No abstract

A sthma is a chronic inflammatory disease which is accompanied by extensive changes in normal airway tissue architecture, termed remodeling (1, 2). Airway remodeling in asthma comprises epithelial dysfunction, hypertrophy of the mucus glands, subepithelial vascularization, and changes in extracellular matrix composition (2). In addition, airway smooth muscle (ASM) from people suffering with asthma exhibits enhanced proliferative (3) and migratory responses (4, 5), as well as increased secretion of a myriad of pro-inflammatory cytokines/ chemokines and growth factors (6). The mechanisms that underly the exaggerated function of ASM in asthma are unknown.Smooth muscle responses to diverse stimuli are controlled by changes in the concentration of free cytosolic Ca 2ϩ ([Ca 2ϩ ] i ). Elevation of [Ca 2ϩ ] i results from increased Ca 2ϩ influx across the plasma membrane following activation of Ca 2ϩ -permeable ion channels and the Na ϩ -Ca 2ϩ -exchanger (NCX, 3Na ϩ :1Ca 2ϩ ), and by release of stored Ca 2ϩ from the sarcoplasmic reticulum (SR), in turn triggered by inositol 1,4,5-triphosphate (IP 3 ) or ryanodine receptor (RyR) channels (7). Termination of the cytosolic Ca 2ϩ signal occurs by extracellular removal of cytosolic Ca 2ϩ by the NCX and by its rapid sequestration into SR stores by the sarco/endoplasmic reticulum Ca 2ϩ (SERCA) pump (7). Impaired replenishment of SR stores arising from reduced activity of the SERCA pump could impact on a wide range of Ca 2ϩ -dependent smooth muscle functions (8) and abnormal Ca 2ϩ handling by ASM has previously been proposed to be an important determinant of the airway hyperresponsiveness that is characteristically present in asthma (9, 10).There are 3 tissue-specific members of the mammalian SERCA family, SERCA1, SERCA2 and SERCA3, each encoded by a separate gene (ATP2A1, ATP2A2, and ATP2A3) (11), with SERCA2 being the most highly expressed in smooth muscle (12, 13). The function of the different isoforms of SERCA2 is similar (14). We have investigated if the secretory and hyperproliferative phenotype of ASM in asthma is associated with impaired SERCA isoform expression. Results SERCA2Expression. SERCA2 mRNA expression was reduced in ASM cells cultured from patients with moderate, but not mild asthma compared with cells derived from healthy subjects (P ϭ 0.04, Fig. 1A). Western immunoblot showed a single band for SERCA2 at the expected size (Ϸ110 kDa) in ASM lysates (Fig. 1). SERCA2 protein expression was correspondingly reduced in ASM cells from patients with moderate asthma (P ϭ 0.015, Fig. 1B). In contrast, IP 3 R1 mRNA and protein expression did not differ between asthmatics and controls ( Fig. 1 A and B), suggesting the change in SERCA2 was not the result of a reduction in total SR. Transcripts for SERCA1, and SERCA3 were not detected in ASM. Further experiments using SERCA2A, SERCA2B, and SERCA2C specific primers demonstrated that predominant isoform in ASM is SERCA2B with the other isoforms expressed at very low levels around the limit of detection. The pattern of ...

NCT00978315 (ClinicalTrials.gov).

Purpose:The aim of this study was to determine whether compression garments improve intermittent-sprint performance and aid performance or self-reported recovery from high-intensity efforts on consecutive days.Methods:Following familiarization, 14 male rugby players performed two randomized testing conditions (with or without garments) involving consecutive days of a simulated team sport exercise protocol, separated by 24 h of recovery within each condition and 2 weeks between conditions. Each day involved an 80-min high-intensity exercise circuit, with exercise performance determined by repeated 20-m sprints and peak power on a cart dynamometer (single-man scrum machine). Measures of nude mass, heart rate, skin and tympanic temperature, and blood lactate (La−) were recorded throughout each day; also, creatine kinase (CK) and muscle soreness were recorded each day and 48 h following exercise.Results:No differences (P = .20 to 0.40) were present between conditions on either day of the exercise protocol for repeated 20-m sprint efforts or peak power on a cart dynamometer. Heart rate, tympanic temperature, and body mass did not significantly differ between conditions; however, skin temperature was higher under the compression garments. Although no differences (P = .50) in La− or CK were present, participants felt reduced levels of perceived muscle soreness in the ensuing 48 h postexercise when wearing the garments (2.5 ± 1.7 vs 3.5 ± 2.1 for garment and control; P = .01).Conclusions:The use of compression garments did not improve or hamper simulated team-sport activity on consecutive days. Despite benefits of reduced self-reported muscle soreness when wearing garments during and following exercise each day, no improvements in performance or recovery were apparent.