to only 47 of the 102 at the end of the decay phase.

Conclusions

Heat acclimation is accompanied by reduced core temperature, significant bradycardia, and marked alterations in HRV, which we interpret as being related to vagal dominance. The observed changes in core temperature persist for at least 2 weeks of non-exposure to heat, while the changes in heart rate and HRV decay faster and are only partly evident after 2 weeks of non-exposure to heat.     

A retrospective comparison of the location and diameter of the inferior alveolar canal at the mental foramen and length of the anterior loop between American and Taiwanese cohorts using CBCT

Purpose

The aim was to retrospectively compare the measurements of the location and size of the inferior alveolar canal at the mental foramen and the length of the anterior loop between two cohorts of Americans and Taiwanese using cone-beam computed tomography (CBCT).

Methods

CBCT was performed with an I-CAT^® Cone-Beam 3D Dental Imaging System and reconstructed into multiple-plane views to measure two populations.

Results

There was no statistically significant difference (P = 0.2681) in the distance from the mental foramen to the inferior border of the mandible (mandibular border height) between Americans (9.84 ± 2.01 mm) and Taiwanese (10.13 ± 1.66 mm). No significant difference was found (p = 0.1161) in the inferior alveolar canal diameter between these two cohorts (2.26 ± 0.67 and 2.13 ± 0.47 mm, respectively). However, the anterior loop length of Taiwanese (7.61 ± 1.81 mm) was significantly longer than that of Americans (6.22 ± 1.68 mm) (P < 0.0001).

Conclusion

Our study indicated that (1) the location of mental foramen of Americans was closer to the inferior border of the mandible than Taiwanese; (2) the diameter of the inferior alveolar canal of Americans was larger than Taiwanese; (3) the anterior loop of Taiwanese was longer than Americans. These differences may be, at least partly, due to the racial influence and this information may possess potential valuable clinical relevance.     

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

Purpose

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D₃ in healthy young males upon skeletal muscle function.

Methods

Participants (n = 29) received an oral dose of 10,000 IU day^?1 vitamin D₃ (VITD) or a visually identical placebo (PLB) for 3 months. Serum 25[OH]D and intact parathyroid hormone (iPTH) were measured at baseline and at week 4, 8 and 12. Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12.

Results

Baseline mean total serum 25[OH]D was 40 ± 17 and 41 ± 20 nmol L^?1 for PLB and VITD, respectively. VITD showed a significant improvement in total 25[OH]D at week 4 (150 ± 31 nmol L^?1) that remained elevated throughout the trial (P < 0.005). Contrastingly, PLB showed a significant decrease in 25[OH]D at week 12 (25 ± 15 nmol L^?1) compared with baseline. Despite marked increases in total serum 25[OH]D in VITD and a decrease in PLB, there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group (P > 0.05).

Conclusions

Elevating total serum 25[OH]D to concentrations > 120 nmol L^?1 has no effect on skeletal muscle function. We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency (<12.5 nmol L^?1).     

Real-time PCR complements immunohistochemistry in the determination of HER-2/neu status in breast cancer

Background

The clinical benefit of determining the status of HER-2/neu amplification in breast cancer patients is well accepted. Although immunohistochemistry (IHC) is the most frequently used method to assess the over-expression of HER-2 protein, fluorescent in-situ hybridization (FISH) is recognized as the "gold standard" for the determining of HER-2/neu status. The greatest discordance between the two methods occurs among breast tumors that receive an indeterminate IHC score of 2+. More recently, a real-time polymerase chain reaction (PCR) assay using the LightCycler^® has been developed for quantifying HER-2/neu gene amplification. In this study, we evaluated the sensitivity and specificity of a commercially available LightCycler assay as it compares to FISH. To determine whether this assay provides an accurate alternative for the determination of HER-2/neu status, we focused primarily on tumors that were deemed indeterminate or borderline status by IHC.

Methods

Thirty-nine breast tumors receiving an IHC score of 2+ were evaluated by both FISH and LightCycler^® technologies in order to determine whether quantitative real-time PCR provides an accurate alternative for the determination of HER-2/neu status.

Results

We found a high concordance (92%) between FISH and real-time PCR results. We also observed that 10% of these tumors were positive for gene amplification by both FISH and real-time PCR.

Conclusion

The data show that the results obtained for the gene amplification of HER-2/neu by real-time PCR on the LightCycler^® instrument is comparable to results obtained by FISH. These results therefore suggest that real-time PCR analysis, using the LightCycler^®, is a viable alternative to FISH for reassessing breast tumors which receive an IHC score of 2+, and that a combined IHC and real-time PCR approach for the determination of HER-2 status in breast cancer patients may be an effective and efficient strategy.     

An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain

Background

Opioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS^® hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective of this study (DO-118X) was to characterise the pain control achieved with long-term repeated dosing of OROS^® hydromorphone in patients with chronic cancer pain.

Methods

In this multicentre, phase III, open-label, single treatment, 1-year extension study, OROS^® hydromorphone was administered to 68 patients with moderate-to-severe chronic cancer pain, who had successfully completed a short-term equivalence study, and whose pain was controlled with a stable dose of medication (≥ 8 mg OROS^® hydromorphone or equivalent controlled-release morphine). Patients were started on the dose of OROS^® hydromorphone equivalent to the opioid dose on which they achieved dose-stable pain control in the equivalence study; dose adjustments were made as necessary and breakthrough pain medication was permitted. Efficacy was assessed with the Brief Pain Inventory (BPI) and patient and investigator global evaluations of treatment effectiveness. No formal statistical analysis was done.

Results

The mean (standard deviation) duration of exposure to study medication was 139 (129.9) days and the mean (standard deviation) average daily consumption of OROS^® hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a mild to moderate severity throughout the study; however, BPI scores for pain at its worst, pain at its least, pain on average, pain right now, and pain relief were slightly worsened at end point compared with baseline. Mean BPI pain interference with daily activities and patient and investigator global evaluation scores also remained generally stable. Treatment effectiveness was rated as fair to good throughout the study. The most frequently reported adverse events were nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15, 22.1%).

Conclusion

The results of this extension study suggest that long-term repeated dosing with once-daily OROS^® hydromorphone can be beneficial in the continuing management of persistent, moderate-to-severe cancer pain.     

Functional expression of a single-chain antibody to ErbB-2 in plants and cell-free systems

Background

Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory growth factor, granulocyte monocyte stimulating factor (GM-CSF, Leukine^®) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-γ1b, Actimmune^®) has been developed. The pre- and post-chemotherapy design is based upon known in vivo kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin^®) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC).

Methods

We studied hematopoietic and immunologic effects of GM-CSF and rIFN-γ1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 μg/day) for 7 days plus subcutaneous rIFN-γ1b (100 μg) on days 5 and 7, before and after intravenous carboplatin (area under the curve of 5). We performed standard hematologic assessment and monitored monocyte (MO), dendritic cell, major cell subset counts, and antibody-dependent cell-mediated cytotoxicity (ADCC) against a Her2neu⁺ tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels.

Results

Our analysis comprised only the first 3 months of treatment in the initial 25 patients. Relative to pretreatment baseline values, white blood cell, neutrophil, MO, and eosinophil counts increased (P ≤.001 for each); the proportion of platelets increased 9 days after the second (P ≤.002) and third (P ≤.04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14⁺CXCR3⁺ increased (P ≤.04 for each); plasma levels of the proangiogenic interleukins 1α, 6, and 8 were lower (P ≤.03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 (P =.007); and GM-CSF was increased in plasma after GM-CSF administration (P ≤.04). Quality of life measurements were reduced during the GM-CSF/IFN-γ1b cycle while recovering at pre-chemotherapy baseline for FACT-G scores only.

Conclusion

A novel regimen of GM-CSF plus IFN-γ1b administered to 25 EOC patients receiving carboplatin increased myeloid cells, platelets and total activated MO populations during the initial 3 months; however, ADCC responses were not consistently enhanced during this period.     

Ramp-incremented and RPE-clamped test protocols elicit similar VO2max values in trained cyclists

Purpose

The present study compared the efficacy of ramp incremented and ratings of perceived exertion (RPE)-clamped test protocols for eliciting maximal oxygen uptake (VO_2max).

Methods

Sixteen trained cyclists (age 34 ± 7 years) performed a ramp-incremented protocol and an RPE-clamped protocol 1 week apart in a randomized, counterbalanced order. The RPE-clamped protocol consisted of five, 2-min stages where subjects self-selected work rate and pedal cadence to maintain the prescribed RPE. After completing both test protocols subjects were asked which they preferred.

Results

The mean ± SD test time of 568 ± 72 s in the ramp protocol was not significantly different to the 600 ± 0 s in the RPE-clamped protocol (mean difference = 32 s; p = 0.09), or was the VO_2max of 3.86 ± 0.73 L min^?1 in the ramp protocol significantly different to the 3.87 ± 0.72 L min^?1 in the RPE-clamped protocol (mean difference = 0.002 L min^?1; p = 0.97). Furthermore, no significant differences were observed for peak power output (p = 0.21), maximal minute ventilation (p = 0.97), maximal respiratory exchange ratio (p = 0.09), maximal heart rate (p = 0.51), and post-test blood lactate concentration (p = 0.58). The VO_2max attained in the preferred protocol was significantly higher than the non-preferred protocol (mean difference = 0.14 L min^?1; p = 0.03).

Conclusion

The RPE-clamped test protocol was as effective as the ramp-incremented protocol for eliciting VO_2max and could be considered as a valid alternative protocol, particularly where a fixed test duration is desirable.     

Operating lung volumes are affected by exercise mode but not trunk and hip angle during maximal exercise

Introduction

Despite VO_2peak being, generally, greater while running compared to cycling, ventilation (V _E) during maximal exercise is less while running compared to cycling. Differences in operating lung volumes (OLV) between maximal running and cycling could be one explanation for previously observed differences in V _E and this could be due to differences in body position e.g., trunk/hip angle during exercise.

Purpose

We asked whether OLV differed between maximal running and cycling and if this difference was due to trunk/hip angle during exercise.

Methods

Eighteen men performed three graded maximal exercise tests; one while running, one while cycling in the drop position (i.e., extreme hip flexion), and one while cycling upright (i.e., seated with thorax upright). Resting flow-volume characteristics were measured in each body position to be used during exercise. Tidal flow-volume loops were measured throughout the exercise.

Results

V _E during maximal running (148.8 ± 18.9 L min^?1) tended to be lower than during cycling in the drop position (158.5 ± 24.7 L min^?1; p = 0.07) and in the upright position (158.5 ± 23.7 L min^?1; p = 0.06). End-inspiratory and end-expiratory lung volumes (EILV, EELV) were significantly larger during drop cycling compared to running (87.1 ± 4.1 and 35.8 ± 6.2 vs. 83.9 ± 6.0 and 33.0 ± 5.7 % FVC), but only EILV was larger during upright cycling compared to running (88.2 ± 3.5 % FVC). OLV and V _E did not differ between cycling positions.

Conclusion

Since OLV are altered by exercise mode, but cycling position did not have a significant impact on OLV, we conclude that trunk/hip angle is likely not the primary factor determining OLV during maximal exercise.     

Energy expenditure of extreme competitive mountaineering skiing

Purpose

Multi-hour ski mountaineering energy balance may be negative and intake below recommendations.

Methods

Athletes on the ‘Patrouille des Glaciers’ racecourses (17 on course Z, 27 km, +2,113 m; 11 on course A, 26 km, +1,881 m) volunteered. Pre-race measurements included body mass, stature, VO_2max, and heart rate (HR) vs VO₂ at simulated altitude; race measurements HR, altitude, incline, location, and food and drink intake (A). Energy expenditure (EE) was calculated from altitude corrected HR derived VO₂.

Results

Race time was 5 h 7 min ± 44 min (mean ± SD, Z) and 5 h 51 min ± 53 min (A). Subjects spent 19.2 ± 3.2 MJ (Z), respectively, 22.6 ± 2.9 MJ (A) during the race. Energy deficit was ?15.5 ± 3.9 MJ (A); intake covered 20 ± 7 % (A). Overall energy cost of locomotion (EC) was 9.9 ± 1.3 J m^?1 kg^?1 (Z), 8.0 ± 1.0 J m^?1 kg^?1 (A). Uphill EC was 11.7 ± 1 J m^?1 kg^?1 (Z, 13 % slope) and 15.7 ± 2.3 J m^?1 kg^?1 (A, 19 % slope). Race A subjects lost ?1.5 ± 1.1 kg, indicating near euhydration. Age, body mass, gear mass, VO_2max and EC were significantly correlated with performance; energy deficit was not.

Conclusions

Energy expenditure and energy deficit of a multi-hour ski mountaineering race are very high and energy intake is below recommendations.     

Pain sensitivity is normalized after a repeated bout of eccentric exercise

Purpose

The purpose of this study was to investigate the effect of repeated bouts of eccentric exercise on the nociceptive withdrawal reflex (NWR) threshold, a measure of sensitivity in the spinal nociceptive system.

Methods

Sixteen healthy students (age 25.7 ± 0.6 years, BMI 24.8 ± 1 kg m^?2) participated in this randomized, controlled, crossover study. Two identical bouts of high-intensity eccentric exercises were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks apart the exercise sessions. Pressure pain thresholds (PPT) and the NWR threshold were recorded before, immediately after, and 1 day after both bouts of exercise.

Results

Pressure pain thresholds decreased significantly at two of the muscle belly sites on the day after initial bout compared with baseline. NWR threshold decreased by 25 ± 4 % immediately after initial bout and by 30 ± 5 % the next day (p < 0.05) as an indication of generalized pain hypersensitivity. On the contrary, no changes were found in both pain thresholds after second bout of eccentric exercise indicating that both localized and generalized pain sensitivity were normalized.

Conclusion

In conclusion, this study for the first time documented that an initial bout of unaccustomed high-intensity eccentric exercise, which results in muscle soreness can induce central sensitization. A repeated bout of exercise, however, facilitates inherent protective spinal mechanisms against the development of muscle soreness.     

Long-term treatment with methanandamide attenuates LPS-induced periodontitis in rats

Objective

Evidence exists of the anti-inflammatory and immunological properties of endocannabinoids in various tissues; the aim of the present study was therefore to assess the effect of long-term treatment with the synthetic cannabinoid methanandamide (Meth-AEA) on the progression of periodontitis in rats.

Materials and methods

Periodontitis was induced by injecting LPS (1?mg/ml) into the gingiva around the neck of the first upper and lower molars, and into the inter-dental space between the first and second molars. This protocol was repeated for 6?weeks on days 1, 3, and 5 of each week.

Results

Long-term treatment with topical Meth-AEA (500?ng/ml), applied daily to gingival tissue of rats induced with periodontitis, significantly diminished the alveolar bone loss, measured as the distance between the cemento-enamel junction and the alveolar crest, in both maxillary and mandibular first molars, compared to rats without treatment (P?P?P?Conclusion These results demonstrate the beneficial effects of treatment with Meth-AEA on gingival tissue of rats with periodontitis.     

Gradient compression garments protect against orthostatic intolerance during recovery from bed rest

Introduction

Abdomen-high, lower body graded compression garments (GCGs) may represent the next-generation of orthostatic intolerance protection with applications for exploration missions and commercial space flight.

Purpose

To evaluate the efficacy of the GCG to prevent orthostatic intolerance after a 14-day 6° head-down tilt bed rest (BR) and to determine whether wearing thigh-high compression garments impairs recovery from BR.

Methods

Sixteen (12 M, 4 F) subjects participated in a 15-min 80° head-up tilt test 5 day before BR (BR-5), on the last morning of BR (BR+0), and on day 1 (BR+1) and 3 after BR (BR+3). No subjects wore the GCG on BR-5, and all subjects wore the GCG during testing on BR+0. Control subjects (n = 8) wore the GCG only through testing on BR+0. Treatment subjects (n = 8) wore the GCG on BR+0 and thigh-high garments on BR+1 and BR+2.

Results

No subjects were presyncopal during tilt on BR+0 while wearing the GCG. Despite lower plasma volume index (BR-5: 1.52 ± 0.06, BR+0: 1.32 ± 0.05 l/m²), the tilt-induced increase in heart rate (ΔHR, 17 ± 2 bpm) and decrease in stroke volume (ΔSV, ?28 ± 3 ml) on BR+0 were less than on BR-5 (24 ± 2 bpm, ?43 ± 4 ml). On BR+1 ΔHR in the control group (33 ± 4 bpm) was higher than in the treatment group (23 ± 2 bpm) but there were no group differences on BR+3.

Conclusions

Wearing the GCG prevented the orthostatic intolerance that is normally present after BR. Thigh-high garments provided protection after BR, and wearing these garments did not impair recovery.